Work

FRMD6 is associated with peripheral fat distribution in Qinghai Tibetans

Year: 2026

Type: article

Abstract: Objective Tibetan highlanders have adapted to chronic hypoxia, but the genetic basis of their body composition is poorly understood. We conducted the first genome-wide association study of body composition in a Qinghai Tibetan highland migrant population to identify genetic variants associated with regional adiposity. Methods We analyzed 33 body composition phenotypes in 1,231 Qinghai Tibetan individuals genotyped on an Asian-Screening Array (~ 750,000 SNPs). Outliers beyond ± 3 SD were excluded, and phenotypes were adjusted for age and sex. Genome-wide association analyses were performed using a linear mixed model (GEMMA) to account for relatedness and population stratification. Results The lead variant rs11626565, located upstream of FRMD6 , showed genome-wide significant associations with multiple fat traits. The strongest signals were for limb and gynoid fat percentages, including right leg ( P = 3.56 × 10 − 12 ), gynoid ( P = 2.37 × 10 − 11 ), left leg ( P = 3.50 × 10 − 11 ), left arm ( P = 1.68 × 10 − 10 ), and right arm ( P = 1.50 × 10 − 9 ). Effect sizes were substantially larger for these regional fat measures than for total body fat percentage ( P = 8.44 × 10 − 8 ). Suggestive associations ( P < 1.0 × 10 − 5 ) were also identified for height ( TMC2 ), BMI and weight ( SFXN1, ADCY2 ), waist and hip circumference ( NTM, WAPL-LDB3 ), fat-free and skeletal muscle mass ( DLGAP2 ), and android and visceral fat measures ( ETS1 ). Conclusions This first GWAS of body composition in a Tibetan population identifies FRMD6 as a novel locus with exceptionally strong and specific effects on limb and gynoid fat distribution, highlighting its potential role in regional subcutaneous adipose tissue distribution.

Source: Human Genomics

DOI: 10.1186/s40246-026-01063-1