Projects summaries

This project aims to refine the methods for calculating genetic risk scores. These scores are used in precision medicine to identify genetic risk factors associated with common diseases.

This project consists of studying the effects of different demographic phenomena on the genetics of a population. Genetic and genealogical data will be linked to better explain regional founder effects. The Quebec founder effect(s) will be compared with other known global founder populations. Certain hereditary diseases that are rare but more frequent in Saguenay (DM1, ARSACS) will be studied using data from CARTaGENE and genealogies from BALSAC, a population database gathering genealogies from the entire province of Quebec since the beginning of the colony. The expected results will increase knowledge on the genetic consequences related to founder effects and will allow for a better understanding of the genetic structure of populations. This will be useful to describe the distribution of inherited diseases and to target subpopulations for which disease-associated mutations are more frequent.

Inherited heart disease is a major cause of sudden death in apparently healthy young people. In recent years, we have been offering genetic tests (blood test) to identify the cause of diseases at the gene level. This allows early identification of family members at risk of death and thus the introduction of effective preventive measures (medication or intervention). The interpretation of the results of genetic analyses in our French Canadian population is limited by the absence of specific genetic data in the general population of Quebec. In this study, we will use genetic data from the CARTaGENE cohort to compare them to genetic data from patients with hereditary heart diseases. This will help to better interpret data from genetic analyses and thus allow clinicians to better counsel and treat family members of people with inherited heart diseases.

The objective of this project is to provide an overview of the CARTaGENE cohort and to present to the scientific community the possibilities offered by the genomic data available. The objective is to better understand genetic variability in Quebec. The project will focus in particular on the identification of genetic variants conferring risks of developing certain diseases, the study of their geographical distribution and the development of computer tools for researchers.

The main objective of this study is to use CARTaGENE data to determine the carrier rate in Quebec of certain genetic conditions that are more frequent in the French Canadian population.

Lyme disease (LD) is on the rise in Quebec and Canada and the population is increasingly concerned about exposure to ticks carrying Borrelia burgdorferi. Effective diagnosis and treatment of LD depends on our ability to recognize its symptoms. The improvement of current tests and the search for new biomarkers are a priority for public health authorities. A simplified procedure would facilitate the interpretation of results and improve sensitivity during the early stages of infection. We propose to develop a rapid carbohydrate antibody test for the detection of LD. Our long-term goal is to develop a rapid and robust analytical method for the detection of B. burgdorferi antibodies and provide patients with access to a diagnostic test at the early stage of infection.

Primary Ciliary Dyskinesia (PCD) is a rare inherited respiratory disease involving dysfunction of motile cilia that line the ears, sinuses, and lower airways.  Diagnosis of this disease is often difficult, as no single test can accurately diagnose all forms of PCD since there are over 50 different genes causing PCD, and all affect the structure of cilia in different fashions. Recently, variants in a rare PCD gene HYDIN have been discovered in French-Canadians as a cause of PCD. One specific HYDIN variant may account for a significant portion of PCD in Quebec. We are working with CARTaGENE to investigate how common HYDIN variants may account for PCD in the Quebec population, and if this gene is commonly found in French-Canadian PCD patients, then the diagnostic test of choice in this rare disease would change to genetic analysis in Quebec.

The mission of the Canada Excellence Research Chair (CERC) in Genomic Medicine is to use large-scale human genomics to improve the discovery and development of new therapeutics in Canada and worldwide. Our team is leading a multitude of projects to demonstrate the value of genomics in identifying and validating drug targets (https://www.genomic-medicine-cerc.online/) using a variety of next-generation sequencing and omics technologies. This project's overall aim is to combine analyses from large-scale genetic studies of rare and complex diseases and publically available health data to propel the growth of genetically-driven therapeutics.

In this project, we will extract information on a wide range of traits measured by CARTaGENE and combine this with genetic data we have in hand for complex traits ranging from eye disease to cancer. We will use these data to identify new genes, which influence a person’s risk of disease. We will also use the identified genes to construct predictors of future disease risk. Since CARTaGENE collects data on family history, we will explore how genetic data can be combined with family history information to generate more accurate estimates of disease risk. Our work on deriving more accurate predictions of disease risk will enable us to stratify an individual’s disease risk, enabling personalized disease prediction and precision prevention.

Household air pollution (HAP) attributed to wood use is a potential environmental risk factor for lung cancer, to which ~2.5 billion people worldwide are exposed. Known lung cancer risk factors (i.e., environmental tobacco smoke, outdoor air pollution, family history) do not fully account for the disease burden. We will leverage our global consortium of prospective studies (HAPCO: Household Air Pollution Cohorts), to, for the first time, accurately quantify the relative risk of lung cancer mortality associated with wood use. Furthermore, we will measure the potential reduction in lung cancer mortality if HAP is eliminated or reduced while adjusting for known and suspected lung carcinogens. Our robust harmonization of HAP data will also provide the unique opportunity to determine the relative and absolute risks associated with HAP exposures for cancers other than lung cancer.

This project aims to use CARTaGENE as a control cohort in a study on susceptibility to the virus that has caused the COVID-19 pandemic. We will combine this dataset with others from around Quebec to search for risk factors for both infection to the virus and for developing severe COVID-19 disease. The risk factors we investigate will be both genetic and non-genetic, for instance body mass index and medical history. The data from CARTaGENE will be particularly important because it is the only resource we will use that is representative of the population of Quebec as a whole. Using it will allow us to choose the most appropriate group of people to compare to those who were infected with the virus and those who were severely ill from the virus in order to see what risk factors occur more often in these people in contrast to the general population of Quebec.

Menopause is a critical reproductive event and earlier age at menopause increases a woman’s risk of cardiovascular diseases, subfertility, and early death. The timing of menopause can be influenced by environmental chemicals that disrupt hormones, such as perfluoroalkyl substances (PFAS). Canadians are routinely exposed to PFAS, which are used in a wide range of consumer products for their water and stain-repellent properties. In this project, we propose to examine the association between exposure to PFAS and the timing of menopause.

Heart diseases and neurodegenerative diseases affect millions of women and men in Canada. In many ways, they affect women differently than men. Predicting who is at high risk is critical for improved prevention, diagnosis and treatment. However, given current knowledge and the differences between women and men, women are often receiving an inaccurate diagnosis and inappropriate treatments. The researcher proposes to apply artificial intelligence methods to several large cohorts using detailed data (genetic, clinical and others) to create prediction models that are tailored to differences between the sexes. The goal of these efforts is to increase knowledge and improve the cardiovascular and neurological health for Canadians in general, and women in particular.

In people at high risk of heart disease, the best prevention strategy is based on improving lifestyle habits combined with the use of medication. Depending on the health of these individuals, the drugs will target cholesterol, blood pressure, or blood sugar levels. However, several studies suggest that starting the medication discourages people from making lifestyle changes. The effectiveness of the drugs is then reduced, which often leads to increased doses. This research project aims to study the relationship between lifestyle habits and medication use in the prevention of heart disease in the Quebec population. This project will help develop knowledge transfer approaches for both patients and healthcare professionals aimed at promoting healthy lifestyles and adherence to pharmacological treatment in the prevention of heart disease.

In the context of the COVID-19 pandemic in Quebec, assessing the key determinants of COVID-19 infection together with monitoring of the antibody levels following the spring 2020 epidemic peak is critically needed to help public health policies. It will help to understand risk factors for infection and severity of the disease as well as the socioeconomic impact on the community. This information will provide guidance for public health measures for potential futur waves of disease in the coming months.

