OMB No. 0925-0001 and 0925-0002 (Rev. 10/2021 Approved Through 09/30/2024) BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FIVE PAGES. NAME: GUILLAUME PARE, MD, M.Sc., FRCP(C) eRA COMMONS USER NAME (credential, e.g., agency login): PAREGU POSITION TITLE: Director, Genetic and Molecular Epidemiology Laboratory; Professor of Medicine, McMaster University EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.) DEGREE INSTITUTION AND LOCATION (if applicable) Start Date MM/YYYY Harvard Medical School, Boston, MA Completion Date MM/YYYY 2007 2009 FIELD OF STUDY McGill University, Montreal, Canada M.Sc. 2005 2006 Human Genetics Research Fellow University of Montreal, School of Medicine, Montreal, Canada University of Montreal, School of Medicine, Montreal, Canada A. Personal Statement 2002 2007 Medical Biochemistry Residency MD 1997 2002 Medicine Guillaume Paré is Director of the Clinical Research Laboratory and Biobank (CRLB) – Genetic and Molecular Epidemiology Laboratory (GMEL). He is also Deputy Director of the Thrombosis and Atherosclerosis Research Institute (TaARI), a Professor of Pathology and Molecular Medicine, a Professor in the Department of Health Research Methods, Evidence and Impact, and a University Scholar at McMaster University. A medical biochemist with board certification from the Royal College of Physicians and Surgeons of Canada, Dr. Paré completed a Master’s in Human Genetics at McGill University under the supervision of renowned geneticist Thomas Hudson. He further trained in genetic epidemiology with Paul Ridker at Harvard Medical School. His clinical interests are centered on lipoprotein disorders, obesity and cardiovascular disease prevention, with research interests in cardiovascular genetics, biomarker development and pharmacogenomics. Dr. Paré’s research combines highthroughput biomarker screens with genetics, bioinformatics and epidemiology to identify novel cardio-metabolic biomarkers. He has published more than 250 original contributions in peer-reviewed journals, all related to his research program in cardiovascular disease and genetics. These include first or last authored articles in the NEJM, Lancet, Circulation, EHJ, Stroke, JACC, PloS Genetics, Circulations Genomics and Precision Medicine and AJHAG. His work has been sited over 35,000 times with a corresponding h-index of 80. He was inducted to the Royal Society of Canada’s College of New Scholars, Artist and Scientists in 2018. B. Positions and Honors Positions 2019-pres. Professor, Dept. of Pathology and Molecular Medicine; Joint app’t, CE&B 2014-2019 Associate Professor, Dept. of Pathology and Molecular Medicine; Joint app’t, CE&B 2009-pres. Medical Biochemist- Hamilton Regional Laboratory Medicine Program, FHS, McMaster U. 2009-pres. Director, Genetic and Molecular Epidemiology Laboratory, McMaster University 2009-2014 Assistant Professor, Dept. of Pathology & Molecular Medicine; Joint app’t, HEI (formerly CE&B), McMaster University 2009-2012 Visiting Scientist, Harvard Medical School Affiliations (McMaster University) 2019-2024 Associate Member, Department of Medicine. FHS 2018 Jan- Member, Global Health Graduate Studies Program 2017 Oct- Member, Biochemistry and Biomedical Sciences Graduate Studies Program Other Experience and Professional Memberships 2020-pres Committee Member, Provincial Advisory Committee (PAC) for the Canadian Statistical Sciences Institute (CANSSI) 2019-pres Committee Member, American Heart Association (AHA) – GPM (Genomic and Precision Medicine) & EPI Molecular Determinants of Cardiovascular Health Committee of the Council on Genomic and Precision Medicine 2018-pres Medical Biochemistry Residency Program Director, McMaster University 2017-pres Member, European Association for the Study of Diabetes 2015-pres Member, American Heart Association 2014-pres Editorial Board Member– Arteriosclerosis, Thrombosis and Vascular Biology 2014-pres Editorial Board Member– Canadian Journal of Cardiology 2014-2016 International Genetic Epidemiology Society – annual meeting planning committee member 2013-2015 International Stroke Genetics Consortium– Scientific Steering Committee member 2012 Guest Editor- PLoS Genetics 2012 International Editorial Board