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Genome-Wide Association of Pericardial Fat Identifies a Unique Locus for Ectopic Fat
Pericardial fat is a localized fat depot associated with coronary artery calcium and myocardial infarction. We hypothesized that genetic loci would be associated with pericardial fat independent of other body fat depots. Pericardial fat was quantified in 5,487 individuals of European ancestry from t...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349742/ https://www.ncbi.nlm.nih.gov/pubmed/22589742 http://dx.doi.org/10.1371/journal.pgen.1002705 |
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author | Fox, Caroline S. White, Charles C. Lohman, Kurt Heard-Costa, Nancy Cohen, Paul Zhang, Yingying Johnson, Andrew D. Emilsson, Valur Liu, Ching-Ti Chen, Y.-D. Ida Taylor, Kent D. Allison, Matthew Budoff, Matthew Rotter, Jerome I. Carr, J. Jeffrey Hoffmann, Udo Ding, Jingzhong Cupples, L. Adrienne Liu, Yongmei |
author_facet | Fox, Caroline S. White, Charles C. Lohman, Kurt Heard-Costa, Nancy Cohen, Paul Zhang, Yingying Johnson, Andrew D. Emilsson, Valur Liu, Ching-Ti Chen, Y.-D. Ida Taylor, Kent D. Allison, Matthew Budoff, Matthew Rotter, Jerome I. Carr, J. Jeffrey Hoffmann, Udo Ding, Jingzhong Cupples, L. Adrienne Liu, Yongmei |
author_sort | Fox, Caroline S. |
collection | PubMed |
description | Pericardial fat is a localized fat depot associated with coronary artery calcium and myocardial infarction. We hypothesized that genetic loci would be associated with pericardial fat independent of other body fat depots. Pericardial fat was quantified in 5,487 individuals of European ancestry from the Framingham Heart Study (FHS) and the Multi-Ethnic Study of Atherosclerosis (MESA). Genotyping was performed using standard arrays and imputed to ∼2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of pericardial fat adjusted for age, sex, weight, and height. A weighted z-score meta-analysis was conducted, and validation was obtained in an additional 3,602 multi-ethnic individuals from the MESA study. We identified a genome-wide significant signal in our primary meta-analysis at rs10198628 near TRIB2 (MAF 0.49, p = 2.7×10(-08)). This SNP was not associated with visceral fat (p = 0.17) or body mass index (p = 0.38), although we observed direction-consistent, nominal significance with visceral fat adjusted for BMI (p = 0.01) in the Framingham Heart Study. Our findings were robust among African ancestry (n = 1,442, p = 0.001), Hispanic (n = 1,399, p = 0.004), and Chinese (n = 761, p = 0.007) participants from the MESA study, with a combined p-value of 5.4E-14. We observed TRIB2 gene expression in the pericardial fat of mice. rs10198628 near TRIB2 is associated with pericardial fat but not measures of generalized or visceral adiposity, reinforcing the concept that there are unique genetic underpinnings to ectopic fat distribution. |
format | Online Article Text |
id | pubmed-3349742 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33497422012-05-15 Genome-Wide Association of Pericardial Fat Identifies a Unique Locus for Ectopic Fat Fox, Caroline S. White, Charles C. Lohman, Kurt Heard-Costa, Nancy Cohen, Paul Zhang, Yingying Johnson, Andrew D. Emilsson, Valur Liu, Ching-Ti Chen, Y.-D. Ida Taylor, Kent D. Allison, Matthew Budoff, Matthew Rotter, Jerome I. Carr, J. Jeffrey Hoffmann, Udo Ding, Jingzhong Cupples, L. Adrienne Liu, Yongmei PLoS Genet Research Article Pericardial fat is a localized fat depot associated with coronary artery calcium and myocardial infarction. We hypothesized that genetic loci would be associated with pericardial fat independent of other body fat depots. Pericardial fat was quantified in 5,487 individuals of European ancestry from the Framingham Heart Study (FHS) and the Multi-Ethnic Study of Atherosclerosis (MESA). Genotyping was performed using standard arrays and imputed to ∼2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of pericardial fat adjusted for age, sex, weight, and height. A weighted z-score meta-analysis was conducted, and validation was obtained in an additional 3,602 multi-ethnic individuals from the MESA study. We identified a genome-wide significant signal in our primary meta-analysis at rs10198628 near TRIB2 (MAF 0.49, p = 2.7×10(-08)). This SNP was not associated with visceral fat (p = 0.17) or body mass index (p = 0.38), although we observed direction-consistent, nominal significance with visceral fat adjusted for BMI (p = 0.01) in the Framingham Heart Study. Our findings were robust among African ancestry (n = 1,442, p = 0.001), Hispanic (n = 1,399, p = 0.004), and Chinese (n = 761, p = 0.007) participants from the MESA study, with a combined p-value of 5.4E-14. We observed TRIB2 gene expression in the pericardial fat of mice. rs10198628 near TRIB2 is associated with pericardial fat but not measures of generalized or visceral adiposity, reinforcing the concept that there are unique genetic underpinnings to ectopic fat distribution. Public Library of Science 2012-05-10 /pmc/articles/PMC3349742/ /pubmed/22589742 http://dx.doi.org/10.1371/journal.pgen.1002705 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Fox, Caroline S. White, Charles C. Lohman, Kurt Heard-Costa, Nancy Cohen, Paul Zhang, Yingying Johnson, Andrew D. Emilsson, Valur Liu, Ching-Ti Chen, Y.-D. Ida Taylor, Kent D. Allison, Matthew Budoff, Matthew Rotter, Jerome I. Carr, J. Jeffrey Hoffmann, Udo Ding, Jingzhong Cupples, L. Adrienne Liu, Yongmei Genome-Wide Association of Pericardial Fat Identifies a Unique Locus for Ectopic Fat |
title | Genome-Wide Association of Pericardial Fat Identifies a Unique Locus for Ectopic Fat |
title_full | Genome-Wide Association of Pericardial Fat Identifies a Unique Locus for Ectopic Fat |
title_fullStr | Genome-Wide Association of Pericardial Fat Identifies a Unique Locus for Ectopic Fat |
title_full_unstemmed | Genome-Wide Association of Pericardial Fat Identifies a Unique Locus for Ectopic Fat |
title_short | Genome-Wide Association of Pericardial Fat Identifies a Unique Locus for Ectopic Fat |
title_sort | genome-wide association of pericardial fat identifies a unique locus for ectopic fat |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349742/ https://www.ncbi.nlm.nih.gov/pubmed/22589742 http://dx.doi.org/10.1371/journal.pgen.1002705 |
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