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Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs
We performed genome-wide meta-analysis of lipid traits on three samples of Mexican and Mexican American ancestry comprising 4,383 individuals, and followed up significant and highly suggestive associations in three additional Hispanic samples comprising 7,876 individuals. Genome-wide significant sig...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4726092/ https://www.ncbi.nlm.nih.gov/pubmed/26780889 http://dx.doi.org/10.1038/srep19429 |
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author | Below, Jennifer E. Parra, Esteban J. Gamazon, Eric R. Torres, Jason Krithika, S. Candille, Sophie Lu, Yingchang Manichakul, Ani Peralta-Romero, Jesus Duan, Qing Li, Yun Morris, Andrew P. Gottesman, Omri Bottinger, Erwin Wang, Xin-Qun Taylor, Kent D. Ida Chen, Y.-D. Rotter, Jerome I. Rich, Stephen S. Loos, Ruth J. F. Tang, Hua Cox, Nancy J. Cruz, Miguel Hanis, Craig L. Valladares-Salgado, Adan |
author_facet | Below, Jennifer E. Parra, Esteban J. Gamazon, Eric R. Torres, Jason Krithika, S. Candille, Sophie Lu, Yingchang Manichakul, Ani Peralta-Romero, Jesus Duan, Qing Li, Yun Morris, Andrew P. Gottesman, Omri Bottinger, Erwin Wang, Xin-Qun Taylor, Kent D. Ida Chen, Y.-D. Rotter, Jerome I. Rich, Stephen S. Loos, Ruth J. F. Tang, Hua Cox, Nancy J. Cruz, Miguel Hanis, Craig L. Valladares-Salgado, Adan |
author_sort | Below, Jennifer E. |
collection | PubMed |
description | We performed genome-wide meta-analysis of lipid traits on three samples of Mexican and Mexican American ancestry comprising 4,383 individuals, and followed up significant and highly suggestive associations in three additional Hispanic samples comprising 7,876 individuals. Genome-wide significant signals were observed in or near CELSR2, ZNF259/APOA5, KANK2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5, LIPC and CETP for HDL cholesterol, CELSR2, APOB and NCAN/MAU2 for LDL cholesterol, and GCKR, TRIB1, ZNF259/APOA5 and NCAN/MAU2 for triglycerides. Linkage disequilibrium and conditional analyses indicate that signals observed at ABCA1 and LIPC for HDL cholesterol and NCAN/MAU2 for triglycerides are independent of previously reported lead SNP associations. Analyses of lead SNPs from the European Global Lipids Genetics Consortium (GLGC) dataset in our Hispanic samples show remarkable concordance of direction of effects as well as strong correlation in effect sizes. A meta-analysis of the European GLGC and our Hispanic datasets identified five novel regions reaching genome-wide significance: two for total cholesterol (FN1 and SAMM50), two for HDL cholesterol (LOC100996634 and COPB1) and one for LDL cholesterol (LINC00324/CTC1/PFAS). The top meta-analysis signals were found to be enriched for SNPs associated with gene expression in a tissue-specific fashion, suggesting an enrichment of tissue-specific function in lipid-associated loci. |
format | Online Article Text |
id | pubmed-4726092 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47260922016-01-27 Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs Below, Jennifer E. Parra, Esteban J. Gamazon, Eric R. Torres, Jason Krithika, S. Candille, Sophie Lu, Yingchang Manichakul, Ani Peralta-Romero, Jesus Duan, Qing Li, Yun Morris, Andrew P. Gottesman, Omri Bottinger, Erwin Wang, Xin-Qun Taylor, Kent D. Ida Chen, Y.-D. Rotter, Jerome I. Rich, Stephen S. Loos, Ruth J. F. Tang, Hua Cox, Nancy J. Cruz, Miguel Hanis, Craig L. Valladares-Salgado, Adan Sci Rep Article We performed genome-wide meta-analysis of lipid traits on three samples of Mexican and Mexican American ancestry comprising 4,383 individuals, and followed up significant and highly suggestive associations in three additional Hispanic samples comprising 7,876 individuals. Genome-wide significant signals were observed in or near CELSR2, ZNF259/APOA5, KANK2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5, LIPC and CETP for HDL cholesterol, CELSR2, APOB and NCAN/MAU2 for LDL cholesterol, and GCKR, TRIB1, ZNF259/APOA5 and NCAN/MAU2 for triglycerides. Linkage disequilibrium and conditional analyses indicate that signals observed at ABCA1 and LIPC for HDL cholesterol and NCAN/MAU2 for triglycerides are independent of previously reported lead SNP associations. Analyses of lead SNPs from the European Global Lipids Genetics Consortium (GLGC) dataset in our Hispanic samples show remarkable concordance of direction of effects as well as strong correlation in effect sizes. A meta-analysis of the European GLGC and our Hispanic datasets identified five novel regions reaching genome-wide significance: two for total cholesterol (FN1 and SAMM50), two for HDL cholesterol (LOC100996634 and COPB1) and one for LDL cholesterol (LINC00324/CTC1/PFAS). The top meta-analysis signals were found to be enriched for SNPs associated with gene expression in a tissue-specific fashion, suggesting an enrichment of tissue-specific function in lipid-associated loci. Nature Publishing Group 2016-01-19 /pmc/articles/PMC4726092/ /pubmed/26780889 http://dx.doi.org/10.1038/srep19429 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Below, Jennifer E. Parra, Esteban J. Gamazon, Eric R. Torres, Jason Krithika, S. Candille, Sophie Lu, Yingchang Manichakul, Ani Peralta-Romero, Jesus Duan, Qing Li, Yun Morris, Andrew P. Gottesman, Omri Bottinger, Erwin Wang, Xin-Qun Taylor, Kent D. Ida Chen, Y.-D. Rotter, Jerome I. Rich, Stephen S. Loos, Ruth J. F. Tang, Hua Cox, Nancy J. Cruz, Miguel Hanis, Craig L. Valladares-Salgado, Adan Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs |
title | Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs |
title_full | Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs |
title_fullStr | Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs |
title_full_unstemmed | Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs |
title_short | Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs |
title_sort | meta-analysis of lipid-traits in hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eqtls |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4726092/ https://www.ncbi.nlm.nih.gov/pubmed/26780889 http://dx.doi.org/10.1038/srep19429 |
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