Systems genetics analysis of human body fat distribution genes identifies adipocyte processes.

ABSTRACT: Excess abdominal fat is a sexually dimorphic risk factor for cardio-metabolic disease and is approximated by the waist-to-hip ratio adjusted for body mass index (WHR_adjBMI). Whereas this trait is highly heritable, few causal genes are known. We aimed to identify novel drivers of WHR_adjBMI using systems genetics. We used two independent cohorts of adipose tissue gene expression and constructed sex- and depot-specific Bayesian networks to model gene-gene interactions from 8,492 genes. Using key driver analysis, we identified genes that, in silico and putatively in vitro, regulate many others. 51-119 key drivers in each network were replicated in both cohorts. In other cell types, 23 of these genes are found in crucial adipocyte pathways: Wnt signaling or mitochondrial f

SUBMITTER: Reed JN 

PROVIDER: S-EPMC11068934 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature