Assessing how genes and more impact cardiometabolic disease risk

Aug. 12, 2021

Researchers at Washington University School of Medicine in St. Louis have received a four-year, $8.8 million grant to ramp up research aimed at unraveling how an individual’s risks for cardiometabolic diseases, such as heart disease and Type 2 diabetes, are influenced by the interaction of specific genes with demographic and lifestyle factors.

Going beyond the small percentage of disease risk explained by genes alone, this study will explore how an individual’s gender, race, ethnicity, smoking, alcohol use, diet and exercise levels may combine with genetic risks to trigger the metabolic processes that underlie heart disease.

Precision medicine uses information about a person’s genetic makeup, metabolism and other biological and lifestyle factors to optimize strategies that potentially can prevent or treat a health condition. Such personalized approaches to treatment are more likely to be successful for individual patients, rather than a one-size-fits-all approach.

Funded by the National Institutes of Health (NIH), this new investigation will be the third in a series of similar studies in which researchers use statistical analysis to identify gene-lifestyle interactions associated with cardiovascular and cardiometabolic diseases — the leading causes of death in the United States and worldwide.

Their original study identified promising gene-lifestyle interactions, including several tied to African ancestry, but the study lacked the sample size necessary to robustly validate the interactions as statistically significant.

The current study, involving investigators from within and outside the U.S., will overcome that hurdle by expanding the sample size tenfold to include data from more than 1 million individuals, including people from several countries outside the United States. With a sample of 912,000 people of European ancestry, 231,000 of Asian ancestry, 91,000 of African ancestry and 33,000 of Hispanic ancestry, it will be the largest, most diverse investigation of gene-lifestyle interactions attempted, the university contends.

By focusing heavily on gene-lifestyle interactions, the study represents a shift from traditional genomewide association studies (GWAS), which rapidly scan the genomes of many people to find genetic variations associated with a particular disease. His approach, known as a genomewide interaction study (GWIS), adds the potential to show how smoking, alcohol consumption, physical activity, obesity, sleep duration and other lifestyle factors interact with genes to influence high blood pressure, diabetes, cholesterol levels and other metabolic traits that may increase the risk of a heart attack or stroke.

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