Genetic predisposition to obesity widens and skews the BMI distribution

Abstract

Genetic studies of BMI have largely focused on how average BMI changes with SNPs or polygenic risk scores (PRS). We examine the effects of a BMI PRS on changes in BMI percentiles, range, and skewness using quantile regression and US nationally representative data from the Health and Retirement Survey. We find that the BMI PRS is associated with meaningfully larger weight increases at higher than lower BMI percentiles; the 90th BMI percentile increases by 4.7 units with a one SD increase in the PRS compared to 1.5 units at the 10th percentile (both effects individually significant and significantly different from each other p ≤ 0.0001). Our results suggest that PRS effects at average BMI mask substantial heterogeneity for individuals ranking at different BMI percentiles and that genetic effects are associated with greater spread and right skewness of the BMI distribution.