La Trobe
1175136_Livingstone,K_2021.pdf (2.43 MB)

Discovery Genome-Wide Association Study of Body Composition in 4,386 Adults From the UK Biobank's Pilot Imaging Enhancement Study

Download (2.43 MB)
journal contribution
posted on 2021-08-02, 03:11 authored by Katherine M Livingstone, Mun Hua Tan, Gavin Abbott, Rachel L Duckham, Larry Croft, Joey Ward, Mark McEvoyMark McEvoy, Michelle A Keske, Christopher Austin, Steven J Bowe
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.


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). The funding source had no role in the design or conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.


Publication Date






Article Number

ARTN 692677







Rights Statement

The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.