Nature Research, Nature Communications, (7), p. 13357
Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways. ; Kari Stefansson, Valgerdur Steinthorsdottir, Gudmar Thorleifsson and Unnur Thorsteinsdottir are used by deCODE Genetics/Amgen inc. Gerard Waeber and Peter Vollenweider received an unrestricted grant from GSK to build the CoLaus study. Bruce M. Psaty serves on a DSMB for a clinical trial of a device funded by the manufacturer (Zoll LifeCor).