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Genome-wide association study of abdominal MRI-measured visceral fat: The multiethnic cohort adiposity phenotype study

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 t...

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Autores principales: Streicher, Samantha A., Lim, Unhee, Park, S. Lani, Li, Yuqing, Sheng, Xin, Hom, Victor, Xia, Lucy, Pooler, Loreall, Shepherd, John, Loo, Lenora W. M., Ernst, Thomas, Buchthal, Steven, Franke, Adrian A., Tiirikainen, Maarit, Wilkens, Lynne R., Haiman, Christopher A., Stram, Daniel O., Cheng, Iona, Le Marchand, Loïc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821421/
https://www.ncbi.nlm.nih.gov/pubmed/36607984
http://dx.doi.org/10.1371/journal.pone.0279932
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author Streicher, Samantha A.
Lim, Unhee
Park, S. Lani
Li, Yuqing
Sheng, Xin
Hom, Victor
Xia, Lucy
Pooler, Loreall
Shepherd, John
Loo, Lenora W. M.
Ernst, Thomas
Buchthal, Steven
Franke, Adrian A.
Tiirikainen, Maarit
Wilkens, Lynne R.
Haiman, Christopher A.
Stram, Daniel O.
Cheng, Iona
Le Marchand, Loïc
author_facet Streicher, Samantha A.
Lim, Unhee
Park, S. Lani
Li, Yuqing
Sheng, Xin
Hom, Victor
Xia, Lucy
Pooler, Loreall
Shepherd, John
Loo, Lenora W. M.
Ernst, Thomas
Buchthal, Steven
Franke, Adrian A.
Tiirikainen, Maarit
Wilkens, Lynne R.
Haiman, Christopher A.
Stram, Daniel O.
Cheng, Iona
Le Marchand, Loïc
author_sort Streicher, Samantha A.
collection PubMed
description 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.
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spelling pubmed-98214212023-01-07 Genome-wide association study of abdominal MRI-measured visceral fat: The multiethnic cohort adiposity phenotype study Streicher, Samantha A. Lim, Unhee Park, S. Lani Li, Yuqing Sheng, Xin Hom, Victor Xia, Lucy Pooler, Loreall Shepherd, John Loo, Lenora W. M. Ernst, Thomas Buchthal, Steven Franke, Adrian A. Tiirikainen, Maarit Wilkens, Lynne R. Haiman, Christopher A. Stram, Daniel O. Cheng, Iona Le Marchand, Loïc PLoS One Research Article 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. Public Library of Science 2023-01-06 /pmc/articles/PMC9821421/ /pubmed/36607984 http://dx.doi.org/10.1371/journal.pone.0279932 Text en © 2023 Streicher et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Streicher, Samantha A.
Lim, Unhee
Park, S. Lani
Li, Yuqing
Sheng, Xin
Hom, Victor
Xia, Lucy
Pooler, Loreall
Shepherd, John
Loo, Lenora W. M.
Ernst, Thomas
Buchthal, Steven
Franke, Adrian A.
Tiirikainen, Maarit
Wilkens, Lynne R.
Haiman, Christopher A.
Stram, Daniel O.
Cheng, Iona
Le Marchand, Loïc
Genome-wide association study of abdominal MRI-measured visceral fat: The multiethnic cohort adiposity phenotype study
title Genome-wide association study of abdominal MRI-measured visceral fat: The multiethnic cohort adiposity phenotype study
title_full Genome-wide association study of abdominal MRI-measured visceral fat: The multiethnic cohort adiposity phenotype study
title_fullStr Genome-wide association study of abdominal MRI-measured visceral fat: The multiethnic cohort adiposity phenotype study
title_full_unstemmed Genome-wide association study of abdominal MRI-measured visceral fat: The multiethnic cohort adiposity phenotype study
title_short Genome-wide association study of abdominal MRI-measured visceral fat: The multiethnic cohort adiposity phenotype study
title_sort genome-wide association study of abdominal mri-measured visceral fat: the multiethnic cohort adiposity phenotype study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821421/
https://www.ncbi.nlm.nih.gov/pubmed/36607984
http://dx.doi.org/10.1371/journal.pone.0279932
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