Missense variants in FRS3 affect body mass index in populations of diverse ancestries.

ABSTRACT: Obesity is associated with adverse effects on health and quality of life. Improved understanding of its underlying pathophysiology is essential for developing counteractive measures. To search for sequence variants with large effects on BMI, we perform a multi-ancestry meta-analysis of 13 genome-wide association studies on BMI, including data derived from 1,534,555 individuals of European ancestry, 339,657 of Asian ancestry, and 130,968 of African ancestry. We identify an intergenic 262,760 base pair deletion at the MC4R locus that associates with 4.11 kg/m² higher BMI per allele, likely through downregulation of MC4R. Moreover, a rare FRS3 missense variant, p.Glu115Lys, only found in individuals from Finland, associates with 1.09 kg/m² lower BMI per allele. We also d

SUBMITTER: Jonsdottir AB 

PROVIDER: S-EPMC11937519 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature