An investigation of gene-environment interaction on eating behaviour and adiposity in a cohort of Quebec adults Researcher: Dr. Daiva Nielsen

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.

Genetic analyses of proposed new ovarian cancer predisposing gene Researcher: Dr. Patricia Tonin

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.

Occupational exposure to endocrine disrupting chemicals and colorectal cancer risk Researcher: Dr. Vikki Ho

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.

Prevalence study of blood group D antigen Researcher: Dr. Josée Laganière

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.

Role of prohibitins in osteoarthritis pathogenesis Researcher: Dr. Alain Moreau

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.


Inflammation and the risk of depression in people with type 2 diabetes Researcher: Dr. Norbert Schmitz

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.

Discovery of genome variations in chronic fatigue syndrome Researcher: Dr. Alain Moreau

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.

Impact of structural genomic variants on cognition in the general population Researcher: Dr. Sebastien Jacquemont

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.

Occupational physical activity and lung cancer Researcher: Dr. Vikki Ho

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.

Impact of genetic variations on the response to vitamin D therapy Researcher: Dr. Brent Richards

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.

Study of genetic variants associated with an increased risk of breast cancer Researcher: Dr. Jacques Simard

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.

Association between certain markers of bone tissue and the frequency of fractures and cardiovascular events in a context of chronic renal failure Researcher: Dr. Fabrice Mac-Way

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.

Genetic study of aortic stenosis Researcher: Dr. George Thanassoulis

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.

Evaluation of genetic variations associated with the hereditary syndrome of cancer predisposition in the French-Canadian population Researcher: Dr. William Foulkes

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.

Genetic analysis of cardiometabolic diseases in the CARTaGENE cohort Researcher: Dr. Guillaume Lettre

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.

REM sleep behavior disorder and progression of Parkinson’s disease Researcher: Dr. Ziv Gan-Or

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.

Genetic basis of sleep disorders Researcher: Dr. Simon Warby

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.


Genomic follow-up of schizophrenia and bipolar disorder in families of Eastern Quebec Researcher: Dr. Michel Maziade

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.

Genetic analysis of the mitochondrial transcriptome Researcher: Dr. Alan Hodgkinson

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.

Poor sleep and mental health: independent or overlapping risk factors for heart diseases Researcher: Dr. Norbert Schmitz

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.

Deciphering the genetic background of restless legs syndrome Researcher: Dr. Guy Rouleau

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.

Study of the predictor role of central aortic pressure in the occurence of cardiovascular events Researcher: Dr. Rémi Goupil

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.


Canadian Alliance for Healthy Hearts and Minds: Development of community health and health services profiles Researcher: Dr. Jack Tu

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. 

Comparative effectiveness of medications used in diabetes and hypertension Researcher: Dr. Sasha Bernatsky

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.

Associations between vegetarian diet, the metabolic syndrome, obesity and inflammation Researcher: Dr. Isabel Fortier

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.

Predictive Blood Biomarker Study of Chronic Obstructive Pulmonary Disease Researcher: Dr. Elisabeth MacNamara

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.

Identification of genes involved in adolescent idiopathic Researcher: Dr. Alain Moreau

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.

Evaluation of coronary vascular disease among high cardiovascular risk patients in the cohort CARTaGENE Researcher: Dr. Thao Huynh

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.

Simultaneous systematic monitoring of hormonal pathways in bipolar disorder Researcher: Dr. Dajana Vuckovic

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).


Identifying behavioral, metabolic, or mental factors that may promote type 2 diabetes Researcher: Dr. Norbert Schmitz

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.

Regulating the expression of growth hormone receptors during development Researcher: Dr. Cynthia Goodyer

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.

Genetic study of the metabolic syndrome Researcher: Dr. Pavel Hamet

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.

Genetic study of chronic rhinosinusitis Researcher: Dr. Martin Desrosiers

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.


Understanding the interactions between the environment and the progression of cardiovascular diseases Researcher: Dr. Philip Awadalla

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.


Innovation platform in pediatric scoliosis genomics: from genes to complete diagnostic tests Researcher: Dr. Alain Moreau

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.

Molecular dissection of congenital heart disease in the French Canadian population Researcher: Dr. Gregor Andelfinger

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. 

Prevalence of chronic renal failure in the CARTaGENE cohort Researcher: Dr. François Madore

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.


Studying the risk of bone fracture associated to psychotropic medications Researcher: Dr. Sasha Bernatsky

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.

Development of a platform for the molecular diagnosis of Zellweger syndrome in Quebec Researcher: Dr. Luigi Bouchard

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.

Analysis of the genealogical characteristics of participants from the cohort CARTaGENE Researcher: Dr. Marc Tremblay

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.

Impact of the air pollution on the autoimmune response leading to rheumatoid arthritis Researcher: Dr. Sasha Bernatsky

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.

Study of the accumulation of harmful genetic mutations in spatially expanding populations Researcher: Dr. Laurent Excoffier

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). 

Medical consequences of chromosomal integration of human herpes virus 6 Researcher: Dr. Louis Flamand

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.


Prevalence of chronic renal failure in the CARTaGENE cohort Researcher: Dr. François Madore

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.


Relationship between urinary metabolic profiles and methylmercury exposure Researcher: Dr. Pierre Ayotte

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.