Member- Journal of the Royal Society of Medicine Cardiovascular Disease 2010-pres Statistical Reviewer, European Heart Journal 2010 Associate Editor, BMC Medical Genetics 2005-pres Member, American Society of Human Genetics (ASHG) Additional Contributions: Dr. Paré is frequently invited to review manuscripts (Nature Genetics, PLoS Genetics, American J Human Genetics, NEJM, JAMA, EJH, Circulation, etc.) and grants by leading national and international scientific organizations, such as the Canadian Institutes for Health Research, Wellcome Trust (UK), Michael Smith Foundation (Canada), National Institutes of Health (USA), Agence Nationale de Recherche (France) and Netherlands Organization for Scientific Research. Dr. Paré is also recognized by the Canadian scientific community as an expert in cardiovascular genetics and is a member of the Editorial board of ATVB and the Canadian Journal of Cardiology. Finally, Dr. Paré has given 225 lectures since 2009 – locally, regionally, nationally, and internationally, spanning 25 countries. He is a member of the Committee on Scientific Sessions Program of the AHA. Honors and Aw ards: 2021 Canadian Association of Medical Biochemists, Research Achievement Award 2019 Excellence in Graduate Studies Supervision Award, McMaster University 2018 AHA selected paper (Theriault et al., Circ Genom Precis Med 11:e001849, 2018) as one of the ‘Top 10’ Advances in Cardiovascular Research in 2018’ 2018 Royal Society of Canada’s College of New Scholars, Artists and Scientists; inducted Nov.2018 2018-2022 University Scholar Prize Award – McMaster University 2015 McMaster University – A celebration of Research Excellence recognition 2014-2019 Ontario Ministry of Economic Development & Innovation- Early Researcher Award (ERA) 2013 Mrs. Asha Verma Memorial Translational Lectures in Cardiovascular Medicine Award- SMH- TO. 2012 CIHR Institute of Genetics Maud Menten New Principal Investigator Finalist Prize- MMC- 124494 2010 CIHR Institute of Genetics, Maud Menten New Principal Investigator Prize (Clinical)- MMC- 108725 2010 Canada Research Chair, Genetic and Molecular Epidemiology 2009 4th Annual Canadian Statistical Genetics Meeting, Best trainee oral presentation 2007 School of medicine, University of Montreal, Dean’s honor list for academic excellence 2007 Fonds de la recherche en santé du Québec (FRSQ), Fellowship scholarship 2005 Annual research meeting of University of Montreal Health Center, Best poster presentation 2004 Annual meeting of the Quebec Association of Medical Biochemists, Best scientific presentation 2002 School of Medicine, University of Montreal, Dean’s honor list for academic excellence 2000 School of Medicine, University of Montreal, Best undergraduate research project C. Contributions to Science Research Contributions: Development of methodologies in genetic epidemiology Finding gene-gene and gene-environment interactions is a challenge in genetic epidemiology and my group developed a statistical method to identify such interactions (Paré et al. PLoS Gen 2010; Deng et al. Eur J Hum Gen 2014). We also developed an approach to test regional genetic associations (Paré et al. PLoS Gen 2015) that we extended to estimate polygenic regional variance from summary statistics (Paré et al. Sci Rep 2016) and machine-learning methods to determine polygenic risk scores (Paré et al. Sci Rep 2017). Such methods facilitated the prediction of EOCAD and the AHA named our study one of 2018’s top 10 most influential advancements in heart and stroke research (Theriault et al. Circ Genom Precis Med 2018; please see: https://tinyurl.com/qreswc3). We pioneered the use of Mendelian randomization (MR) to show that diabetes is causally involved in CAD (Ross et al. EHJ 2015), and to identify biomarkers and drug targets for ischemic stroke (Chong et al. Circ 2019), biomarkers linking metabolically-favorable adiposity with type 2 diabetes risk (Pigeyre et al. Diabetes Care 42 2019), and show that HER2 is a causal mediator of the protective effect of ACE inhibitors on kidney function (Sjaarda et al. JASN 2018). We also developed a reverse MR method to identify markers of CKD (Mohammadi- Shemirani et al. Clin Chem 2019) and methods to explore