In this project, we propose to analyze the clinical, epidemiological and socio-economic characteristics associated with the COVID-19 pandemic using an online questionnaire. We also propose to perform a prospective antibody surveillance study with repeated measures of SARS-CoV-2 antibody in CARTaGENE participants. This unprecedented characterization of the evolution of the COVID-19 infection will prove vital in decision-making about immunization and protection strategies.

Epilepsy affects about 3% of people. It is characterized by great genetic heterogeneity, involving hundreds of genes. The recent emergence of new sequencing technologies now allows to harness the full power of genomic sequencing for research in patients with epilepsy. However, even with an increasing number of genetic associations, the vast majority of cases of epilepsy remains unexplained at the genetic level. We believe this is because most genetic studies in epilepsy have focused on coding regions, leaving the vast majority of the genome (> 98%) unexplored. The objective of this project is to study the non-coding part of the genome of epilepsy patients. We propose to use the population structure to identify the non-coding genomic regions potentially associated with the disease. We expect to increase the number of epilepsy patients for whom we can find a genetic cause for their disease. This will allow us to better understand the genetic mechanisms underlying the disease. In addition, these findings could also shed light on better management and treatment of epilepsy.

Heterozygous familial hypercholesterolemia (HF) is a genetic disease manifested by very high blood cholesterol levels and the early development of cardiovascular diseases. HF affects about one in 100 people in the French-Canadian population, making it the most common genetic cardiovascular disease in Quebec.

Treatment for HF aims to normalize blood cholesterol levels. However, our understanding of the cardioprotective potential of healthy lifestyles (ie, eating a healthy diet, being physically active, drinking moderately, not smoking, getting enough sleep) in HF remains very limited. In the age of precision medicine, characterizing the influence of lifestyle habits in individuals with HF is essential to better guide the treatment of this disease. In this study, we will assess how adopting a healthy lifestyle influences the cardiovascular health of individuals with HF.

Significant investment has been placed in the identification of genetic risk factors for common diseases. Yet, outside of family history, genetic risk is almost never included in routine clinical risk assessments. The goal of this project is to develop artificial intelligence algorithms for the integration of genetic and traditional risk factors into comprehensive disease risk prediction.

The project ARCHI is a pilot of the PRECINOMICS project, which aims to demonstrate the feasibility of building an informatics data platform for the integration of health and genomics data of diverse sources to conduct precision medicine research in a secure environment. To demonstrate the feasibility of the developed pilot platform, a research project will be conducted using CARTaGENE genomic and clinical research data to study risk factors for cancer and cardiovascular disease.

Radon gas is now a well-known cancer risk factor for humans. However, our understanding of the mechanistic basis of this remains limited. This study will look into how radon gas can affect blood and if indicators of exposure, known as biomarkers, can be identified. Geographic mapping will be leveraged to help identify participants living in high and low radon risk zones. Blood samples will then be analyzed to identify associations to radon gas exposure. The outcomes of this work will provide an understanding of what types of biomolecules are released into the blood when individuals are living in high radon areas.

Lung cancer is the first cause of cancer-related death. Recent studies have achieved an important step in the understanding of the genes involve in lung cancer development. Although encouraging, these new discoveries do not directly lead to better management and treatment of afflicted patients. To do so, additional steps are required to identify the molecular mechanisms by which the newly identified genetic markers cause lung cancer. The goal of this research project is to find susceptibility genes and molecular mechanisms of lung cancer. The identification of lung cancer genes is currently an essential step to improve prognostic following surgery, to develop early detection tests, to custom-tailor future medical treatment, and to find new drug targets.

Psychiatric disorders such as bipolar disorder and Attention-Deficit Hyperactivity Disorder (ADHD) affect many individuals across the world. Genetic studies have demonstrated that these psychiatric disorders implicate numerous genes. Furthermore, a type of genetic studies called sequencing studies, have identified several rare variants associated with psychiatric disorders. Here, the research team seeks to characterize the effects of rare variants and genetic risk of psychiatric disorders on patients and healthy individuals. Additionally, the team aim to characterize how genetic risk associates with traits and behaviours. The team of Dr. Rouleau has been studying psychiatric disorders for over 20 years, with strong focuses on autism, bipolar disorder, and schizophrenia.

Hair and eye color (pigmentation) variation are primarily determined by our genes, and the environment has barely any impact. Pigmentation is primarily influenced by two types of melanin: eumelanin, which is a brown/black pigment, and pheomelanin, which is a red/yellow pigment. People who have ancestors in Europe have a high diversity in hair and eye color. The research team’s main goal is to find new genetic variants that determine hair and eye color variation in European populations. This can be done by comparing the self-reported hair and eye color of the participants of the Canadian Partnership for Tomorrow Project with their respective genomic variants. This study will provide novel insights about the genetic basis of hair and eye color, and is also of biomedical relevance, given the links that have been described between genetic variants associated with pigmentary traits and different forms of skin cancer.

Diseases transmitted by viruses, bacteria, parasites, prions or others, which are transmitted naturally between animals and humans, are called zoonoses. In a context of climate change, some zoonoses will be a growing public health issue. Currently, there is no clear picture of zoonotic diseases that are considered priorities in the general population and among workers. This project aims to respond to these shortcomings by proposing to conduct an exploratory study of priority zoonotic cases in Quebec among participants of the CARTaGENE cohort. The project is in two parts: the first part of the project aim to identify the number of priority zoonotic cases among CARTaGENE participants based on medical diagnoses; the second part will allow to identify different risk factors and more vulnerable population subgroups, and to better understand the clinical cases. The knowledge developed in this project will be useful for the various public health organizations, because they will help to better understand the portrait of these cases of prioritized zoonoses in adults to ultimately better guide the preventive interventions of public health authorities.

Essential tremor (ET) is a neurological disorder that causes a rhythmic shaking of several body parts during voluntary movements. ET is the most common movement disorder and genetic studies indicate that ET is inherited in 50-70% of cases. Genome-wide association studies (GWAS) identify risk factors associated with disorders by establishing specific genetic variations that are more frequent in individuals with a disorder than those without it; this point to genes that contribute to the risk of developing the disorder.

Here, the research team seeks to combine cohorts with CARTaGENE using new cases to further understand the genetics of ET. By understanding ET-associated common genetic variants they can be further biologically characterized to help identify potential therapeutical treatments in the future.

The goal of this proposal is to improve our understanding of the genetic diversity and spatial distribution of ancestry of the population of Quebec. This population has a rich heritage deriving ancestry from around the world. Indigenous peoples and immigrants from France and the United Kingdom provided a high proportion of the current genetic makeup of the population. The distribution of ancestral contributions varies across the Saint-Lawrence River valley and across Quebec as a result of a series of founder events and other historical events. We will use statistical analyses on the CARTaGENE data to learn more about population demography and other fine-scale patterns of genetic relatedness in the population of Quebec.

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Predicting breast cancer occurrence remains important, as it is still the most frequently diagnosed type of cancer and the second cause of death by cancer among French-Canadian women (Canadian Cancer Statistics 2017). Models can be used to calculate the risk of having cancer, one of the most popular being the Breast Cancer Risk Assessment Tool (BCRAT), developed in the United States. A common problem with these predicting models is their accuracy in other populations (countries or ethnicities). Many studies assessed or updated the BCRAT to adapt it to new countries (American, European, Asian, Oceanian). However, studies using the BCRAT in the Canadian population are limited and no previous study validated the BCRAT in the Quebec population.

