Genome-Wide Association for Abdominal Subcutaneous and Visceral Adipose Reveals a Novel Locus for Visceral Fat in Women

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 o...

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Main Authors:	Fox, Caroline S., Liu, Yongmei, White, Charles C., Feitosa, Mary, Smith, Albert V., Heard-Costa, Nancy, Lohman, Kurt, Johnson, Andrew D., Foster, Meredith C., Greenawalt, Danielle M., Griffin, Paula, Ding, Jinghong, Newman, Anne B., Tylavsky, Fran, Miljkovic, Iva, Kritchevsky, Stephen B., Launer, Lenore, Garcia, Melissa, Eiriksdottir, Gudny, Carr, J. Jeffrey, Gudnason, Vilmunder, Harris, Tamara B., Cupples, L. Adrienne, Borecki, Ingrid B.
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349734/

id	pubmed-3349734
recordtype	oai_dc
spelling	pubmed-33497342012-05-15 Genome-Wide Association for Abdominal Subcutaneous and Visceral Adipose Reveals a Novel Locus for Visceral Fat in Women Fox, Caroline S. Liu, Yongmei White, Charles C. Feitosa, Mary Smith, Albert V. Heard-Costa, Nancy Lohman, Kurt Johnson, Andrew D. Foster, Meredith C. Greenawalt, Danielle M. Griffin, Paula Ding, Jinghong Newman, Anne B. Tylavsky, Fran Miljkovic, Iva Kritchevsky, Stephen B. Launer, Lenore Garcia, Melissa Eiriksdottir, Gudny Carr, J. Jeffrey Gudnason, Vilmunder Harris, Tamara B. Cupples, L. Adrienne Borecki, Ingrid B. Research Article 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. Public Library of Science 2012-05-10 /pmc/articles/PMC3349734/ /pubmed/22589738 http://dx.doi.org/10.1371/journal.pgen.1002695 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Fox, Caroline S. Liu, Yongmei White, Charles C. Feitosa, Mary Smith, Albert V. Heard-Costa, Nancy Lohman, Kurt Johnson, Andrew D. Foster, Meredith C. Greenawalt, Danielle M. Griffin, Paula Ding, Jinghong Newman, Anne B. Tylavsky, Fran Miljkovic, Iva Kritchevsky, Stephen B. Launer, Lenore Garcia, Melissa Eiriksdottir, Gudny Carr, J. Jeffrey Gudnason, Vilmunder Harris, Tamara B. Cupples, L. Adrienne Borecki, Ingrid B.
spellingShingle	Fox, Caroline S. Liu, Yongmei White, Charles C. Feitosa, Mary Smith, Albert V. Heard-Costa, Nancy Lohman, Kurt Johnson, Andrew D. Foster, Meredith C. Greenawalt, Danielle M. Griffin, Paula Ding, Jinghong Newman, Anne B. Tylavsky, Fran Miljkovic, Iva Kritchevsky, Stephen B. Launer, Lenore Garcia, Melissa Eiriksdottir, Gudny Carr, J. Jeffrey Gudnason, Vilmunder Harris, Tamara B. Cupples, L. Adrienne Borecki, Ingrid B. Genome-Wide Association for Abdominal Subcutaneous and Visceral Adipose Reveals a Novel Locus for Visceral Fat in Women
author_facet	Fox, Caroline S. Liu, Yongmei White, Charles C. Feitosa, Mary Smith, Albert V. Heard-Costa, Nancy Lohman, Kurt Johnson, Andrew D. Foster, Meredith C. Greenawalt, Danielle M. Griffin, Paula Ding, Jinghong Newman, Anne B. Tylavsky, Fran Miljkovic, Iva Kritchevsky, Stephen B. Launer, Lenore Garcia, Melissa Eiriksdottir, Gudny Carr, J. Jeffrey Gudnason, Vilmunder Harris, Tamara B. Cupples, L. Adrienne Borecki, Ingrid B.
author_sort	Fox, Caroline S.
title	Genome-Wide Association for Abdominal Subcutaneous and Visceral Adipose Reveals a Novel Locus for Visceral Fat in Women
title_short	Genome-Wide Association for Abdominal Subcutaneous and Visceral Adipose Reveals a Novel Locus for Visceral Fat in Women
title_full	Genome-Wide Association for Abdominal Subcutaneous and Visceral Adipose Reveals a Novel Locus for Visceral Fat in Women
title_fullStr	Genome-Wide Association for Abdominal Subcutaneous and Visceral Adipose Reveals a Novel Locus for Visceral Fat in Women
title_full_unstemmed	Genome-Wide Association for Abdominal Subcutaneous and Visceral Adipose Reveals a Novel Locus for Visceral Fat in Women
title_sort	genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women
description	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.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349734/
_version_	1611528817135845376

Genome-Wide Association for Abdominal Subcutaneous and Visceral Adipose Reveals a Novel Locus for Visceral Fat in Women

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