Four pleiotropic loci associated with fat mass and lean mass.

Background: 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.
Methods: 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).
Results: 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.
Conclusions: 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.