relationships between genetic ancestry and biomarker levels (Sjaarda et al. AJHG 2020). Identification of genetic determinants of cardiovascular diseases We identified genetic determinants of lipoprotein concentrations (Paré et al. AJHG 2007; Paré et al. Circ 2019), glucose metabolism (Paré et al. PLoS Gen 2008), homocysteine concentrations (Paré et al. Circ Gen 2009), and markers of inflammation (Paré et al. PLoS Gen 2011). I belonged to studies detailing the role of genetics in CVDs (Ridker et al. Circ Gen 2009; Paynter et al. JAMA 2010) and consortia discovering loci associated with CAD (Zhao et al. Nat Genet 2017; Patel et al. Circ Genom Precis Med 2019), stroke (MEGASTROKE, Nat Commun 2018; ISGC, Neurology 2019; Nat Genet 2018; Lancet Neurol 2016), and atrial fibri lation (Roselli et al. Nat Genet 2018). More recently we have described the role of ACE2 in CVD (Lancet 2020). Pharmacogenetics of antiplatelet and anticoagulant agents Clopidogrel is used to reduce the risk of heart attack and stroke. Individuals with a CYP2C19 loss-of-function (LOF) allele have an attenuated benefit from clopidogrel, leading to an FDA warning. Our studies of acute coronary syndrome and atrial fibri lation showed that the negative effects of LOF alleles do not apply to all populations. Rather, the CYP2C19 gain-of-function allele may be equally or more important than the LOF allele in specific populations (Paré et al. N Engl J Med 2010; Paré et al. Circ Gen 2012). We also described a pharmacogenetic association between CES1 and bleed risk with the anticoagulant, dabigatran (Paré et al. Circ 2013), and described an association between a COX-2 variant and its effect on aspirin (Ross et al. EHJ 2014). Training of High Qualified Personnel: In the last 13 years Dr. Paré has mentored 132 trainees. He has been directly involved in the training of 15 Postdoctoral Fellows, 9 PhD candidates (3 current), 13 MSc students (5 current), and 52 Undergraduate students (11 current). He supervises Medical Residents in Lipid Clinics on an ongoing basis. 12 of his undergraduate students have been accepted or have completed Medical School, 1 completed School of Dentistry, and 5 pursued PhD studies. He has also supervised 8 international students (1 current), and served as Committee Member for numerous MSc and PhD students. List of Publications from US National Library of Medicine; National Institutes of Health- PubMed.gov https://www.ncbi.nlm.nih.gov/myncbi/guillaume.pare.1/bib liography/public/ Citations of Peer-Reviewed Articles (using Google Scholar)- since 2009 *Note- may include self-citations h-index Number of Publications (includes Peer-Reviewed Journal Articles, Accepted/ In Press Journal Articles, Editorials & Commentaries, Book Chapters) 37,380 80 278 Below are some selected publications. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Mohammadi-Shemirani P, Chong M, Narula S, Perrot N, Conen D, Roberts JD, Thériault S, Bossé Y, Lanktree MB, Pigeyre M, Paré G.- ‘Elevated Lipoprotein(a) and Risk of Atrial Fibrillation: An Observational and Mendelian Randomization Study.’ J Am Coll Cardiol. 2022 Apr 26;79(16):1579-1590. doi: 10.1016/j.jacc.2022.02.018.PMID: 35450575 Chong M, Mohammadi-Shemirani P, Perrot N, Nelson W, Morton R, Narula S, Lali R, Khan I, Khan M, Judge C, Machipisa T, Cawte N, O’Donnell M, Pigeyre M, Akhabir L, Paré G.- ‘GWAS and ExWAS of blood mitochondrial DNA copy number identifies 71 loci and highlights a potential causal role in dementia.’ Elife. 2022 Jan 13. 11: e70382. doi: 10.7554/eLife.70382. PMID: 35023831 Chong M, Langhorne P, Narula S, Morton RW, Judge C, Akhabir L, Cawte N, Pathan N, Lali R, Mohammadi-Shemirani P, Shoamanesh A, O’Donnell M, Yusuf S, Langhorne P, Paré G. Mitochondrial DNA copy number as a marker and mediator of stroke prognosis: Observational and Mendelian Randomization analyses.’ Neurology. 2021 Dec.8. PMID: 34880091 Machipisa T, Chong M, Muhamed B, Chishala C, Shaboodien G, Pandie S, de Vries J, Lian N, Joachim A, Daniels R, Ntsekhe M, Hugo-Hamman CT, Gitura B, Ogendo S, Lwabi P, Okello E, Damasceno A, Novela C, Mocumbi AO, Madeira G, Musuku J, Mtaja A, Elsayed A, Elhassan HHM, Bode-Thomas F, Okeahialam BN, Zuhlke LJ, Mulder N, Ramesar R, Lesosky M, Parks T, Cordell HJ, Keavney B, Engel ME, Paré G. Association of novel locus with rheumatic heart disease in black African individuals: Findsing from the RHDGen Study. JAMA Cardiology. 