Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
Year: 2020
Type: article
Abstract: Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body-mass-index (up to 77,167 participants), following up 16 loci in an additional 29 studies (up to 113,636 subjects). We identified 13 novel loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1, and CPEB4 (P 1.9 × 10−9 to 1.8 × 10−40), and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex-difference 1.9 × 10−3 to 1.2 × 10−13). These findings provide evidence for multiple loci that modulate body fat distribution, independent of overall adiposity, and reveal powerful gene-by-sex interactions.
Source: UNC Libraries
DOI: 10.17615/2jpr-nz21
Authors: Holmes, Christopher C, Speliotes, Elizabeth K, Mägi, Reedik, Esko, Tõnu, Bouatia-Naji, Nabila, Randall, Joshua C, Weedon, Michael N, Kilpeläinen, Tuomas O, Monda, Keri L, Heid, Iris M, Moffatt, Miriam F, Winkler, Thomas W, Zillikens, M Carola, Kaplan, Lee M, Molony, Cliona, Thorleifsson, Gudmar, Min, Josine L, Luan, Jian'an, Kutalik, Zoltán, Liang, Liming, Dixon, Anna L, Ingelsson, Erik, Li, Shengxu, White, Charles C, Vedantam, Sailaja, Willer, Cristen J, Jackson, Anne U, Steinthorsdottir, Valgerdur, Workalemahu, Tsegaselassie, Qi, Lu, Berndt, Sonja I, Harris, Tamara B
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4297970379