Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat

Y. J. Sung, L. Pérusse, M. A. Sarzynski, M. Fornage, S. Sidney, B. Sternfeld, T. Rice, J. G. Terry, D. R. Jacobs, P. Katzmarzyk, J. E. Curran, J. Jeffrey Carr, J. Blangero, S. Ghosh, J. P. Després, T. Rankinen, D. C. Rao, C. Bouchard

    Research output: Contribution to journalArticlepeer-review

    44 Scopus citations

    Abstract

    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 × 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 × 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 × 10 -7). Our sex-specific analyses identified one genome-wide significant (P<5.0 × 10 -8) locus for SAT in women with 11 SNPs encompassing the MLLT10, DNAJC1 and EBLN1 genes on chromosome 10p12.31 (P=3.97 × 10 -8 to 1.13 × 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.

    Original languageEnglish (US)
    Pages (from-to)662-674
    Number of pages13
    JournalInternational Journal of Obesity
    Volume40
    Issue number4
    DOIs
    StatePublished - Apr 1 2016

    ASJC Scopus subject areas

    • Medicine (miscellaneous)
    • Endocrinology, Diabetes and Metabolism
    • Nutrition and Dietetics

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