Nowadays, genetic information can be used to predict the risk of developing breast cancer. These models could be used to improve prediction. Again, there is a lack of evaluation of these tools for the Quebec population.

The aim of this study is to assess and validate the BCRAT model with or without genetic data in the Quebec population.  Other prediction risk scores will also be assessed for other cancers (e.g. prostate, colon, lung).

The neurotensin hormone is secreted in various parts of the central nervous system and the digestive system. Neurotensin activates receptors localized in cells of the central nervous system, but also in those of the intestines. This activation is involved in several disorders of the central nervous system (schizophrenia, drug addiction, Parkinson's, pain, blood pressure control, eating disorders), as well as in inflammatory bowel diseases and even some cancers. The prevalence of some of these disorders is greater in people who carry genetic variants in neurotensin receptors. As part of this project, we want to collect data on CARTaGENE participants who carry a specific genetic variant in a receptor called NST1. Our study will provide a better understanding of the molecular mechanisms underlying certain neurotensin-associated diseases.

Cardiovascular diseases are an increasing burden in Canada and are associated with poor quality of life. To understand how our own individual combination of genetics, lifestyle and the environment can affect cardiovascular diseases or health, it is essential to develop holistic study approaches. This project will use advanced techniques in the detection of subtle changes to the heart and in the identification of factors that are associated with cardiovascular health. More specifically, we will use artificial intelligence to detect heart image features that reflect markers for future disease. Artificial intelligence will also be used to better understand the relationship of such features with genetics, lifestyle and environment. The aim is the development of individual health plans (including physical activity, nutrition, and other factors) that could be much more efficient than general lifestyle recommendations. This will ultimately result in a truly personalized approach to the prevention of cardiovascular disease.

Metabolic risk factors (e.g. high blood pressure, excess fat around the waist, low level of good cholesterol) are severe global health issues that are increasing in frequency. Several studies have established an association between metabolic risk factors and certain types of cancer. There is increasing evidence that depression is associated with the overall occurrence risk of cancer. Depression is also associated with metabolic risk factors, and having both conditions might increase the risk of developing cancer. The primary objective of the proposed study is to investigate the associations between metabolic risk factor, depression and incidence of cancer. A greater understanding of theses interactions can ultimately lead to increased accuracy in identifying groups at high risk of cancer and thus better inform preventative care and treatment.

Certain diseases observed in the elderly have been associated with aging of human cells, especially immune system cells. On the other hand, some people develop diseases associated with aging at a very young age: this phenomenon is called premature aging. The purpose of this study is to improve knowledge about blood markers of natural and premature aging in order to follow up and understand the diseases caused by it. The primary goal is to validate a new premature aging blood marker called TREC. We will also test a series of 40 blood markers called cytokines. These cytokines are molecules that cause chronic inflammation and are also potential markers of aging. To answer these questions, we will use biological specimens of the CARTaGENE cohort.

In Canada, lung cancer is the most deadly cancer in among men and women. This research is interested in epigenetics, changes in DNA that controls cellular function and in the development of lung cancer. DNA methylation is a common element of epigenetics, which simply describes a modified form of DNA typically associated with regulating the expression of a gene and/or the stability of our chromosomes. It is thought that many lifestyle and environmental factors can change methylation patterns and that altered levels of DNA methylation is an early event that occurs in the development of cancer. This study proposes to examine the relationships between lifestyle and environmental factors, DNA methylation measured in blood and the development of lung cancer, among participants of the CARTaGENE study, the Québec component of the Canadian Partnership for Tomorrow Project.

Land-use planning and the characteristics of the built environment are known to have an impact on the health of populations. The development and configuration of the road network and traffic flows also generate nuisances such as the emission of atmospheric pollutants with impacts on the health of populations. The objective of our project is to analyze the possible links between a number of characteristics of the built environment (e.g., transportation networks, buildings, neighborhood design and development, natural environments; food environments), and lifestyle habits (e.g. nutrition, physical activity, smoking, sleep) and the health of the Quebec population. The results will be used to specify what to change in the environment. Relatively few scientific studies in this field have used Quebec samples. The results will then validate and refine the results obtained in the United States, Australia and Europe.

Low back pain disorders are common. About 20% of North Americans are affected. Neuropathic pain is caused by an injury or a disease that affects the sensory nerves. About 5-8% of the population is affected by neuropathic pain, and conventional painkillers are usually not effective for this type of pain. This study explores the relationship between the genes of patients with low back pain and neuropathic pain and therapeutic responses. More specifically, we seek to find genetic variants related to different types of low back pain and neuropathic pain and pain management effectiveness.

One of the consequences of climate change in Quebec will be the probable increase in the frequency and duration of heat waves. Increases in projected temperatures are an important issue for the health of workers in Quebec as they are likely to increase mortality and morbidity, and the incidence of occupational injuries. The studies carried out so far do not help in identifying the workers most exposed to the effects of heat. The main objective is to develop knowledge about workers at risk and the severity of symptoms caused by heat exposure, by exploring data from the CARTaGENE cohort. This project aims to better document the profiles of workers vulnerable to heat in Quebec, to inform the public health authorities and to establish better prevention strategies.

In Canada, 1 in 2 people will be diagnosed with cancer during their lifetime, with lung and prostate cancer being the two most common cancers diagnosed. Many of these cancers may be prevented through lifestyle changes, including changes to diet and physical activity levels. However, the link between lifestyle and cancer is poorly understood. Only age and family history are well-known risk factors for prostate cancer and little is known about risk factors for lung cancer beyond smoking. This project aims to carry out a series of studies to identify the lifestyle, environmental, and genetic factors that may increase the risk that a person will be diagnosed with lung or prostate cancer. This information will inform the design of interventions to prevent these cancers in the future and improve the health of Canadians.

The increase in the prevalence of obesity around the world is mainly due to changes in our lifestyle (eating habits and physical activity), and the environment in which we live (food supply, physical and social environment). However, because of genetic factors, we are not all equally affected by these changes. Despite the fact that many genes are associated with obesity, the mechanisms by which they lead to overweight and obesity are not well known. A study conducted by our group showed that genetic susceptibility to obesity was partly mediated by dietary behaviors that favor overconsumption and weight gain. The objective of this research is to identify, within a representative cohort of the Quebec population, other nutritional, behavioral and lifestyle mediators related to genetic susceptibility to obesity.

Much of the aging process appears to be due to what we call dysregulation, the loss of balance in highly complex networks that regulate our physiology. In this project, we will extend our research using gene expression data to have a much more detailed look at how different systems in the body dysregulate during aging. These measures should provide a detailed view of who is at risk of which diseases and/or who will respond best to which medications. Overall, this project will develop ways to measure the aging process in order to improve health during aging by guiding doctors toward personalized treatments based on an individual’s profile.

Population screening has been found to decrease the mortality and morbidity of cancer. Currently, cancer screening guidelines for breast, cervical, and colorectal cancer have been implemented or are in the process of being implemented across Canada, and close to 50% of Canadian men aged 40 years and older have been screened for prostate cancer in their lifetime. Nevertheless, the degree to which both physicians and patients comply to screening guidelines, and province-specific factors that affect screening utilisation, remain unclear. This project aims to use longitudinal, nationally representative data on over 300,000 Canadians from the Canadian Partnership for Tomorrow Project (CPTP) to examine differences in uptake and correlates of adherence to breast, cervical, colorectal and prostate cancer screening across Canadian provinces.

