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Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women

Fox, C.S., Liu, Y., White, C.C., Feitosa, M., Smith, A.V., Heard-Costa, N., Lohman, K., Johnson, A.D., Foster, M.C., Greenawalt, D.M., Griffin, P., Ding, J., Newman, A.B., Tylavsky, F., Milijkovic, I., Kritchevsky, S.B., Launer, L., Garcia, M., Eriksdottir, G., Carr, J.J., Gudnason, V., Harris, T.B., Cupples, L.A., Borecki, I.B., Cooper, C., Aihie-Sayer, A. and Syddall, H.E. (2012) Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women PLoS Genetics, 8, e1002695. (doi:10.1371/journal.pgen.1002695). (PMID:22589738).

Record type: Article

Abstract

Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT) to uncover novel loci for body fat distribution among participants of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously) in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio, our most significant p-value was rs11118316 at LYPLAL1 gene (p = 3.1×10E-09), previously identified in association with waist–hip ratio. For SAT, the most significant SNP was in the FTO gene (p = 5.9×10E-08). Given the known gender differences in body fat distribution, we performed sex-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6×10-08), but not men (p = 0.75). Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006) but not men (p = 0.24) for BMI and waist circumference (p = 0.04 [women], p = 0.49 [men]). Finally, we interrogated our data for the 14 recently published loci for body fat distribution (measured by waist–hip ratio adjusted for BMI); associations were observed at 7 of these loci. In contrast, we observed associations at only 7/32 loci previously identified in association with BMI; the majority of overlap was observed with SAT. Genome-wide association for visceral and subcutaneous fat revealed a SNP for VAT in women. More refined phenotypes for body composition and fat distribution can detect new loci not previously uncovered in large-scale GWAS of anthropometric traits.

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Published date: 10 May 2012
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 343068
URI: http://eprints.soton.ac.uk/id/eprint/343068
ISSN: 1553-7390
PURE UUID: 54c5efbc-41b3-4ec4-a32b-a1cb1606fc12
ORCID for C. Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for H.E. Syddall: ORCID iD orcid.org/0000-0003-0171-0306

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Date deposited: 24 Sep 2012 10:52
Last modified: 18 Jul 2017 05:24

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Contributors

Author: C.S. Fox
Author: Y. Liu
Author: C.C. White
Author: M. Feitosa
Author: A.V. Smith
Author: N. Heard-Costa
Author: K. Lohman
Author: A.D. Johnson
Author: M.C. Foster
Author: D.M. Greenawalt
Author: P. Griffin
Author: J. Ding
Author: A.B. Newman
Author: F. Tylavsky
Author: I. Milijkovic
Author: S.B. Kritchevsky
Author: L. Launer
Author: M. Garcia
Author: G. Eriksdottir
Author: J.J. Carr
Author: V. Gudnason
Author: T.B. Harris
Author: L.A. Cupples
Author: I.B. Borecki
Author: C. Cooper ORCID iD
Author: A. Aihie-Sayer
Author: H.E. Syddall ORCID iD

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