biostudies-literatureReed JNHHS | NIH | National Institute of Diabetes and Digestive and Kidney DiseasesNIDDK NIH HHSFondation LeducqNHLBI NIH HHSHHS | NIH | National Heart, Lung, and Blood Institutee202402603https://www.ebi.ac.uk/biostudies/studies/S-EPMC11068934biostudies-literatureUnknown7(7)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 fLife science allianceSystems genetics analysis of human body fat distribution genes identifies adipocyte processes.PMC1106893422CVD04T32 HL007284R01 DK118287Ding WLi YMa LCivelek MHuang JReed JNWang TBanka DWabitsch MBjorkegren JLfalseSystems genetics analysis of human body fat distribution genes identifies adipocyte processes.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 f2024-01-01T00:00:00Z2024 Jul2026-06-02T07:01:42.316Z2025-08-14T03:05:51.643ZS-EPMC110689343870207510.26508/lsa.202402603