The Canadian Partnership for Tomorrow Project (CPTP) is the product of $150+ million dollar investment to create first class infrastructure to support health research internationally. It is Canada’s largest population cohort with detailed data and biospecimens on 300,000+ adults. CPTP leaders have teamed-up with scientists from a range of disciplines to enable a deeper understanding of how air pollution and the surroundings where people live interact with genes to influence cardiometabolic health. The focus is on metabolic syndrome (MetS), a cluster of medical conditions common among aging adults: obesity, hypertension, high cholesterol, high blood sugar, and insulin resistance. Because people with MetS are more likely to develop diabetes and cardiovascular disease, MetS represents a substantial burden on healthcare systems. MetS results from the interaction of genes, lifestyle and the environment, but these mechanisms are not well understood. This project aims to quantify the effect of air pollution and built environment on MetS, and map differences in DNA that impact gene expression, and see if their effect are modified by environmental factors.

Cancer, heart disease, stroke and brain health all impact the quality of life of people living in Canada, and also increase the cost of health care. The Canadian Alliance for Healthy Hearts and Minds (CAHHM) study has enrolled Canadian Partnership for Tomorrow Project (CPTP) cohort participants (along with other participants in CAHHM recruited from other cohorts, such as CARTaGENE) and will integrate the CPTP core questionnaire data of these participants, to better understand the early causes and risk factors of vascular diseases. The research team is also interested to determine how the places in which we live and work influence our lifestyles such as physical activity, food intake, and stress. Specifically, the CPTP core questionnaire data will inform the sociodemographic, medical history, lifestyle factors, family history related to cancer and chronic diseases risk. By better understanding the causes of poor health and diseases, the research team will be able to identify key risk factors and learn how to identify poor health early in order to optimize health services access and treatment for at risk individuals.

Solar ultraviolet radiation (UVR) is a global exposure that can be both beneficial and harmful to cancer initiation, depending on the degree and type of exposure. The relationship between exposure to UVR, melanoma and non-melanoma skin cancers is already understood. Melanoma is typically associated with intense irregular periods of sun exposure, while non-melanoma skin cancers tend to develop from long-lasting sun exposure. A certain level of sun exposure is potentially protective for some other cancer sites through the production of vitamin D. However, a strong body of evidence supports an association of non-melanoma skin cancers with elevated risk for developing other cancers, providing some evidence of a potential relationship between chronic sun exposure and risk for other cancers sites. The assessment of risk associated with ambient UVR, time spent in the sun and sun behavior habits (sunburn and sunbathing) with non-skin related site-specific cancer development remains limited in large longitudinal studies. Results from the study could provide clarity on the beneficial and detrimental types of UVR exposure for site-specific cancer development.

Niemann-Pick type C (NP-C) disease is a rare neurodegenerative disease associated with mutations in the NPC1 and NPC2 genes. Only a few patients are diagnosed in Quebec, but international stats suggest that it is possibly underdiagnosed. NP-C is a neurodegenerative disease whose progression can be slowed down, therefore it is very important to identify as many cases as possible. In this project, we propose to use available data from CARTaGENE to determine the prevalence of mutations in the NPC1 and NPC2 genes in the Quebec population. Moreover, our analysis will help define the mutational traits of NPC1 and NPC2 in the Quebec population. Ultimately, this study might offer larger diagnostic capacity and greater accessibility to treatments for these patients.

The prevalence of cardiometabolic diseases, also known as cardiometabolic diseases, such as cardiovascular disease, type 2 diabetes, and obesity is rising in Canada. Most of these diseases are caused by a combination of environmental factors, lifestyle as well as inherited (genetic) risk factors. Despite considerable progress in our understanding of the factors that contribute to the development of cardiometabolic diseases, few therapeutic approaches have been proven effective for the prevention of these diseases. The platform CARTaGENE provides a unique opportunity to identify new genes that may potentially represent drug targets for cardiometabolic diseases and to determine whether these genes may represent safe and effective targets for the prevention and management of cardiometabolic diseases.

The field of pharmacogenomics (drug responses based on our genes) has become one of today's most promising aspects of personalized genomics. Progress in this field is allowing a better understanding of the biology involved in drug sensitivity, efficacy, and toxicity. Preliminary evidence suggests that the genes implicated, known as pharmacogenes, can also lead to a different risk of disease in people who have them. We hypothesized that these extended traits and genes have been shaped by natural selection, in response to diet and environmental exposure throughout human history. To test this hypothesis, we propose to use the CARTaGENE data to identify systematically these signatures in known pharmacogenes. Identification of genetic mutations that have systemic disease risk as well as altered drug response will provide insights to help to optimize genetic testing strategies as well as drug therapy, leading to better prevention of adverse effects of treatment in personalized medicine.

Both genetics and the environment play an important role in health and disease. However, studies that have investigated the relationship between genes and diet-related chronic diseases often report low effects of genetics. It is therefore likely that the interaction between genetics and environmental factors has the largest impact. This research will evaluate the interaction between environmental food cues and genes involved in human behavior, taste perception, and obesity risk on nutrition and health outcomes using one of the largest population cohorts in Canada. Statistical analyses will be conducted to determine whether gene variants interact with environmental food cues to influence dietary patterns and indicators of cardiometabolic health (e.g. body mass index, waist circumference, LDL cholesterol). Findings from this investigation will assist in better understanding genetic and environmental risk factors for chronic diseases and will lead to the development of more targeted prevention strategies.

Women who inherit a genetic mutation resulting in loss of function of BRCA genes have a significantly higher risk of developing ovarian cancer. Although carrier individuals have been found in the majority (50-80%) of families with a history of breast and / or ovarian cancer; hereditary cancer of the ovary is not all due to these genes. It has become clear that the missing ovarian cancer risk genes are most likely due to rarer mutations. Moreover, identifying new risk genes is challenged by the relative rarity of familial ovarian cancer cases not due to BRCA genes. Thanks to the unique genetic demography of Quebec's French-Canadian population, disease-associated mutations are more likely to occur in people with cancer than in healthy people. We found a FANCI gene mutation that would affect its function. To characterize this mutation, we will compare the frequency of mutation carrier women with ovarian cancer from ovarian cancer families or non-familial cases to healthy women from the French Canadian population, using genetic data from CARTaGENE.

Worldwide, colorectal cancer is the third most common cancer and men are more likely to develop colorectal cancer than women. Different environmental, lifestyle, and biological factors may explain this difference. Estrogen, a hormone that promotes the development and maintenance of female characteristics, has a role in the prevention of colorectal cancer in women. Less is known about the role of hormones in the development of colorectal cancer in men, but the proper functioning of sex hormones also appears to prevent colorectal cancer. Endocrine disruptors are chemicals that interferes with the proper functioning of sex hormones. Although we are exposed to these chemicals in the environment and in our diet, workers in certain sectors are highly exposed to endocrine disruptors. In this research, we will examine whether exposure to endocrine disruptors in the workplace increases the risk of colorectal cancer.

Our research will be based on participants of the Canadian Parternship for Tomorrow Project. This study will include all men and women who were newly diagnosed with colorectal cancer since 2009 and who have shared information on their health, lifestyle, environment, and behaviours. An interview will determine whether exposure to endocrine disruptors at the longest held job was probable or not. We will compare the number of colorectal cancer cases among participants who were probably exposed to endocrine disruptors to those who were never exposed. This study offers a valuable opportunity to examine whether endocrine disruptors play an important role in colorectal cancer risk.

