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

Fox, CS and Liu, Y and White, CC and Feitosa, M and Smith, AV and Heard-Costa, N and Lohman, K and Johnson, AD and Foster, MC and Greenawalt, DM and Griffin, P and Ding, J and Newman, AB and Tylavsky, F and Miljkovic, I and Kritchevsky, SB and Launer, L and Garcia, M and Eiriksdottir, G and Carr, JJ and Gudnason, V and Harris, TB and Cupples, LA and Borecki, IB (2012) Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. PLoS Genetics, 8 (5). ISSN 1553-7390

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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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Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
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, ABANEWMAN@pitt.eduANEWMAN
Tylavsky, F
Miljkovic, IMiljkovicI@edc.pitt.eduIVM1
Kritchevsky, SB
Launer, L
Garcia, M
Eiriksdottir, G
Carr, JJ
Gudnason, V
Harris, TB
Cupples, LA
Borecki, IB
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
InvestigatorDupuis, JoséeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorLangenberg, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorProkopenko, IngaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorSaxena, RichaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorSoranzo, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorJackson, Anne UUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorWheeler, EleanorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorGlazer, Nicole LUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorBouatia-Naji, NabilaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorGloyn, Anna LUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorLindgren, Cecilia MUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorMägi, ReedikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorMorris, Andrew PUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorRandall, JoshuaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorJohnson, TobyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorElliott, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorRybin, DenisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorThorleifsson, GudmarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorSteinthorsdottir, ValgerdurUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorHenneman, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorGrallert, HaraldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorDehghan, AbbasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorHottenga, Jouke JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorFranklin, Christopher SUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorNavarro, PauUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorSong, KijoungUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorGoel, AnujUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorPerry, John R BUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorEgan, Josephine MUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorLajunen, TainaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorGrarup, NielsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorSparsø, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorDoney, AlexUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorVoight, Benjamin FUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorStringham, Heather MUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorLi, ManUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorKanoni, StavroulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorShrader, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorCavalcanti-Proença, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorKumari, MeenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorQi, LuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorTimpson, Nicholas JUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorGieger, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorZabena, CarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorRocheleau, GhislainUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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InvestigatorAn, PingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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InvestigatorCornelis, MarilynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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InvestigatorDay, Ian N MUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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InvestigatorHingorani, Aroon DUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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InvestigatorJohnson, Paul R VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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InvestigatorJula, AnttiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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InvestigatorMangino, MassimoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorManning, Alisa KUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorMartínez-Larrad, María TeresaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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InvestigatorPotter, Simon CUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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InvestigatorSingleton, AndrewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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InvestigatorScuteri, AngeloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorSchlessinger, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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InvestigatorRuokonen, AimoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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InvestigatorWaterworth, Dawn MUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorVollenweider, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorPeltonen, LeenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorMooser, VincentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorAbecasis, R GoncaloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorWareham, Nicholas JUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorSladek, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorFroguel, PhilippeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorWatanabe, Richard MUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorMeigs, James BUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorGroop, LeifUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorBoehnke, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorMcCarthy, Mark IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorFlorez, Jose CUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
InvestigatorBarroso, InêsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
EditorBray, MollyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 May 2012
Date Type: Publication
Journal or Publication Title: PLoS Genetics
Volume: 8
Number: 5
DOI or Unique Handle: 10.1371/journal.pgen.1002695
Schools and Programs: School of Public Health > Epidemiology
Refereed: Yes
ISSN: 1553-7390
MeSH Headings: Adult; Aged; Body Mass Index; Cytokines--genetics; European Continental Ancestry Group; Female; Genome-Wide Association Study; HapMap Project; Humans; Intra-Abdominal Fat; Lysophospholipase--genetics; Male; Middle Aged; Phenotype; Polymorphism, Single Nucleotide; Proteins--genetics; Sex Characteristics; Subcutaneous Fat, Abdominal
Other ID: NLM PMC3349734
PubMed Central ID: PMC3349734
PubMed ID: 22589738
Date Deposited: 04 Oct 2012 14:12
Last Modified: 22 May 2019 12:55
URI: http://d-scholarship.pitt.edu/id/eprint/15565

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