Four pleiotropic loci associated with fat mass and lean mass.

Abstract

Fat mass and lean mass are two biggest components of body mass. Both fat mass and lean mass are under strong genetic determinants and are correlated. We performed a bivariate genome-wide association meta-analysis of (lean adjusted) leg fat mass and (fat adjusted) leg lean mass in 12,517 subjects from 6 samples, and followed by in silico replication in large-scale UK biobank cohort sample (N = 370 097). We identified four loci that were significant at the genome-wide significance (GWS, α = 5.0 × 10^-8) level at the discovery meta-analysis, and successfully replicated in the replication sample: 2q36.3 (rs1024137, p_discovery = 3.32 × 10^-8, p_replication = 4.07 × 10^-13), 5q13.1 (rs4976033, p_discovery = 1.93 × 10^-9, p_replication = 6.35 × 10^-7), 12q24.31 (rs4765528, p_discovery = 7.19 × 10^-12, p_replication = 1.88 × 10^-11) and 18q21.32 (rs371326986, p_discovery = 9.04 × 10^-9, p_replication = 2.35 × 10^-95). The above four pleiotropic loci may play a pleiotropic role for fat mass and lean mass development. Our findings further enhance the understanding of the genetic association between fat mass and lean mass and provide a new theoretical basis for their understanding.