For several years, blood banks around the world have turned to genetic analyzes to predict the presence or absence of blood group antigens on red blood cells to avoid incompatibilities during blood transfusion and the risk of fatal post-transfusion reactions. A genetic variation, called D, has been identified as part of these activities and appears to be predominant in the population of Quebec. We do not yet know the impact of this variant on the care to be given to patients, especially for pregnant women, about the possibility of receiving immunoglobulins during pregnancy. This project aims to identify the prevalence of this variant in the Quebec population.

Osteoarthritis (OA) is the most common joint disease, with complex progression and numerous molecular processes involved. OA represents the major cause of chronic disability in aging adults and a growing economic problem for our society. The search for the mechanism of genetic expression in OA cartilage and bone has led Dr. Moreau and his team to discover a new and unrecognized role for nuclear prohibitins. They hypothesize that increased activity of these prohibitins promotes OA beginning and progression through the regulation of key effectors involved in cartilage. The purpose of this study is to better understand OA disease, develop specific predictive OA biomarkers and identify new therapeutic targets.

Despite well-established associations between modifiable lifestyle and environmental risk factors and cancer risk, reductions in these risk exposures have not produced declines in cancer incidence in Canada. This lack of change could be due to inadequate awareness among Canadians about the modifiable causes of cancer, and population-based cancer prevention strategies based on outdated information. To improve on this, we are conducting a study that will estimate the number of cancer cases, now and in the future, that could potentially be prevented through changes in modifiable lifestyle and environmental risk factors associated with cancer. These risk factors include tobacco smoking, dietary intake, physical activity level, body weight, environmental factors, infectious diseases and hormonal therapies. This study will produce the most comprehensive dataset of its kind ever in Canada based on the most up-to-date epidemiologic evidence of cancer risk and contemporary exposure prevalence data. This information will be invaluable for a broad range of knowledge users including policy makers, to target the exposures and cancer prevention interventions with the greatest potential for population-level impact.

The depression rate is nearly twice as high in people with type 2 diabetes compared to those without diabetes. The mechanisms behind the association between depression and diabetes are poorly understood. New evidence suggests that inflammation may play an important role in the progression and reappearance of depression in people with type 2 diabetes. Dr. Schmitz’s study seeks to examine the association between inflammation and depression in individuals with type 2 diabetes. Results indicating that inflammation is a risk factor for depression in people with type 2 diabetes would suggest that depression treatment strategies targeting inflammation should be established and tested. These results might provide important information to both clinicians and the public.

This research project aims to clarify the genetic mechanisms associated with myalgic encephalomyelitis, most commonly known as the fatigue chronic syndrome. Chronic fatigue syndrome is a complex physical disease characterized by debilitating fatigue, post-exercise discomfort, pain, mental problems, sleep disorders and a host of other symptoms affecting the immune, neurological and autonomic nervous systems.

Dr. Moreau, and his team, work on identifying genes and genetic mutations specifically associated with the chronic fatigue syndrome, in order to better understand its genetic component, its hereditary transmission and possible gene-environment interactions.

Copy Number Variants (CNVs) are defined as a deletion or a duplication of a genetic fragment. CNVs have emerged as important initiators to neuropsychiatric disorders. CNVs that are harmful for neurodevelopment are individually rare but recent studies demonstrate that collectively, their prevalence (1 to 3% considering their size) and their impact on cognition is high in the general population. Notably the largest CNVs increase the risk of intellectual disabilities and decrease the level of education. CNVs previously associated with autism and schizophrenia have further been studied, and it is estimated that they reduce general cognition. The goal of this study is to investigate, the effect of rare harmful CNVs on cognitive and behavioral traits as well as the impact and burden on the health system in the general population.

Being physically active have been shown to reduce the risk of some cancers. There are different types of physical activity, including activity at work and recreational activities. Participation in recreational activities has shown to reduce lung cancer risk. However, the role of physical activity at work in affecting the development of lung cancer is not well established. In fact, some studies have found that people who have physically demanding jobs also have a higher risk of lung cancer. As people spend many hours at work and some jobs are very physically demanding, new studies are needed to fully understand the role of physical activity at work on lung cancer development. This research will examine how lung cancer risk is associated with physical activity level at work. The collected information, including details such as the activity levels in the longest-held job for all participants, were used for comparison between those who were diagnosed with lung cancer and those who remained cancer-free. This study offers a valuable opportunity to examine whether physical activity at work plays an important role in lung cancer development.

Vitamin D supplements are transformed to 25 hydroxyvitamin D (25OHD) levels in our blood. This study aims to compare the response to vitamin D supplements of individuals carrying a specific vitamin D related genetic mutation (carriers) compared to individuals without the mutation (non-carriers). This genetic mutation affects a key enzyme in vitamin D metabolism, named CYP2R1, leading to reduced conversion of vitamin D to 25OHD. The study will have direct clinical relevance, since these individuals have low 25OHD levels and efforts to increase their 25OHD level are likely to be delayed by their genetic mutation in CYP2R1. After a series of tests and supplement intake, they will perform blood draws for measurement of 25OHD levels before and after treatment in both groups and compare the change in 25OHD between carriers and non-carriers. The main reason for using CARTaGENE participants for this study is the availability of genotyped data in a large sample of individuals, enabling enough number of cases and controls to test our study hypothesis.

The research program PERSPECTIVE (Personalised Risk Stratification for Prevention and Early Detection of Breast Cancer) is a large research program concerning breast cancer. Dr. Simard is using CARTaGENE’s samples and data to identify the effects of common genetic variants (SNPs) on the risk of developing breast cancer. Therefore, he wishes to clarify the genetic and non-genetic risks associated with this disease.

Chronic kidney failure is a major health problem. Fractures and vascular calcification are complications of chronic renal failure. This disease includes changes in mineral metabolism and clinical consequences such as fractures and cardiovascular events. It has recently been shown that bone cells secrete important regulators of osteogenesis. These mediators of bone formation are associated with vascular and bone abnormalities of chronic renal failure in animal models. However, their association with clinical events in chronic renal failure is less well known. The main goal of Dr. Mac-Way is to determine if these markers are predictive of the occurrence of fractures and cardiovascular events in patients with moderate chronic renal failure. To do this, they will measure the levels of markers specific to bone cells, in addition to markers of bone metabolism and additional biochemical markers. This project will highlight the role of bone tissue’s markers in the development of vascular and bone abnormalities from chronic renal failure. In the long term, their results will make it possible to better target patients with chronic renal failure at risk for vascular and bone complications and to develop targeted treatments.

Aortic stenosis (AS) occurs when the heart's aortic valve narrows. This prevents the valve from opening fully which reduces the blood flow from your heart into the main artery to your body and onward to the rest of your body. Despite the large burden of disease due to AS, no large scale genetic studies of clinical AS have been performed. Knowledge of the genetic determinants of AS could help explain the biological mechanisms leading to clinical valvular heart disease. Dr. Thanassoulis and his team aim to validate recent findings from a study of aortic valve calcification in a case-control study of clinical AS, and to identify novel genetic variants associated with AS. Their project will allow for the discovery of new common genetic variants associated with AS, which will lead to an improved understanding of the underlying biology of AS and may provide future insights into the prevention of this disease.

An individual with hereditary cancer predisposition syndromes may develop cancer at an early age, or multiple cancers, and may even have a family history of cancer. The French Canadian population of Quebec is a unique population with a specific genetic background, with different mutations in multiple genes and population-specific changes. The French Canadian population is largely understudied even with the publicly available genomic databases. This poses challenges in analyzing the potential disease-causing of identified genetic mutations.

