Large-scale exome sequence analysis identifies sex- and age-specific determinants of obesity.

ABSTRACT: Obesity contributes substantially to the global burden of disease and has a significant heritable component. Recent large-scale exome sequencing studies identified several genes in which rare, protein-coding variants have large effects on adult body mass index (BMI). Here we extended such work by performing sex-stratified associations in the UK Biobank study (N∼420,000). We identified genes in which rare heterozygous loss-of-function increases adult BMI in women (DIDO1, PTPRG, and SLC12A5) and in men (SLTM), with effect sizes up to ∼8 kg/m². This is complemented by analyses implicating rare variants in OBSCN and MADD for recalled childhood adiposity. The known functions of these genes, as well as findings of common variant genome-wide pathway e

SUBMITTER: Kaisinger LR 

PROVIDER: S-EPMC10435378 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature