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

Abstract

BackgroundTo 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 MethodsSex-combined and sex-stratified analyses were performed on each trait with (TRAIT-BMI) or without (TRAIT) adjustment for BMI, and cohort-specific results were combined via a fixed effects meta-analysis. A total of 2,513 subjects of European descent were available for the discovery phase. For replication, 2,171 European Americans and 772 African Americans were available.ResultsA total of 52 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.ConclusionsOur 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.

Genetic Basis for Sex Differences in Obesity and Lipid Metabolism

“…The 14 loci collectively explained 1.34% of the waist-to-hip ratio variance in women and 0.46% of the variance in men. Subsequent studies confirmed these loci in genome-wide associations with subcutaneous and visceral adipose tissue measured by CT scan (37, 104). When sex-stratified studies were performed, the reported loci had statistically significant associations with fat distribution in women, but not in men.…”

Genomic associations with bill length and disease reveal drift and selection across island bird populations

“…; MAP3K14 , Thu and Richmond ), or with potential to enable adaptation to climate (e.g., DLAT , Blier and Guderley ; SNX29 , Sung et al. ). These findings are reflected in other studies that utilize genome scans to detect signatures of selection.…”

Sex Hormones and Sex Chromosomes Cause Sex Differences in the Development of Cardiovascular Diseases

“…These include loci on the autosomes as well as on the X chromosome. 35, 36 In the mouse, numerous genetic loci with differential effects in males and females have been described, including several loci on chromosome X. 30, 37 The mechanisms underlying sex-specific effects of genetic polymorphisms on obesity merit further study.…”