Dr. Foulkes’ team frequently recruits individuals and families from Hereditary Cancer Clinics in Montreal with histories of cancer that might have hereditary cancer predisposition syndromes but with no genetic cause. His goal is to build a control group with no prior personal nor familial cancer history in order to compare and identify genetic mutations in other French Canadian cases.

This project aim to identify novel genes that could help in cancer diagnosis, and to provide information about the relation between the type of cancer and gene mutations in hereditary cancer predisposition syndromes in the French Canadian population.

Ce projet vise à identifier de nouveaux gènes pouvant aider au diagnostic du cancer, et à fournir de l'information sur la relation entre le type de cancer et les mutations génétiques associées au syndrome héréditaire de prédisposition au cancer dans la population canadienne-française.

Thanks to technological advancements, it is now possible to look for DNA sites that vary between participants in hundreds of thousands of locations, called SNPs for "single nucleotide polymorphisms". Dr. Lettre and his team will use statistical approaches to identify associations between genes and diseases in the CARTaGENE cohort. Phenotypes of interest will focus on cardiometabolic traits (eg, blood lipids, myocardial infarction, hypertension, diabetes), anthropometric traits (eg, height, body mass index, obesity), and blood lines (eg red blood cells, white blood cells, platelets). These results will make it possible to trace a genetic profile of these traits in the population of Québec. In addition, they will optimize genetic prediction and evaluate the potential of certain genes as therapeutic tools.

Rapid eye movement sleep behavior disorder (RBD) is a sleep disorder characterized by the loss of inhibition of voluntary muscles during the sleep phase with rapid eye movement sleep. This means that individuals with RBD enact their dreams. Interestingly, it was proven that 10-12 years in average after diagnosis of RBD, these patients might develop one of three diseases such as Parkinson’s disease, dementia with Lewy-bodies or multiple system atrophy. Dr. Gan-Or and his team assembled the world’s largest cohort of individuals with RBD and is performing a genome-wide association study. About half of the cohort’s RBD patients are French-Canadian or French, others have Parkinson’s disease and the rest are mainly controls. Their aim is to identify genetics factors associated with RBD and Parkinson’s disease while evaluating the role of genetics in the rate and type of progression of the previously mentioned diseases.

Sleep disorders are generally common. Understanding the genetics behind normal versus disrupted sleep is essential in identifying new treatments for sleep disorders. Previous studies have shown that sleep disorders are heritable. Even with being heritable, few genetic causes have been linked to them. Dr. Warby aims to identify new genetics causes associated specifically with insomnia and sleep duration.

This project aims to explore different approaches of data harmonization by examining the determinants of age at menopause among participants of large population-based studies. Age at menopause is related to women’s health. In addition, it is considered as a marker of human health as its late occurrence may reduce risks of cardiovascular diseases and its early occurrence may reduce risk of breast, cervical and endometrial cancers. Through this study, the research team will use and compare different methods of data harmonization to assess the lifestyle, sociodemographic, environmental, and reproductive health-related factors related to age at menopause in Canada and these results will be compared to European studies. Age at menopause and all confounding factors data will be obtained from baseline assessments of LifeLines, the Canadian Partnership for Tomorrow’s Project and UK-Biobank studies.

Eczema, also known as atopic dermatitis, is a common skin condition that has been associated with risk factors for heart disease and stroke. Very few studies have actually looked at whether eczema predisposes people to develop heart attacks or strokes. The research team plan to use data from the Canadian Partnership for Tomorrow Project to investigate whether having eczema makes people more likely to develop high blood pressure, diabetes, heart attacks or strokes. It is expected to find that people with eczema do develop high blood pressure, diabetes, heart attacks and strokes more than people without eczema. If our findings are consistent with our expectations, that would lead to further research into why people with eczema are at higher risks and to efforts to decrease the risk of those conditions in patients with eczema.

Although all-purpose genetic studies provide a promising approach to study the genetics of complex diseases, it is clear that these studies have not yet explained most of the underlying genetic risks for schizophrenia and bipolar disorder. The goal of the project is to identify the genes responsible for these risks from large Eastern Québec participants that are followed-up. This project is also complementary to international all-purpose genetic studies completed on a large number of unrelated subjects aimed at identifying small effect genes since the nature of the results and of the participants’ number of this project leads to less common related genes with relatively large effects.

Mitochondria, found in our cells, are involved in a wide range of fundamental biological processes. The genetics and function of mitochondria are involved in different diseases. Despite this, very little is known about the genetic results of mitochondria varying across individuals and whether these events influence diseases. Here we aim to uncover differences in the genetics, gene expression and processing of the mitochondria and identify associated genetic and molecular signals through tests. This work will provide major new understandings into the underlying mechanisms influencing mitochondria processes across individuals.

Mental health problems and poor sleep are associated with increased risk of heart disease. However, mental health and poor sleep often occur together. The objective of this study is to determine if poor sleep and poor mental health are independent risk factors for incident heart disease.

The incidence of heart diseases will compare six groups: a) no depression and normal sleep duration; b) no depression and short sleep duration; c) no depression and long sleep duration; d) depression and normal sleep duration; e) depression and short sleep duration; and f) depression and long sleep duration. The above analyses will be repeated with anxiety. CARTaGENE data are used because the large sample is expected to provide sufficient power for the mentioned analyses. Moreover, detailed assessments of risk variables were collected and this data can be linked to measures of any variable of interest in heart diseases.

Restless Legs Syndrome is a common sensor and physical disorder characterized by an abnormal sensation and urge to move the legs, typically before sleeping. About 5-15% of the North-American population suffer from restless legs syndrome, and its cause is still not clear, although it is clear that genetics is an important component of its progression. There are six known genes that are associated with the risk for restless legs syndrome, and the possibility of inheriting it is up to 70%. Dr. Rouleau and his team’s objective is to identify genetic risk factors that are associated with either increased or decreased risk for restless legs syndrome. For that purpose, they are taking part in an international genetic study. CARTaGENE will allow them to achieve their goal and further expand the knowledge on the genetic cause of restless legs syndrome.

Central blood pressure and artery stiffness are independent indicators of cardiovascular attacks in high-risk patients with higher blood dynamics parameters. However, uncertainties remain as to the importance of (i) central blood pressure in low-risk individuals and of (ii) artery stiffness as data is lacking or inconclusive. For example, a recent analysis has shown that the increase index was independently associated with increased cardiovascular disease and death. However, this analysis was comprised of small studies with relatively short duration (<5 years) with a high proportion of patients with different diseases. This confusion, in results from different studies, prevents the use of central blood dynamic parameters in cardiovascular risk assessment. We hypothesise that central blood dynamic parameters are associated with adverse cardiovascular events independently of peripheral blood pressure in the general population. Our goal is thus to evaluate and compare the impact of elevations of central and peripheral blood dynamic parameters on the occurrence of cardiovascular events. CARTaGENE’s populational cohort and medico-administrative databases will allow us to achieve this objective. We anticipate this study will be the first to show the utility of using central blood dynamic parameters to enhance cardiovascular risk prediction in the general population.

The “Canadian Alliance for Healthy Hearts and Minds”, herein referred to as the Alliance, aims to improve our understanding of the impact of individual, socio-economic and other environmental factors leading to cardiac and vascular disease.

