Digging for translational gold: Multi-omics approach to cardio-metabolic traits

Guillaume Paré, MD, MSc, FRCPc
Professor 
Department of Pathology & Molecular Medicine

Senior Scientist
Population Health Research Institute

Deputy Director
Thrombosis and Atherosclerosis Research Institute

Director
Genetic and Molecular Epidemiology Laboratory - Clinical Research Laboratory and Biobank
McMaster University & Hamilton Health Sciences
 

This conference is hosted by Jean-François Côté, PhD. This conference is part of the 2024-2025 IRCM conference calendar.

About this conference
Despite recent advances in acute diagnosis and treatment of cardio-metabolic diseases (CMD), the development of new blood biomarkers for risk stratification has been slow. The majority of reported biomarker-disease associations fail to enter clinical practice due to their inabilities to discriminate risk, or more importantly, due to a lack of evidence that they represent causal associations with risk of disease. This latter pitfall is particularly damning as the lack of causality prevents conclusions about the benefit of interventions to decrease putative risk factors, and also make the disease association itself vulnerable to known or unknown confounders. Distinguishing modifiable, causal mediators from the many biomarkers that are statistically linked to CMDs is a primary challenge in molecular epidemiology. Even the strongest epidemiological associations do not imply causation, making the discovery of modifiable risk factors difficult. However, truly causal biomarkers such as LDL cholesterol have been invaluable in the prevention, treatment and identification of at-risk individuals. We propose an integrated genomic-proteomic (biomarker) approach to identify novel causal mediators of CMDs, and illustrate with examples from coronary artery disease, stroke, chronic kidney disease and lipids. Our approach is based on Mendelian Randomization (MR), a statistical genetics method that uses genetic associations with both the putative causal factor (i.e. exposure) and the cardiovascular outcome to infer causality. MR protects against confounding and reverse causation. We also discuss novel biomarkers such as epigenetic signatures and polygenic risk scores. Multi-omics holds the promise of better risk stratification, identification of new disease pathways, and paves the way for novel therapeutic interventions. 

About Guillaume Paré
Dr. 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, 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 Dr. Thomas Hudson. He further trained in genetic epidemiology with Dr. 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 high-throughput biomarker screens with genetics, bioinformatics and epidemiology to identify novel cardio-metabolic biomarkers. He has published over 340 original contributions in peer-reviewed journals. These include first or last authored articles in the NEJM, Lancet, Circulation, EHJ, Stroke, JACC, Nature Communications, Circulations Genomics and Precision Medicine and AJHG. His papers have been cited over 53,000 times with a corresponding h-index of 97. He was inducted to the Royal Society of Canada’s College of New Scholars, Artist and Scientists in 2018.
 

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