| Title: | Genome-wide association study of abdominal MRI-measured visceral fat: The multiethnic cohort adiposity phenotype study |
| Journal: | PLOS ONE |
| Published: | 6 Jan 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36607984/ |
| DOI: | https://doi.org/10.1371/journal.pone.0279932 |
| URL: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279932&type=printable |
Publication 10935
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Abstract
Few studies have explored the genetic underpinnings of intra-abdominal visceral fat deposition, which varies substantially by sex and race/ethnicity. Among 1,787 participants in the Multiethnic Cohort (MEC)-Adiposity Phenotype Study (MEC-APS), we conducted a genome-wide association study (GWAS) of the percent visceral adiposity tissue (VAT) area out of the overall abdominal area, averaged across L1-L5 (%VAT), measured by abdominal magnetic resonance imaging (MRI). A genome-wide significant signal was found on chromosome 2q14.3 in the sex-combined GWAS (lead variant rs79837492: Beta per effect allele = -4.76; P = 2.62 × 10-8) and in the male-only GWAS (lead variant rs2968545: (Beta = -6.50; P = 1.09 × 10-9), and one suggestive variant was found at 13q12.11 in the female-only GWAS (rs79926925: Beta = 6.95; P = 8.15 × 10-8). The negatively associated variants were most common in European Americans (T allele of rs79837492; 5%) and African Americans (C allele of rs2968545; 5%) and not observed in Japanese Americans, whereas the positively associated variant was most common in Japanese Americans (C allele of rs79926925, 5%), which was all consistent with the racial/ethnic %VAT differences. In a validation step among UK Biobank participants (N = 23,699 of mainly British and Irish ancestry) with MRI-based VAT volume, both rs79837492 (Beta = -0.026, P = 0.019) and rs2968545 (Beta = -0.028, P = 0.010) were significantly associated in men only (n = 11,524). In the MEC-APS, the association between rs79926925 and plasma sex hormone binding globulin levels reached statistical significance in females, but not in males, with adjustment for total adiposity (Beta = -0.24; P = 0.028), on the log scale. Rs79837492 and rs2968545 are located in intron 5 of CNTNAP5, and rs79926925, in an intergenic region between GJB6 and CRYL1. These novel findings differing by sex and racial/ethnic group warrant replication in additional diverse studies with direct visceral fat measurements.</p>
19 Authors
- Samantha A. Streicher
- Unhee Lim
- S. Lani Park
- Yuqing Li
- Xin Sheng
- Victor Hom
- Lucy Xia
- Loreall Pooler
- John Shepherd
- Lenora W. M. Loo
- Thomas Ernst
- Steven Buchthal
- Adrian A. Franke
- Maarit Tiirikainen
- Lynne R. Wilkens
- Christopher A. Haiman
- Daniel O. Stram
- Iona Cheng
- Loïc Le Marchand
1 Application
| Application ID | Title |
|---|---|
| 16447 | Genetic and non-genetic factor associated with cancer and other chronic diseases across racial/ethnic populations |
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