Participants were assessed using questionnaires, physical measurements, MRI scan and blood samples. In addition, the study examined the role of background and individual risk factors such as the built, physical activity, nutrition, and tobacco environments, as well as social capital and social ties on the development of cardiovascular disease. Access to CARTaGENE data was requested to create health and health services profiles for communities in the province of Quebec. Data from the baseline CARTaGENE questionnaire were linked with Quebec RAMQ and MED-ECHO administrative health databases in order to provide a rich data source for studying the relationship between risk factors (screening, management), health behaviors, health services access and utilization, and outcomes. The baseline demographic data, along with the indicator data, were used to create the community profiles. Similar profiles were created for other communities across Canada using comparable data to study the causes of cardiovascular dysfunction and geographical variations in cardiovascular disease incidence. 

Health Canada asked to fill important knowledge gaps regarding the safety and effectiveness of various drugs. Dr. Bernatsky and her team will use a combined approach, with both clinical cohort data and administrative data, to address the question. The first aim of this project is to evaluate whether mental affecting medication use (selective inhibitors of serotonin or norepinephrine reuptake) is associated with fracture risk. The second objective of this project is to study the comparative effectiveness of antihypertensive treatments among older adults without diabetes, focusing on thiazides monotherapy compared with other monotherapy. Finally, this project will evaluate short-term safety and comparative effectiveness of an insulin analog compared to a natural derivative by studying the risk of hypoglycemia.

Metabolic Syndrome (MetS) is a group of five component risk factors (high blood pressure, high blood sugar levels, high triglycerides, low HDL cholesterol, and large waistline) associated with an increased risk of heart disease, stroke, and diabetes. Research into metabolically healthy obesity (obese individuals without obese-related metabolic abnormalities) has shown that obese individuals may not always show adverse metabolic profiles characterized by MetS. Diet and nutrition are lifestyle factors whose effect on MetS and metabolically healthy obesity are not well understood. Some research has shown associations between specific food types and dietary patterns with conditions. However, the relationship between a vegetarian diet and the MetS risk factor components and inflammation is less known. This project aims to explore associations between adherence to a vegetarian diet and commonness of MetS, microinflammation and metabolically healthy obesity.

This study will make use of data collected by multiple European and Canadian studies to examine these associations, benefiting from a very large statistical power and making it easier to detect effects both within and between participating cohorts.

Chronic Obstructive Pulmonary Disease (COPD) is a progressive disease that is characterized by loss of lung function, leading to breathlessness, poor quality of life, loss in productivity and high death rate. COPD patients frequently experience acute exacerbations (AECOPD), i.e “lung attacks”, during which breathlessness, coughing, and phlegm production dramatically increase, leading to emergency admissions and hospitalizations. AECOPD can be effectively managed if they are identified and treated early, but symptoms often overlap with those of other common conditions such as heart failure, pneumonia and influenza. Because there are no tests that can separate AECOPD from these conditions;  doctors  struggle to  accurately diagnose  AECOPD at  an  early stage when  drug treatments are  most effective. This can lead to a delayed or even incorrect diagnosis and inappropriate treatment. 

The goal of this project is to improve COPD patient care by developing new blood tests that will help identify patients at high risk of AECOPD and those who are in the early stages of an AECOPD. Doctors will be able to use these tests to prevent AECOPD or treat them at earlier stages. 

Dr. MacNamara’s team has already identified promising protein, gene, and DNA blood markers that can predict and diagnose AECOPD from a simple blood draw. Samples from CARTaGENE’s participant would be useful for validating these biomarkers.

Adolescent Idiopathic Scoliosis (AIS) is a common complex genetic disease. Most severe cases of AIS are females (90%) and the genetic causes are still unclear. Evidences of genetic influences come from epidemiologic studies of family history and family groups, and twin studies. Dr. Moreau and his team investigated the contribution of common mutations to AIS through a wide genome study. They expected to detect strong associations in the French-Canadian cohort because of reduced population diversity and the higher than average disease commonness.

Research has consistently demonstrated that low density lipid-cholesterol (LDL-C) level is a predictor of cardiovascular disease, death, and medical costs. This problem is emphasized for patients with high risk of having a cardiovascular event. The Canadian Dyslipidemia Guidelines highlights these patients and mentions they should be managed to lower LDL-C and reduce their cardiovascular risk. Lowering LDL-C through lifestyle changes and medication can lower the risk of a recurrent cardiovascular event.   

The primary objective of this project is to evaluate the occurrence of high cardiovascular risk patient in the CARTaGENE cohort representative of the population of Quebec. The baseline characteristics, the medication profile and the recurrence of cardiovascular events will also be defined. In addition to these factors, the secondary objective of this project is to evaluate the familial history, the economic impact and the health care resource utilization of high cardiovascular risk subpopulation. This project will help have a better understanding of the burden caused by the high cardiovascular risk population.

Two major regulatory hormonal networks in the central nervous system are involved in the pathology of bipolar disorder. Many external factors such as sleep, stress, daily rhythm affect their activity. Dr. Vuckovic and this team hypothesize that it is necessary to monitor simultaneously the status of these two networks in order to obtain the most clinically useful data to support patient diagnosis and response to treatment. They will achieve this by measuring concentrations of important metabolites implicated in bipolar disorders and comparing their levels to those found in control population and populations suffering from related mood disorders (major depression and schizophrenia).

Type 2 diabetes is one of the most common chronic diseases that continues to increase in numbers and significance. Metabolic abnormalities, such as central obesity, elevated blood pressure, uncontrolled sugar levels, systemic inflammation, adverse high-density lipoprotein cholesterol (HDL) and adverse triglycerides are important risk factors for type 2 diabetes. Recent research suggests that depression with metabolic abnormalities, labeled as metabolic depression, could represent a distinct psycho-metabolic syndrome. The co-occurrence of these two conditions might increase the risk of developing type 2 diabetes. This project will evaluate the interaction between depression and metabolic abnormalities on type 2 diabetes incidence in the CARTaGENE cohort. Understanding the associations and interactions between depression, metabolic abnormalities and behavioral factors might lead to better identification of individuals at high risk of developing type 2 diabetes. These results could have a massive impact on the development of effective diabetes prevention and intervention strategies.

Dr. Goodyer studies the role of the human growth hormone receptor during development. More specifically, her team already investigated the characteristics within the DNA regions (single nucleotide and polymorphisms) that regulate the gene expression of growth hormone receptor in idiopathic short stature children and control height adults. By using genomic DNA from CARTaGENE’s cohort, this project would validate the differences obtained in a much larger cohort of idiopathic short stature adults.

The Czech post-MONICA study is a population survey examining the occurrence and treatment of cardiovascular risk factors in the general population of the Czech Republic. The aim of this study directed by Dr. Hamet is to replicate the genome-wide study results from the Czech post-MONICA discovery cohort in CARTaGENE’s cohort and to perform a genome-wide association study of the principal components of the metabolic syndrome score. From the czech individuals, we selected those along with the metabolic syndrome and increased albuminuria. We matched them by age and gender to the two sets of control group: 1. individuals not presenting with metabolic syndrome nor with increased albuminuria, 2. individuals presenting with identical metabolic syndrome criterion but without increased albuminuria. Urinary albumin, creatinine and albumin/creatinine ratio in the French Canadians from CARTaGENE will be analyzed and combined analysis on pooled data will be performed.

Chronic rhinosinusitis (CRS) is an inflammatory disease of the upper respiratory tract. Despite its importance, CSR is associated with inflammation of the mucosa interacting with the normal bacterial group of our body. However, the factors conferring a susceptibility to the development of the disease remain unknown.

Dr. Desrosiers and his team believe that genetic studies will identify variations and mechanisms involved in the development of CSR. This team has already identified candidate genes and signaling pathways associated with CSR that have a functional impact on biomarkers or demographics. The use of the genotyped cohort of CARTaGENE as a control population will confirm the observations already made and will identify new mechanisms involved in the CSR that can be validated in various transactional models.

