Our Research

The Human Genomics Laboratory investigates the genetic and molecular basis of the response to a physically active lifestyle, with an emphasis on cardiorespiratory endurance, cardiovascular disease, and type 2 diabetes risk factors, as well as the genetic and molecular background of obesity and abdominal obesity and their comorbidities. It relies primarily on the resources of the HERITAGE Family Study, the Québec Family Study (QFS) , the CARDIA Longitudinal Study, the Swedish Obese Subjects (SOS) Study, the GENATHLETE Study, and the HYPGENE Study. The scientists of the Human Genomics Laboratory have also developed a network of collaborative laboratories from multiple countries. 

HERITAGE Family Study

One project focused on genotype-exercise interactions is the HERITAGE Family Study. The aim of the HERITAGE Family Study is to document the cardiovascular and metabolic responses to endurance exercise training and the contribution of genetic factors to the concomitant response of cardiovascular disease and type 2 diabetes risk factors.

The HERITAGE Family Study has been funded by National Heart, Lung, and Blood Institute grants HL-45670,

HL-47323, HL-47317, HL-47327, and HL-47321.

Phase 1 of HERITAGE (1992 to 1997) was devoted to the recruitment of White and Black families and to extensive testing of all individuals before and after a 20-week laboratory-controlled and fully standardized exercise program. Five centers were involved: University of Minnesota (PI: Arthur Leon), University of Arizona and then University of Indiana (PI: James Skinner), University of Texas at Austin (PI: Jack Wilmore), Washington University (PI: D.C. Rao), and Laval University in Quebec City (PI: Claude Bouchard). Washington University served as the Data Coordinating Center (PI: Rao). Claude Bouchard, leader of the entire project, served as the chair of the HERITAGE Steering Committee and as the coordinator of the core facilities (lipid core, steroid core, hormone core, cell lines core) located at Laval University in Quebec City. In Phase 2 (1997 to 2001), the HERITAGE database was used extensively to document the range of human variation in the response to regular exercise, level of familial aggregation and heritability, and differences in response by age, gender, and race. A panel of pre-selected markers in candidate genes was used to investigate possible associations with the baseline and response levels for a variety of phenotypes. A first genome-wide scan with a panel of about 300 markers was undertaken for several baseline and response phenotypes. Phase 3 (2001 to 2005) dealt with the genetic epidemiology of training-induced changes in major cardiovascular disease risk factors, with an emphasis on possible Black and White differences. Targeted cardiovascular disease and type 2 diabetes risk factors and their responses to regular exercise were investigated, with an emphasis on Black and White differences. Microarray studies of vastus lateralis skeletal muscle mRNA obtained in a subset of 78 HERITAGE participants have been undertaken, with the goal of comparing the profile of those who did not improve and those who almost doubled their insulin sensitivity in response to regular exercise. More refined genome-wide linkage scans were completed by the end of Phase 3 with a denser panel of markers (650 microsatellites) and more powerful analytical strategies. Phase 4 (2006 to 2013) focused on a genome-wide association exploration of the response to regular exercise of cardiorespiratory fitness and several metabolic traits.

More than 160 papers have been published based on the data of the HERITAGE Family Study and are listed on the HERITAGE website.


Québec Family Study

The Québec Family Study (QFS) was initiated in 1978 when the principal investigator (C Bouchard) was on faculty at Laval University in Quebec City, Canada. The study has been divided into three phases. Participants in QFS are of French descent living within about 50 miles (80 km) around Quebec City. They were mainly recruited through the media and referrals from other participants and colleagues.

Recruitment and Sample Size

During Phase 1, from 1978 to 1982, data were gathered on 1,630 subjects, including 727 parents ranging in age from 30 to 59 years of age and 903 offspring, 8 to 26 years old. None were diabetic or treated for cardiovascular disease. These families were randomly ascertained with regards to obesity. The average socioeconomic status of these families based on the occupation of the father was comparable to the general French-Canadian population. In addition to traditional nuclear family members (ie, parents and their singleton offspring), there were twins, adoptees, cousins, and foster parents.

During Phase 2 of the study, which began in 1992, 385 subjects from 105 Phase 1 families agreed to be measured for a second time after an average follow-up period of 12 years, and new families with one or more obese members were recruited, thus, 372 new subjects from 74 families were incorporated in the study. Only families with biological offspring were incorporated into this phase.

