MD, MSc, FRCPC
Pathology and Molecular Medicine
Assistant Professor, Clinical Epidemiology & Biostatistics
Canada Research Chair in Genetic and Molecular Epidemiology
Director, Genetic and Molecular Epidemiology Laboratory
Visiting Scientist, Harvard Medical School
Population Health Research Institute
David Braley Cardiac, Vascular and Stroke Research Institute
237 Barton St. East- C3-103
Tel: (905)527-4322 ext 40356
Assistant: Sue McMillan ext 40377
Education and Professional Standing
Research Fellow, Harvard Medical School, 2009
Medical Biochemist, University of Montreal, 2007
MSc, Human Genetics, McGill University, 2006
MD, University of Montreal, 2002
My main research focus is Genetic and Molecular Epidemiology, whereby I aim to identify genetic determinants of complex disease such as hypertension, coronary artery disease, cerebrovascular disease and other types of chronic disease. Genetic and molecular markers of disease are expected to lead to better understanding, prediction, and ultimately prevention of diseases. I currently have four projects.
Stroke is the third leading cause of death in Canada and a major source of long-term disability. Risk factors such as high blood pressure, diabetes, smoking and abnormal heart rhythm are known to increase chances of getting a stroke. However, in many individuals who develop stroke, particularly young people, we do not find the reason. Stroke is therefore believed to develop through a combination of known risk factors (e.g. high blood pressure) and genetic factors, that make it more likely that a person will have stroke. It is known that genes contribute to the risk of stroke, since stroke occurs commonly in some families. However, very few ‘genes’ that cause stroke have been identified. Understanding the genetic basis of stroke will help provide answers to these important clinical questions.
Heart disease is a leading cause of death in Canada. In addition to risk factors such as smoking and diabetes, increased fats and cholesterol in the blood can lead to narrowing and blockage of the blood vessels to the heart. These fats and cholesterol are carried in the blood in packages called lipoproteins. Increased amounts of one of these packages in the blood, called lipoprotein(a) [Lp(a)], is associated with increased risk of heart and blood vessel disease. However, the real importance of Lp(a) is not yet clear because people of differing genetic ancestry have varying amount and sizes of Lp(a). The size of Lp(a) is determined by our genes. The different sizes of Lp(a) make it difficult to measure in the blood. Another challenge is that smaller size Lp(a) packages lead to larger number of the Lp(a) packages in the blood. At the moment, we are not sure if there is one ‘best’ test to use in all ethnic groups or if it is better to use a combination of tests. The study we propose will analyze Lp(a) in a large number of people from many different ethnic groups, to try to fully understand Lp(a) and its value in helping to predict the risk of developing heart and blood vessel disease.
Pharmacogenetics of antithrombotic drugs
Broadly categorized as antiplatelet and anticoagulation agents, antithrombotic drugs are commonly used for prevention and treatment of venous thromboembolism (VTE), acute coronary syndromes and stroke. Nevertheless, it is increasingly recognized that not all patients benefit equally from drug treatment, with some individuals showing evidence of aspirin “resistance” while others carry genetic variants that modify the platelet inhibitory effect of clopidogrel. Likewise, wide variations in the level of active drug have been noted with the anticoagulation agents dabigatran and apixaban. Such variations result in underdosing some patients (i.e. thrombotic events) and overdosing others (i.e. bleeding events). This project aims to identify the pharmacogenetic determinants of key antithrombotic drugs and evaluate their clinical relevance.
Novel statistical genetics methods
Gene-gene and gene-environment interactions are widely assumed to be an important component of the genetic architecture of complex traits. However, detection of gene-gene and gene-environment interactions using exhaustive search necessarily raises the multiple hypothesis problem. While frequently used to control for experiment-wise type I error, Bonferroni correction is overly conservative and results in reduced statistical power. Our proposed method, Variance Prioritization (VP), selects SNPs having significant heterogeneity in variance per genotype using a pre-determined P-value threshold. We have previously shown that prioritizing SNPs on the basis of heterogeneity in quantitative trait variance per genotype, leads to increased power to detect genetic interactions. This project aims to further refine variance prioritization to improve our ability to identify genetic interactions.
My clinical focus is in cardiovascular prevention, where an individualized approach is used to reduce the risk of cardiovascular disease. I also work in the lipids clinic where I treat patients with rare or complex cases of dyslipidemia.
- Paré G , Ridker PM, Rose L, Barbalic M, Dupuis J, Dehghan A, Bis JC, Benjamin EJ, Shiffman D, Parker AN, Chasman DI. Genome-wide association analysis of soluble ICAM-1 concentration reveals novel associations at the NFKBIK, PNPLA3, RELA and SH2B3 loci. PLoS Genet. 2011 Apr;7(4):e1001374.
- Paré G , Mehta SR, Yusuf S, Anand SS, Connolly SJ, Hirsh J, Simonsen K, Bhatt DL, Fox KAA, Eikelboom JW. Effects of CYP2C19 Genotype on Outcomes of Clopidogrel Treatment. TheNew England Journal of Medicine. 2010 Oct 28;363(18):1704-14.
- Paré G , Anand SS. Mendelian randomisation, triglycerides, and CHD. Lancet. 2010 May 8;375 (9726):1584-6.
- Dubuc G, Tremblay M, Paré G, Jacques H, Boulet L, Genest J, Bernier L, Seidah NG, Davignon J. A new method for measurement of total plasma PSCK9: clinical applications. Journal of Lipid Research. 2010 Jan;51(1):140-9.