The impact of environmental and genetic factors on metabolism is largely unknown. However, they are directly related to the biology of several chronic diseases in aging populations, such as obesity and cardiovascular disease. The project proposed by Dr. Awadalla aims to improve the understanding of the mechanisms through which the environment interacts with genes to define the progression of cardiovascular diseases. This will enable the identification of genetic biomarkers of cardiovascular diseases in the Quebec population as well as their environmental modulators.

Teen scoliosis is a three-dimensional deformity of the spine affecting 1 to 3% of the pediatric population aged 10 to 18 years. Teen scoliosis has a spectrum of very broad clinical manifestations, ranging from non-progressive mild forms to severe forms most often requiring surgery. Prognostic tools must be developed to anticipate the onset of progressive scoliosis in adolescents, and to propose a preventive therapeutic approach adapted to patients. In this perspective, a biochemical approach was developed in Dr. Moreau's laboratory. For the moment, it is possible to classify patients into three distinct groups for which the pathology is inherited, depending on the intensity of the observed functional defect. This approach being cumbersome and expensive, it appears necessary to develop a genetic test. The objective of this project is to validate the genetic markers defining the specific signature of each of the three groups identified by Dr. Moreau and his team, in order to develop an affordable genetic test.

The project aims to explore the genetic backbone for congenital heart disease, the second most common cause of infant death in Quebec. The genetic factors underlying most complex heart malformations remain largely unknown. Recruitment of families of sufficient size has been a limiting step in the genetic exploration of this complex trait. Recently, Dr. Andelfinger and hit team have identified a large family in the Lac St-Jean area in which multiple males are affected with congenital heart disease. The subsequent analysis resulted in the identification of a genomic region on the X-chromosome. They also have identified mutations in the collagen genes, which play an important role in heart valve development and maintenance.

The availability of the control CARTaGENE’s cohort contributed in identifying rare genetic variants, which are specific to the French Canadian population, but not to congenital heart disease. The nature of the disease suggests that genetic variants increasing the risk of congenital heart disease have been selected over evolutionary time. The unique founder population of Quebec might provide insights into the role of identical genes and help to pinpoint rare and common gene groups carrying disease mutations. In turn, data from this project will help to inform further genetic studies, in particular those targeting cardiovascular phenotypes. 

Chronic kidney disease is a widespread public health problem. Defined by the presence of structural or functional damage, this condition decreases renal function for more than three months. Chronic kidney disease is common in the Quebec population, but are often unaware of their condition.

The objective of this project is to assess the prevalence of kidney disease in the CARTaGENE cohort. Dr. Madore's research has shown that only 8% of CARTaGENE participants with chronic renal failure are aware of their condition. This study shows the consequences of underdiagnosis of chronic kidney disease in Quebec, particularly with regard to the identification of risk factors, treatment management and patient education.

Previous studies suggest that depression may be associated with risk of osteoporosis and fractures. Dr. Bernatsky and her team aim to evaluate whether the use of medication that affects the mental state is associated with the risk of bone fracture. They will use CARTaGENE’s data to ascertain a group of individuals exposed to psychotropic medications, as well as a control group composed of unexposed subjects. The outcomes will be established through administrative data linkage, such as physician billing and hospitalization records.

Zellweger syndrome is a rare genetic disease with latent transmission. It is usually manifested in the neonatal period by severe neurological disorders and dysfunction of several organs. Death usually occurs within the first year of life. Despite global genetic diversity, Dr. Bouchard's team has identified a mutation in a gene for all patients diagnosed in the last 20 years in Saguenay-Lac-St-Jean. In addition, three other mutations have also been identified in Quebec.

This study will increase our knowledge of the genetics of Zellweger syndrome in Quebec and develop a molecular test to increase reproduction options of affected families. This project will also establish the proportion of people carrying these mutations in the different regions of Quebec. Finally, this study will generate the necessary evidence for the evaluation process of a voluntary population screening of carriers at Saguenay-Lac-St-Jean.

Based on the genealogical reconstructions, Dr. Tremblay and his team aim to draw a demographic and genetic portrait of the CARTaGENE participants recruited during phase A. The analysis of these genealogies will make it possible to characterize and compare the samples from the four surveyed regions (Montreal, Quebec City, Sherbrooke and Saguenay). Several parameters will be investigated in order to provide the most complete and useful information possible on the demo-genetic characteristics of the populations concerned. In addition, the genealogies will be paired with other survey data pertaining to the same individuals, which is a particularly interesting and innovative aspect. Indeed, it will be the first time that such data will be available for such a large sample of the Quebec population. The expected results will better characterize the origin of individuals in each region as well as their migratory route, which will then help better describe the recent evolution of regional genetic pools.

Dr. Bernatsky's research project focuses on the link between air pollution (fine particles and sulfur dioxide) and the autoimmune response that could lead to rheumatoid arthritis. The researchers found a statistical association between the levels of air pollution exposure and the levels of antibodies measured in the samples from the participants of CARTaGENE. These results reinforce initiatives to improve air quality in reducing the burden of chronic environmental diseases.

New findings suggest that spatially expanding populations will accumulate harmful mutations at a higher rate than stationary populations. Natural selection would be ineffective in the small populations at the front of the expansion. This accumulation of mutations is called the expansion load. Certain regions of Quebec such as Saguenay-Lac-St-Jean have experienced spatial expansions. Recent genealogical analyzes revealed, among other things, that the majority of Saguenay-Lac-St-Jean ancestors had lived on the expansions fronts and that they had left a greater genetic contribution that could be partially due to the expansion load. It seems that the analysis of the genomic diversity of individuals from Saguenay-Lac-St-Jean, or other regions with recent expansions, would offer a unique opportunity to test our theoretical predictions.

Dr. Excoffier's team aims to show that individuals whose ancestors evolved on a colonization front accumulated a greater number of harmful mutations than others. These results would otherwise explain the high frequency of some recessive diseases in newly populated areas (as in Saguenay-Lac-St-Jean or Finland). 

Human Herpesvirus 6 has a remarkable peculiarity that distinguishes it from other human herpes viruses. Indeed, 1% of the world's population has a chromosomal integration of the human herpes virus 6 in each cell of their body. This genetic alteration is transmitted from generation to generation as a gene. The mechanisms and consequences of such integration remain unknown, but those with the integration of this virus are twice as represented in diseased cohorts. The objective of this project is to determine the contribution of the chromosomal integration of the Human Herpesvirus 6 and its integration site, in order to target cohorts prone to these diseases.

Chronic renal failure is a widespread public health problem. Defined by the presence of structural or functional damage, this condition causes a decrease in renal function for more than three months. Chronic kidney disease is common in the Quebec population, but there is still little data in middle-aged people.

The objective of this project is to evaluate the prevalence of chronic renal failure in the CARTaGENE cohort. Dr. Madore and his team would like to have a better idea of the importance of the disease in a population of middle-aged individuals particularly at risk of developing the disease and thus compare the results with the prevalence of the disease elsewhere in the world.

The analysis of metabolites in body fluids provides a better understanding of the changes generated by the disease or by exposures to toxic substances. The main objective of Dr. Ayotte's project is to identify the profile of the metabolites present in the urine of indigenous populations following the consumption of methylmercury in fish. This project will help improve knowledge on the impacts of chronic exposure to methylmercury, and to validate the scientific approach used in a large population cohort such as CARTaGENE.