Phase 3 of the study started in 1997 with 5-year follow-up measurements of families tested in Phase 2 and with recruitment of new families with obese probands.  At the end of Phase 3, the QFS cohort included more than 2,000 subjects from more than 500 families. Among them, phenotype and DNA are available on 930 subjects belonging to 292 nuclear families.  There was a total of 158 families with 511 subjects who had completed the measurement protocols of the follow-up periods.


An overview of the phenotypes available on all or almost all QFS subjects is given below. Subjects of QFS were also enrolled in ancillary studies.

Concomitant and Behavioral Variables: Medical history: physical examination, number of pregnancies, cause of death, familial history of disease, smoking, consumption of alcohol, medication, sleep habits, personal income, family income, level of education, occupation, age at menarche, menstrual status (pre- or post-menopausal), hormone replacement therapy and others.

Body Fat and Regional Fat Distribution: Body weight, body mass index (BMI), body composition (percent body fat, fat mass, fat free mass) assessed by underwater weighing, skinfold thicknesses at 8 different sites, waist circumference, hip circumference, waist to hip ratio, abdominal fat (total, subcutaneous and visceral) assessed by an L4-L5 CT scan.

Energy Intake and Physical Activity Level: 3-day dietary record for assessment of total energy, macronutrient (carbohydrate, lipid and protein) and micronutrient intakes. History of food habits. Eating behaviors questionnaire (TFEQ).  3-day activity record and physical activity history.

Energy Metabolism and Fitness: Resting metabolic rate and substrate oxidation rate, measurements of sitting, standing and exercise metabolic rates.  Submaximal exercise capacity.

Risk Factor Profile: Resting blood pressure, resting heart rate, plasma levels of glucose and insulin in a fasting state and following an oral glucose tolerance test; fasting plasma levels of lipids, lipoproteins and apolipoproteins (CHOL, TG, VLDL-CHOL, LDL-CHOL, VLDL-TG, LDL-TG, HDL-CHOL, HDL2-CHOL, HDL3-CHOL, apoA1, apoB, VLDL-apoB, LDL-apoB, Lp(a), proportion of small dense LDL phenotype, LDL and HDL particle size, cholesteryl ester transfer protein).

Ancillary Studies: Several phenotypes have been obtained on subsets of the QFS cohort in the context of a number of ancillary studies. These measurements include: echocardiographic assessment, isometric strength measurements, adipose tissue biopsies and morphological and biochemical studies, vastus lateralis muscle biopsies with fiber type determination and biochemical studies, cold tolerance tests, catecholamine studies, panel of steroid assays, pulmonary ventilation tests, etc.


The study was conceived by Claude Bouchard. The first phase was undertaken under the leadership of

Drs. Claude Bouchard, Angelo Tremblay, and Claude Allard. Other investigators who joined the leadership of QFS over time include Drs. Jean-Pierre Després, Germain Thériault, Louis Pérusse, Jean-Aime Simoneau, and Yvon Chagnon. The day-to-day management of the project was the responsibility of Guy Fournier and Lucie Allard. Claude Leblanc provided the computer and data management support, Gilles Bouchard the equipment maintenance and calibration, and Monique Chagnon the clinical chemistry and genetic laboratory supervision. Many other scientists contributed to the project, including the following: Jean Bergeron, Nathalie Bergeron, Ingrid Borecki, Charles Couillard, Yves Deshaies, France Dionne, Denis Joanisse, Benoit Lamarche, Simone Lemieux, Paul Lupien, Andre Marette, Pascale Mauriege, Sital Moorjani, Andre Nadeau, Michael Province, DC Rao, Treva Rice, Andre Tchernof, Marie-Christine Thibault, Marie-Claude Vohl, and John Weisnagel.

Grant Support

The Québec Family Study began in 1978 with funding from the Fonds pour la formation de chercheurs et l'action concertée du Québec (FCAC), Fonds de la Recherche en Santé du Québec (FRSQ), Fonds pour la formation de Chercheurs et l’Aide à la Recherche (FCAR), and the Haut-Commissariat à la Jeunesse, aux Loisirs et aux Sports of Québec (HCJLS), Conseil pour la recherche en santé du Québec (CRSQ), Ministère du loisir, de la chasse et de la pêche du Québec (MLCP), and from Health and Welfare Canada. From 1989 to 1992, Phase 2, the Québec Family Study was funded by an operating grant from the Medical Research Council of Canada (MA-10499). In Phase 3, from 1992 to 1997, the study was funded by a Program Grant from MRC (PG-11811) and from 1998 to 2001 by a Group Grant from the same Council. Additional funding has been received over the years from the Heart and Stroke Foundation, the Canadian Diabetes Association, the Canadian Fitness and Lifestyle Research Institute, and other agencies as well. More recently, QFS has been funded by the Canadian Institute for Health Research.