- Köttgen A, Glazer NL, Dehghan A, Hwang SH, Katz R, Li M, Yang Q, Gudnason V, Launer LJ, Harris TB, Smith AV, Arking DE, Astor BC, Boerwinkle E, Ehret GB, Ruczinski I, Scharpf RB, Chen YDI, deBoer IH, Haritunians T, Lumley T, Sarnak M, Siscovick D, Benjamin EJ, Levy D, Upadhyay A, Aulchenko YS, Hofman A, Rivadeneira F, Uitterlinden AG, vanDuijn CM, Chasman DI, Paré G, Ridker PM, Kao L, Witteman JC, Coresh J, Shlipak MG, Fox CS. Common Variants in the Gene Encoding Tamm-Horsfall Glycoprotein are Associated with Chronic Kidney Disease Risk. Nature Genetics. In Press. Köttgen A*, Glazer NL*, Dehghan A*, Hwang SJ*, Katz R, Li M, Yang Q, Gudnason V, Launer LJ, Harris TB, Smith AV, Arking DE, Astor BC, Boerwinkle E, Ehret GB, Ruczinski I, Scharpf RB, Ida Chen YD, de Boer IH, Haritunians T, Lumley T, Sarnak M, Siscovick D, Benjamin EJ, Levy D, Upadhyay A, Aulchenko YS, Hofman A, Rivadeneira F, Uitterlinden AG, van Duijn CM, Chasman DI, Paré G, Ridker PM, Kao WH, Witteman JC, Coresh J, Shlipak MG, Fox CS. Multiple loci associated with indices of renal function and chronic kidney disease. The CKDGen Consortium. Nature Genetics. 2009 Jun;41(6):712-7.
- He C, Kraft P, Chen C, Buring JE, Paré G , Hankinson SE, Chanock S, Ridker PM, Hunter DJ, Chasman DI. Genome-wide association studies identify novel loci associated with age at menarche and age at natural menopause. Nature Genetics. 2009 Jun;41(6):724-8.
- Paré G , Chasman DI, Parker AN, Zee RYL, Mälarstig A, Seedorf U, Collins R, Watkins H, Hamsten A, Miletich JP, Ridker PM. Novel Association of CPS1, MUT, NOX4 and DPEP1 with Plasma Homocysteine in a Healthy Population: A Genome Wide Evaluation of 13,974 Participants in the Women’s Genome Health Study. C irculation. Cardiovascular Genetics. 2009 Apr;2(2):142-50.
- Danik JS, Paré G, Chasman DI, Zee RY, Kwiatkowski DJ, Parker AN, Miletich JP, Ridker PM. Multiple Novel Loci Identified in a Genome-Wide Association Study of Fibrinogen in 17,686 women: the Women’s Genome Health Study. Circulation. Cardiovascular Genetics. 2009 Apr 2(2): 134-41.
- Anand SS, Xie CC, Paré G , Montpetit A, Rangarajan S, McQueen M, Cordell H, Keavney B, Yusuf S, Hudson TJ, Engert J. INTERHEART Investigators. Genetic Variants Associated with Myocardial Infarction risk factors in over 8,000 Individuals from Five Ethnic Groups: The INTERHEART Genetics Study. Circulation. Cardiovascular Genetics. 2009 Feb;2(1):16-25, 2009
- Ridker PM, Paré G, Parker AN, Zee RY, Miletich J, Chasman DI. Polymorphism in the CETP Gene Region, HDL Cholesterol, and Risk of Future Myocardial Infarction: Genomewide Analysis among 18,245 Initially Healthy Women from the Women’s Genome Health Study. Circulation. Cardiovascular Genetics. 2009 Feb;2(1):26-33.
- Chasman DI, Paré G, Ridker PM. Population-based genomewide genetic analysis of common clinical chemistry analytes. Clinical Chemistry. 2009 Jan;55(1):39-51.
- Paré G , Chasman DI, Parker AN, Nathan DM, Miletich J, Zee RY, Ridker PM. Novel Association of HK1 with Glycated Hemoglobin in a Non-Diabetic Population: A Genome Wide Evaluation of 14,618 Participants in the Women's Genome Health Study. PLoS Genetics. 2008 Dec;4(12): e1000312.
- Chasman DI, Paré G, Zee RYL, Parker AN, Cook NR, Buring JE, Kwiatkowski DJ, Rose LM, Smith JD, Williams PT, Rieder MJ, Rotter JI, Nickerson DA,Krauss RM, Miletich JP, Ridker PM. Genetic loci associated with plasma concentration of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, and Apolipoprotein B among 6382 white women in genome-wide analysis with replication. Circulation. Cardiovascular Genetics . 2008 Oct;1(1):21-30.
- Paré G , Chasman DI, Kellogg M, Zee RYL, Rifai N, Badola S, Miletich J, Ridker PM. Novel Association of ABO Histo-Blood Group Antigen with Soluble ICAM-1: Results of a Genome-Wide Association Study of 6,578 Women. PLoS Genetics. 2008 Jul;44(7): e1000118.
- Ridker PM, Paré G, Parker A, Zee RY, Danik JS, Buring JE, Kwiatkowski D, Cook NR, Miletich JP, Chasman DI. Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study. American Journal of Human Genetics. 2008 May;82(5): 1185-92.
- Serre D, Montpetit A, Paré G, Engert JC, Yusuf S, Keavney B, Hudson TJ, Anand S. Correction of population stratification in large multi-ethnic association studies. PLoS ONE. 2008 Jan 2; 3(1):e1382.
- Paré G , Serre D, Brisson D, Anand S, Montpetit A, Tremblay G, Engert JC, Hudson TJ, Gaudet D. Genetic analysis of 103 candidate genes for coronary artery disease and associated phenotypes in a founder population reveals a new association between endothelin-1 and high-density lipoprotein cholesterol. American Journal of Human Genetics. 2007 Apr;80(4):673-82.