In:
PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 1 ( 2023-1-6), p. e0279932-
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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0279932
DOI:
10.1371/journal.pone.0279932.g001
DOI:
10.1371/journal.pone.0279932.g002
DOI:
10.1371/journal.pone.0279932.t001
DOI:
10.1371/journal.pone.0279932.t002
DOI:
10.1371/journal.pone.0279932.t003
DOI:
10.1371/journal.pone.0279932.t004
DOI:
10.1371/journal.pone.0279932.t005
DOI:
10.1371/journal.pone.0279932.s001
DOI:
10.1371/journal.pone.0279932.s002
DOI:
10.1371/journal.pone.0279932.s003
DOI:
10.1371/journal.pone.0279932.s004
DOI:
10.1371/journal.pone.0279932.s005
DOI:
10.1371/journal.pone.0279932.s006
DOI:
10.1371/journal.pone.0279932.s007
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2267670-3
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