BMI Bests Polygenic Risk Scores for Predicting Obesity Later in Life

New research from the Michigan Medicine Frankel Cardiovascular Center and the Massachusetts General Hospital Cardiovascular Research Center suggests a patient’s BMI measurements could serve as a better predictor for future obesity than a polygenic risk score(PRS).

An analysis of data from more than 2500 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study indicated BMI in young adulthood explained more than 50% of the variation in BMI 25 years later in midlife compared to just 13.6% when using PRS.

"There's been a lot of attention to the idea of using genetic information to understand your risk of obesity or being overweight, and for potential drug development to address those genetic risks," said lead investigator Venkatesh Murthy, MD, PhD, associate professor of internal medicine and radiology at the University of Michigan. "We wanted to understand how, if at all, genetic data would add to the information already routinely available in clinic. It turns out, our standard clinical exam, including an assessment of BMI, actually has vastly more information to help guide patient care."

In an effort to assess the value of polygenic risk, cardiorespiratory fitness, familial history of overweight, and BMI in young adulthood in predicting a patient’s BMI over time, investigators conducted a prospective cohort study of 1608 white individuals and 909 black individuals from the CARDIA study. All participants included in the analysis were between the ages of 18 and 30 and recruited from 1 of 4 field centers in Minnesota, California, Illinois, or Alabama between 1985 and 1986.

As part of the CARDIA study, all patients included in the analysis had 25-year follow-up information available and BMI at this visit was used and the primary outcome measure of the current analysis. Investigators pointed out analysis of data occurred between April 2019 and September 29, 2019.

Upon analysis, a gradual increase in BMI was noted during the follow-up period—among white individuals, this translated to BMI increases in approximately 5 white and 7 black individuals. Investigators pointed out age, sex, and self-reported parental history of overweight explained between 5.1% (year 25) and 6.9% (year 0) of the variance in BMI among white individuals and between 6.9% (year 10) and 10.3% (year 0) of variance in BMI among black individuals.

When including PRS and 10 principals opponents of ancestry, the variance increased explained between 11.9% (year 0) and 13.8% (year 20; P<0.001 for both). When adding fitness, the variance explained increased to between 18.1% (year 25) and 24.0% (year 0; P<0.001 for both).

Results of the investigators’ analyses revealed baseline BMI in young adulthood was the strongest factor, explaining 74.6% of the variation in BMI at 5 years and 52.3% of the variation in BMI in midlife when combined with age, sex, and self-reported parental history of overweight. These figures represent a 5.6-fold increase compared to PRS at 5 years and a 3.8-fold increase at midlife.

In fully-adjusted analyses, investigators noted the observed effect sizes for fitness and PRS on BMI were comparable in opposite directions. Investigators also pointed out the additional explanatory capacity of the PRS among black individuals included in the study was lower than that observed among white individuals.

Additionally, baseline BMI and surveillance of BMI over time was associated with increased predictability of BMI at 25 years (mean error in predicted BMI 0 kg/m2 (95% CI, −11.4 to 11.4) to 0 kg/m2 (95% CI, −8.5 to 8.5) for baseline BMI and mean error 0 kg/m2 (95% CI, −5.3 to 5.3) for BMI surveillance).

"Ultimately, while genetic risk may be most important in those individuals with rare inherited causes of obesity, for the majority of the population at risk for becoming obese, universal recommendations like healthy eating and remaining active are important and should be reviewed regularly with your personal physician,” said study investigator Ravi Shah, MD, assistant professor of medicine at Harvard Medical School and member of heart failure/transplant section at Massachusetts General Hospital.

This study, titled “Polygenic Risk, Fitness, and Obesity in the Coronary Artery Risk Development in Young Adults (CARDIA) Study,” is published in JAMA Cardiology.