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

Caroline S. Fox, Yongmei Liu, Charles C. White, Mary Feitosa, Albert V. Smith, Nancy Heard-Costa, Kurt Lohman, Andrew D. Johnson, Meredith C. Foster, Danielle M. Greenawalt, Paula Griffin, Jinghong Ding, Anne B. Newman, Frances Tylavsky, Iva Miljkovic, Stephen B. Kritchevsky, Lenore Launer, Melissa Garcia, Gudny Eiriksdottir, J. Jeffrey Carr & 4 others Vilmunder Gudnason, Tamara B. Harris, L. Adrienne Cupples, Ingrid B. Borecki

Research output: Contribution to journalArticle

159 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere1002695
JournalPLoS genetics
Volume8
Issue number5
DOIs
StatePublished - May 1 2012

Fingerprint

visceral fat
Intra-Abdominal Fat
Subcutaneous Fat
adipose tissue
fat
Body Fat Distribution
genome
Genome
loci
body fat distribution
Single Nucleotide Polymorphism
Waist-Hip Ratio
Genome-Wide Association Study
waist
subcutaneous fat
hips
HapMap Project
woman
tissue
Adiposity

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Fox, C. S., Liu, Y., White, C. C., Feitosa, M., Smith, A. V., Heard-Costa, N., ... Borecki, I. B. (2012). Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. PLoS genetics, 8(5), [e1002695]. https://doi.org/10.1371/journal.pgen.1002695

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, Frances; 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.

In: PLoS genetics, Vol. 8, No. 5, e1002695, 01.05.2012.

Research output: Contribution to journalArticle

Fox, CS, Liu, Y, White, CC, Feitosa, M, Smith, AV, Heard-Costa, N, Lohman, K, Johnson, AD, Foster, MC, Greenawalt, DM, Griffin, P, Ding, J, Newman, AB, Tylavsky, F, Miljkovic, I, Kritchevsky, SB, Launer, L, Garcia, M, Eiriksdottir, G, Carr, JJ, Gudnason, V, Harris, TB, Cupples, LA & Borecki, IB 2012, 'Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women', PLoS genetics, vol. 8, no. 5, e1002695. https://doi.org/10.1371/journal.pgen.1002695
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, Frances ; 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. In: PLoS genetics. 2012 ; Vol. 8, No. 5.
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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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AU - Fox, Caroline S.

AU - Liu, Yongmei

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AU - Smith, Albert V.

AU - Heard-Costa, Nancy

AU - Lohman, Kurt

AU - Johnson, Andrew D.

AU - Foster, Meredith C.

AU - Greenawalt, Danielle M.

AU - Griffin, Paula

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AU - Newman, Anne B.

AU - Tylavsky, Frances

AU - Miljkovic, Iva

AU - Kritchevsky, Stephen B.

AU - Launer, Lenore

AU - Garcia, Melissa

AU - Eiriksdottir, Gudny

AU - Carr, J. Jeffrey

AU - Gudnason, Vilmunder

AU - Harris, Tamara B.

AU - Cupples, L. Adrienne

AU - Borecki, Ingrid B.

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N2 - 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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