Discovery genome-wide association study of body composition in 4,386 adults from the UK Biobank’s pilot imaging enhancement study

Livingstone, K. M., Tan, M. H., Abbott, G., Duckham, R. L., Croft, L., Ward, J. , McEvoy, M., Keske, M. A., Austin, C. and Bowe, S. J. (2021) Discovery genome-wide association study of body composition in 4,386 adults from the UK Biobank’s pilot imaging enhancement study. Frontiers in Endocrinology, 12, 692677. (doi: 10.3389/fendo.2021.692677) (PMID:34239500) (PMCID:PMC8259458)

Abstract

Body composition (fat, skeletal muscle and bone mass) is an important determinant of overall health and risk of endocrine disorders such as type 2 diabetes and osteoporosis. Although diet and physical activity are strongly implicated, body composition is also heritable. We conducted a discovery genome-wide association study on 31 phenotypes from the three-compartment body composition model (fat, lean and bone mass) in a set of 4 386 individuals (n = 2 109 males, n = 2 294 females) from the UK Biobank pilot imaging enhancement program that underwent a dual energy X-ray absorptiometry (DXA) scan for assessment of body composition and genetic screening. From 6 137 607 imputed single nucleotide polymorphisms (SNPs) we identified 17 body composition loci (P<5.0 x 10-8). GWAS from the combined dataset identified four statistically significant SNPs (rs7592270, rs145972737, rs13212044, rs77772562). In sex-stratified GWAS, 10 male specific SNPs across all traits were identified and five female specific SNPs. Of the 17 SNPs, six were in or close to a gene where there was a plausible functional connection. Three SNPs (rs7592270, rs77772562 and rs7552312) were correlated with obesity phenotypes, one SNP (rs2236705) with lean phenotypes and two with bone mass phenotypes (rs112098641 and rs113380185). These results highlight candidate genes and biological pathways related to body composition, including glucose metabolism and estrogen regulation, that are of interest to replicate in future studies.

• Item Type: Articles
• Additional Information: KL is supported by a National Health and Medical Research Council Emerging Leadership Investigator Grant (APP1173803). JW is funded by the Lister Prize Fellowship (173096).
• Keywords: Endocrinology, dual energy X-ray absorptiometry, genome-wide association study, loci, bone mass, fat mass, lean mass, body composition, genetics.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ward, Dr Joey
• Authors: Livingstone, K. M., Tan, M. H., Abbott, G., Duckham, R. L., Croft, L., Ward, J., McEvoy, M., Keske, M. A., Austin, C., and Bowe, S. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
• Journal Name: Frontiers in Endocrinology
• Publisher: Frontiers Media
• ISSN: 1664-2392
• ISSN (Online): 1664-2392
• Copyright Holders: Copyright © 2021 Livingstone, Tan, Abbott, Duckham, Croft, Ward, McEvoy, Keske, Austin and Bowe
• First Published: First published in Frontiers in Endocrinology 12: 692677
• Publisher Policy: Reproduced under a Creative Commons License