Genetics & Genomics

June 16, 2022

BMI genetics influence heart function

Vanderbilt researchers have discovered that a genetic predisposition to elevated body mass index increases the risk of diastolic dysfunction — a cardiac condition that can lead to heart failure.

Diastolic dysfunction occurs in a “stiff” heart filling at higher pressures. Early diastolic dysfunction (G1DD) increases future risk of heart failure, a condition with no life-extending treatments. 

Nataraja Sarma Vaitinadin, MBBS, PhD, MPH, and colleagues sought to identify genetic drivers of G1DD to inform prevention and treatment strategies. Using BioVU, Vanderbilt’s DNA biobank linked to de-identified electronic health records, they identified patients who had undergone echocardiography imaging as part of routine clinical care. 

Among 668 patients with G1DD and 1,772 controls with normal diastolic function, they used polygenic risk scoring and instrumental variable methods to show that body mass index (BMI) genetics significantly associated with increased G1DD risk and that this effect may be mediated through altered glucose metabolism. 

The findings, reported in the Journal of the American Heart Association, suggest that strategies to reduce BMI and control blood glucose might help prevent G1DD and reduce future heart failure risk.

Jonathan Mosley, MD, PhD, is the corresponding senior author of the JAHA study. Other authors include Mingjian Shi, MD, PhD, Christian Shaffer, Eric Farber-Eger, Brandon Lowery, Vineet Agrawal, MD, PhD, Deepak Gupta, MD, MSCI, Dan Roden, MD, and Quinn Wells, MD, PharmD, MSCI. The research was supported by the American Heart Association and National Institutes of Health (grant HL142856). BioVU funding sources are listed here.