Evolutionary analyses of gene by environment variants associated to body shape in human populations

Abstract

Obesity and body fat distribution is a complex phenotype highly heritable. Genetic variants showing association with BMI, a measure of body size, or waist-to-hip ratio adjusted for BMI (WHRadjBMI ), a measure of body shape, have been identified through genome-wide association studies. It is well known that body size and shape change as people grow older and in addition there are substantial changes in both size and shape between men and women. These changes have been explained by means of several evolutionary hypotheses. However little is known about the evolution of the genetic variants underlying these phenotypes. In this study we have tested from the evolutionary perspective 12 SNPs associated with BMI with age-specific effects and 49 SNPs associated with WHRadjBMI with sex-specific effects identified and described by Winkler and Shungin. For that, we have analysed the genetic variation of those loci in human population and tested the presence of differential patterns of selective pressures in 940 unrelated individuals from 53 populations from the Human Genome Diversity Panel in a collaboration with Centre Etude Polymorphism Human (HGDP-CEPH). By applying different statistical methods, we detect gender associated selective pressures on genetic scores for WHRadjBMI differentially acting over populations , as well as limit evidence for age and BMI.