Researchers at Washington University School of Medicine in St. Louis have received a four-year grant of $ 8.8 million to advance research aimed at finding out how a person’s risk for cardiometabolic disorders such as heart disease and type -2 Diabetes is influenced by the interaction of certain genes with demographic and lifestyle factors.
Beyond the small percentage of disease risk explained by genes alone, this study will examine how a person’s gender, race, ethnicity, smoking, alcohol consumption, diet, and physical activity level can combine with genetic risks to trigger the metabolic processes that underlie heart disease.
By examining genomic and lifestyle factors that contribute to cardiometabolic health through their interactions between sexes and diverse populations, our research can help advance the emerging field of precision medicine. ”
DC Rao, PhD, study director, professor of biostatistics, genetics, psychiatry and mathematics
Rao’s key co-researchers at the School of Medicine include cardiologist Lisa de las Fuentes, MD, professor of medicine and biostatistics, and statistical geneticist C. Charles Gu, PhD, associate professor of biostatistics and genetics.
Precision medicine uses information about a person’s genetic makeup, metabolism, and other biological and lifestyle factors to optimize strategies that may prevent or treat a health condition. Such personalized treatment approaches are more likely to be successful for individual patients than a uniform approach.
Funded by the National Institutes of Health (NIH), this new research is the third in a series of similar studies in which Rao and his team 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 associated with African ancestors, but the study lacked the sample size required to robustly validate the interactions as statistically significant.
The current study, involving researchers inside and outside the United States, will overcome this hurdle by expanding the sample size ten times to include data from more than 1 million people, including people from several countries outside the United States. With a sample of 912,000 European, 231,000 Asian, 91,000 African, and 33,000 Hispanic people, this will be the largest and most diverse study of gene-lifestyle interactions.
With a strong focus on gene-lifestyle interactions, Rao’s study marks a departure from traditional genome-wide association studies (GWAS), which quickly scan the genomes of many people to find genetic variations associated with a particular disease. His approach, known as a genome-wide interaction study (GWIS), has the potential to show how smoking, alcohol use, 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 increase risk a heart attack or stroke.
“The study aims to identify new gene-lifestyle interactions that contribute to cardiometabolic disease risk and to better understand the molecular mechanisms underlying these interactions,” said Gu. “By describing associated molecular biomarkers and traits such as DNA methylation, gene expression and metabolites in detail, the study could reveal new possibilities for treating diseases.”
de las Fuentes added: “Our results could uncover new diagnostic and therapeutic tools, identify targets for novel drug development and serve as the basis for a more precise, personalized approach to health care for heart disease, diabetes and other metabolic diseases. Project has great potential, to advance the field. “
Washington University Medical School