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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2012
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oai:doaj.org-article:4801b88842b6405eb1c277ac62c33f322021-11-18T06:18:35ZGenome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.1553-73901553-740410.1371/journal.pgen.1002695https://doaj.org/article/4801b88842b6405eb1c277ac62c33f322012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22589738/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Body 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.Caroline S FoxYongmei LiuCharles C WhiteMary FeitosaAlbert V SmithNancy Heard-CostaKurt LohmanGIANT ConsortiumMAGIC ConsortiumGLGC ConsortiumAndrew D JohnsonMeredith C FosterDanielle M GreenawaltPaula GriffinJinghong DingAnne B NewmanFran TylavskyIva MiljkovicStephen B KritchevskyLenore LaunerMelissa GarciaGudny EiriksdottirJ Jeffrey CarrVilmunder GudnasonTamara B HarrisL Adrienne CupplesIngrid B BoreckiPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 8, Iss 5, p e1002695 (2012) |
| institution |
DOAJ |
| collection |
DOAJ |
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| topic |
Genetics QH426-470 |
| spellingShingle |
Genetics QH426-470 Caroline S Fox Yongmei Liu Charles C White Mary Feitosa Albert V Smith Nancy Heard-Costa Kurt Lohman GIANT Consortium MAGIC Consortium GLGC Consortium Andrew D Johnson Meredith C Foster Danielle M Greenawalt Paula Griffin Jinghong Ding Anne B Newman Fran Tylavsky Iva Miljkovic Stephen B Kritchevsky Lenore Launer Melissa Garcia Gudny Eiriksdottir J Jeffrey Carr Vilmunder Gudnason Tamara B Harris L Adrienne Cupples Ingrid B Borecki 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. |
| format |
article |
| author |
Caroline S Fox Yongmei Liu Charles C White Mary Feitosa Albert V Smith Nancy Heard-Costa Kurt Lohman GIANT Consortium MAGIC Consortium GLGC Consortium Andrew D Johnson Meredith C Foster Danielle M Greenawalt Paula Griffin Jinghong Ding Anne B Newman Fran Tylavsky Iva Miljkovic Stephen B Kritchevsky Lenore Launer Melissa Garcia Gudny Eiriksdottir J Jeffrey Carr Vilmunder Gudnason Tamara B Harris L Adrienne Cupples Ingrid B Borecki |
| author_facet |
Caroline S Fox Yongmei Liu Charles C White Mary Feitosa Albert V Smith Nancy Heard-Costa Kurt Lohman GIANT Consortium MAGIC Consortium GLGC Consortium Andrew D Johnson Meredith C Foster Danielle M Greenawalt Paula Griffin Jinghong Ding Anne B Newman Fran Tylavsky Iva Miljkovic Stephen B Kritchevsky Lenore Launer Melissa Garcia Gudny Eiriksdottir J Jeffrey Carr Vilmunder Gudnason Tamara B Harris L Adrienne Cupples Ingrid B Borecki |
| author_sort |
Caroline S Fox |
| 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. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/4801b88842b6405eb1c277ac62c33f32 |
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