More than 270 publications have been based on QFS data.


CARDIA Fitness Study

The Coronary Artery Risk Development in Young Adults (CARDIA) study is based on a cohort of 5,116 black and white women and men, age 18-30 years, who were recruited and examined, during 1985-1986, in four urban areas: Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota, and Oakland, California. The initial examination included carefully standardized measurements of cardiovascular risk factors as well as assessments of psychosocial, dietary, and exercise-related characteristics that might influence them, or that might be independent risk factors.

Cardiovascular risk factors monitored over time include such variables as homocysteine levels, CRP and interleukin-6, blood pressure, lipid levels, insulin, lung function, BMI, etc. Some of the many variables tested for association with various cardiovascular risk factors include mood (such as depression or aggression), socioeconomic and employment status, race or gender, diet, physical activity level, alcohol use or smoking, sleep duration, etc.

The Human Genomics Laboratory is investigating associations between cardiorespiratory fitness and DNA sequence variants in several candidate genes, including ACE, AGT, BDKRB2, EDN1, GNB3, NOS3, and PPARGC1A, as well as fitness-by-genotype interaction effects on changes in blood pressure and on risk of hypertension.

Members of the Human Genomics Laboratory have published the following papers based on CARDIA data:


Swedish Obese Subjects (SOS) Study
The primary aim of the entire SOS project has been to examine the effect of bariatric surgery on overall mortality in obese subjects. This aim was achieved with a NEJM publication in 2007 (29% risk reduction). The secondary aims were to examine the effects of bariatric surgery on diabetes type 2, myocardial infarction and stroke. Other goals were to study the effects of bariatric surgery on health related quality of life, health economics and cardiovascular risk factors, and to elucidate genetics questions regarding obesity.

SOS is an ongoing controlled intervention trial of obese subjects in Sweden. A prospective rather than randomized design was used due to postoperative mortality rates up to 5%  in the 1980’s. The study was undertaken at 480 primary health care centers and 25 surgical departments. Incident disease data was obtained from questionnaires, lab examinations, and cross-checks of the SOS database against the Swedish cause of death, hospital discharge and cancer registers, with DNA extracted from all individuals at baseline. The outcomes in a surgically treated group (N=2010) were then compared with those of a contemporaneously matched, conventionally treated control group (N=2037) over 20 years. Two substudies in the SOS project, the SOS Reference Study (n=1137 randomly selected individuals) and the SOS Sib-pair Study (total n=750, families and sib-pairs) provided, respectively, a cohort of Swedish lean controls for genetic association studies and a cohort of 160 BMI-discordant sib pairs (BMI difference ≥ 10 units) and their families (total n=750). The phenotyping was extensive and included RNA transcript levels in adipose tissue.

Since the study began in 1987, SOS has resulted in many peer-reviewed original articles, reviews, and book chapters.  Compared to conventional treatment in the control group, bariatric surgery resulted in large and well-maintained weight losses over 10 and 15 years, reduced the 10 year incidence of diabetes by 75%, overall mortality by 29%, and cancer incidence in women by 42%. Several studies in collaboration with PBRC and other international groups have been very successful.  Currently, up to 20-year effects of bariatric surgery on diabetes type 2, myocardial infarction, and stroke have been examined. SOS has proven that bariatric surgery is an outstanding option in the treatment of obesity resulting in reduced morbidity and mortality and in markedly improved health-related quality of life.  Currently, the Human Genomics laboratory is working with SOS data on SNPs and candidate genes to investigate the role of genetic differences in weight loss, weight maintenance, and associated changes in metabolic risk factors.

Members of the Human Genomics Laboratory have been involved in 20 publications based on SOS.



Low cardiorespiratory fitness is the single most powerful predictor of cardiovascular events and cardiovascular death. We know that regular exercise has on average significant, positive effects on all indicators of cardiorespiratory fitness. However, there are substantial fractions of the adult population that experience only very minor increases or no increases at all in cardiorespiratory fitness despite the fact that compliance to the exercise program was not a factor. There is a need for a better understanding of the biology underlying the ability to attain a high level of cardiorespiratory fitness because of its extraordinary health implications. One approach to meeting this goal is to identify the genes exhibiting DNA sequence variation strongly associated with very high levels of cardiorespiratory fitness. The identification of these genes and DNA variants would illuminate the underlying biology and could result in improved methods or interventions to ameliorate cardiorespiratory fitness, as well as dietary or pharmacological approaches.

