School of Medicine Publications and Presentations

Document Type

Article

Publication Date

4-2016

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.

Comments

Copyright © 2015, Macmillan Publishers Limited

https://rdcu.be/cYp9G

Publication Title

Int J Obes

DOI

10.1038/ijo.2015.217

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics

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