01 Sep 2021;6(9):1000-1011. PMID: 34106200 Lali R, Chong M, Omidi A, Mohammadi-Shemirani P, Le A, Cui E, Paré G. Calibrated rare variant genetic risk scores for complex disease prediction using large exome sequence repositories. Nat Commun. 2021 Oct 6;12(1):5852. PMID: 34615865 Narula S, Yusuf S, Chong M, Ramasundarahettige C, Rangarajan S, Bangdiwala SI, van Eikels M, Leineweber K, Wu A, Pigeyre M, Paré G. (2020) Plasma ACE2 and risk of death or cardiometabolic diseases: a case-cohort analysis. Lancet. 396(10256):968-976 Sjaarda J, Gerstein HC, Kutalik Z, Mohammadi-Shemirani P, Pigeyre M, Hess S, Paré G. Influence of Genetic Ancestry on Human Serum Proteome. (2020) Am J Hum Genet.106(3):303-314 Chong M, Sjaarda J, Pigeyre M, Mohammadi-Shemirani P, Lali R, Shoamanesh A, Gerstein H, Paré G. (2019) Novel drug targets for ischemic stroke identified through Mendelian randomization analysis of the blood proteome. Circulation.140(10):819-830 Paré G, Çaku A, McQueen M, Anand SS, Enas E, Clarke R, Boffa MB, Koschinsky M, Wang X, Yusuf S, on behalf of the INTERHEART Investigators. (2019) Lipoprotein(a) levels and the risk of myocardial infarction among seven ethnic groups. Circulation. 139(12):1472-1482 Sjaarda J, Gerstein HC, Chong M, Yusuf S, Meyre D, Anand S, Hess S, Paré G. (2018) Blood CSF1 and CXCL12 as causal mediators of coronary artery disease. J Am Coll Cardiol. 72(3):300-310 D. Additional Information: Research Support Ongoing Research Support (as PI) (PI: Paré, G) Canada Foundation for Innovation- John R. Edwards Leader Fund (CFI-JELF) High throughput whole genome sequencing for improved disease risk prediction (PI: Paré, G) HSFC 2019/2010 GIA Polygenic risk scores for the prediction of early coronary artery disease (PI: Paré, G) Canadian Institutes of Health Research, Project Grant Spring 2018 2019-2024 04/01/2019-03/31/2022 09/01/2018-08/31/2022 Risk prediction of cardio-metabolic diseases using an integrated genomic-proteomic approach 04/01/2018-03/31/2021 (PI: Paré, G) Heart and Stroke Foundation of Canada 2017/2017 GIA An integrated genomic-biomarker approach for the discovery of novel causal mediators of cardio- metabolic diseases (PI: Paré, G) 04/01/2018-03/31/2022 Ontario Ministry of Economic Development and Innovation- Early Researcher Award (MEDI-ERA) Developing novel blood tests to predict complications of diabetes Brief Description: Salary support for a post-doc in genetic epidemiology (PI: Paré, G) Population Health Research Institute (PHRI) Developing novel blood tests to predict complications of diabetes Brief Description: Salary support for a post-doc in genetic epidemiology Completed Research Support (as PI; last 4 years) (PI: Paré, G) Roche Diagnostics 04/01/2018-03/31/2022 09/2020-08/2021 Post discharge after surgery Virtual Care with Remote Automated Monitoring technology (PI:Paré, G) Heart and Stroke Foundation of Canada 04/2018-03/2021 An integrated genomic-biomarker approach for the discovery of novel causal mediators of cardiometabolic diseases (PI:Paré, G) Bayer (Global) NAVIGATE – ESUS Biomarkers (PI:Paré, G) Bayer (Global) COMPASS Biomarkers 01/2018-12/2020 01/2018-12/2020 (PI: Paré, G) 09/01/2017-08/31/2019 Canadian Institutes of Health Research, Personalized Health Catalyst Grant Machine-learning algorithms for gene score prediction of cardio-metabolic traits (PI: Paré, G) 11/01/2014-09/30/2019 CRC – Renewal File No.950-230055 Canada Research Chair in Genetic and Molecular Epidemiology; Tier 2- Renewal (PI: Paré, G) 07/01/2015-06/30/2018 Heart and Stroke Foundation of Canada Genetic determinants of early stroke- A population study from INTERSTROKE (PI: Paré, G) CIHR Project Scheme: 2016 1st Live Pilot Transitional funding Genetic and molecular determinants of early onset coronary artery disease (PI: Paré, G) CIHR- Industry –Partnered Collaborative Research, Funding Ref.No. 125794 07/01/2016-06/30/2017 04/01/2013-03/31/2017 Integration of clinical, biomarker, and genetic data for prediction of adverse outcomes in diabetes