The GENATHLETE case-control study explores the contribution of genetic variation to the elite endurance athlete status. The subjects and controls are all Caucasian males recruited from Germany, North America, and Finland. The athletes represent several endurance sports (cross-country skiers, biathletes, long-distance runners, and road cyclists), and all athletes are required to have a measured VO2max, the gold standard for cardiorespiratory fitness, of 75 ml/kg/min or better. GENATHLETE is being used to test the potential contribution of DNA sequence variants to elite athlete status.

To complement GENATHLETE, in collaboration with Professor Yannis Pitsiladis from the University of Glasgow and colleagues from Madrid and Tokyo, we have established a consortium of laboratories from Japan, Scotland, Spain, China, Kenya, and Ethiopia to bring together resources from multiple populations of elite endurance athletes. These laboratories have all accumulated over the years data on large numbers of highly trained, world-class elite endurance athletes and sedentary matched controls. These cohorts include the following approximate numbers of subjects.


Number of Athletes

Number of Controls










Kenya and Ethiopia






We are taking advantage of a genomic exploration undertaken in the GENATHLETE cohort with the CardioMetabochip panel (140,000 polymorphic markers) and of a GWAS performed on the Japanese samples of athletes and controls to define a robust panel of markers to be genotyped across all cohorts of Caucasian, Asian, and African athletes and controls.

The project is conducted by the following investigators:

  • Claude Bouchard, Tuomo Rankinen, and Mark Sarzynski from the Human Genomics Laboratory
  • Yannis Pitsiladis and Guan Wang from the University of Glasgow, UK
  • Alejandro Lucia, Universidad Europea de Madrid, Spain
  • Noriyuki Fuku, Motohiko Miyachi, Haruka Murakami, Tokyo Metropolitan Institute of Gerontology and National Institute of Health and Nutrition, Japan
  • Bernd Wolfarth, Technical University Munich, Germany
  • Louis Perusse, Laval University, Quebec, Canada

Publications from this project include:



The HYPGENE case-control study drew from the Aerobics Center Longitudinal Study (ACLS) database to focus on hypertension, beginning in 2000. Blood samples were banked for HYPGENE subjects. Eligibility requirements for HYPGENE subjects included resting blood pressure 134/86 mm Hg or less at their first clinic visit. Individuals with diagnosed hypertension or other chronic disease (cardiovascular disease, stroke, type I or type II diabetes mellitus, cancer, arthritis, etc.) as well as those with any blood pressure affecting medication at the first clinic visit were excluded. All eligible subjects were required to have at least two clinic visits with a minimum of 2 years apart.

From this group, cases (n=629) and controls (n=605) were selected. Cases were defined as subjects who developed hypertension during the follow-up two years later. The controls were selected randomly using a sex-specific frequency matching protocol within a 5-yr baseline age strata, allowing up to 20% oversampling within the sex-by-age strata. This provided cases and controls of similar age at baseline (first clinic visit).

Rankinen et al. examined the relationship of hypertension, BMI, and cardiorespiratory fitness. Over an average follow-up of 8.7 years, 629 of the subjects developed hypertension. Age-matched controls were drawn from those who did not develop hypertension. Analyses of associations for BMI and cardiorespiratory fitness were adjusted for age, sex, follow-up time, and BMI or fitness. Cardiorespiratory fitness was the strongest predictor of the hypertension risk, with each maximal metabolic equivalent unit being associated with a 19% lower risk (95% confidence interval [95% CI], 12-24%). Each baseline BMI unit was associated with a 9% higher hypertension risk (95% CI, 4-13%) (Rankinen et al, 2007).

The HYPGENE cohort has also been studied for associations between the Rho-associated kinase (ROCK) 2 gene and hypertension. A haplotype defined by four SNPs (rs965665, rs10178332, rs6755196, rs10929732) was recessively associated with a lower risk of hypertension (p=0.002): homozygotes for the minor alleles had 60% to 85% lower risk of hypertension than the carriers of the common allele. The associations were independent of baseline age, cardiorespiratory fitness, body mass index, sex, and follow-up time (Rankinen et al 2008).  This strongly suggests that a major haplotype block at the ROCK2 locus is recessively associated with a lower risk of hypertension.

The HYPGENE study was supported by the National Heart, Lung, and Blood Institute Grant HL-069870. The proiect is inactive at this time.

Publications based on HYPGENE data include: