Journal
INTERNATIONAL JOURNAL OF OBESITY
Volume 40, Issue 4, Pages 662-674Publisher
SPRINGERNATURE
DOI: 10.1038/ijo.2015.217
Keywords
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Categories
Funding
- Medical Research Council of Canada
- Canadian Institute for Health Research [FRCN-CCT-83028]
- National Heart, Lung, and Blood Institute (NHLBI) [HL-45670, HL-47323, HL-47317, HL-47327, HL-47321, R01-HL-098445]
- COBRE center grant [8P20 GM-1033528]
- Nutrition Obesity Research Center grant from the National Institutes of Health [NIH 2P30DK072476]
- National Institute of General Medical Sciences of the National Institutes of Health [1 U54 GM104940]
- University of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C]
- Northwestern University [HHSN268201300027C]
- University of Minnesota [HHSN268201300028C]
- Kaiser Foundation Research Institute [HHSN268201300029C]
- Johns Hopkins University School of Medicine [HHSN268200900041C]
- Intramural Research Program of the National Institute on Aging (NIA) [AG0005]
- NHLBI [R01-HL-098445]
- John W. Barton Sr. Chair in Genetics and Nutrition
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BACKGROUND: To identify loci associated with abdominal fat and replicate prior findings, we performed genome-wide association (GWA) studies of abdominal fat traits: subcutaneous adipose tissue (SAT); visceral adipose tissue (VAT); total adipose tissue (TAT) and visceral to subcutaneous adipose tissue ratio (VSR). SUBJECTS AND METHODS: Sex-combined and sex-stratified analyses were performed on each trait with (TRAIT-BMI) or without (TRAIT) adjustment for body mass index (BMI), and cohort-specific results were combined via a fixed effects meta-analysis. A total of 2513 subjects of European descent were available for the discovery phase. For replication, 2171 European Americans and 772 African Americans were available. RESULTS: A total of 52 single-nucleotide polymorphisms (SNPs) encompassing 7 loci showed suggestive evidence of association (P < 1.0 x 10(-6)) with abdominal fat in the sex-combined analyses. The strongest evidence was found on chromosome 7p14.3 between a SNP near BBS9 gene and VAT (rs12374818; P = 1.10 x 10(-7)), an association that was replicated (P = 0.02). For the BMI-adjusted trait, the strongest evidence of association was found between a SNP near CYCSP30 and VAT-BMI (rs10506943; P = 2.42 x 10(-7)). Our sex-specific analyses identified one genome-wide significant (P < 5.0 x 10(-8)) locus for SAT in women with 11 SNPs encompassing the MLLT10, DNAJC1 and EBLN1 genes on chromosome 10p12.31 (P = 3.97 x 10(-8) to 1.13 x 10(-8)). The THNSL2 gene previously associated with VAT in women was also replicated (P = 0.006). The six gene/loci showing the strongest evidence of association with VAT or VAT-BMI were interrogated for their functional links with obesity and inflammation using the Biograph knowledge-mining software. Genes showing the closest functional links with obesity and inflammation were ADCY8 and KCNK9, respectively. CONCLUSIONS: Our results provide evidence for new loci influencing abdominal visceral (BBS9, ADCY8, KCNK9) and subcutaneous (MLLT10/DNAJC1/EBLN1) fat, and confirmed a locus (THNSL2) previously reported to be associated with abdominal fat in women.
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