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Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia
Recent genome-wide association studies (GWAS) have identified multiple loci associated with coronary artery disease (CAD) among predominantly Europeans. However, their relevance to multi-ethnic populations from Southeast Asia is largely unknown. We performed a meta-analysis of four GWAS comprising t...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738399/ https://www.ncbi.nlm.nih.gov/pubmed/29263402 http://dx.doi.org/10.1038/s41598-017-18214-z |
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author | Han, Yi Dorajoo, Rajkumar Chang, Xuling Wang, Ling Khor, Chiea-Chuen Sim, Xueling Cheng, Ching-Yu Shi, Yuan Tham, Yih Chung Zhao, Wanting Chee, Miao Ling Sabanayagam, Charumathi Chee, Miao Li Tan, Nicholas Wong, Tien Yin Tai, E-Shyong Liu, Jianjun Goh, Daniel Y. T. Yuan, Jian-Min Koh, Woon-Puay van Dam, Rob M. Low, Adrian F. Chan, Mark Yan-Yee Friedlander, Yechiel Heng, Chew-Kiat |
author_facet | Han, Yi Dorajoo, Rajkumar Chang, Xuling Wang, Ling Khor, Chiea-Chuen Sim, Xueling Cheng, Ching-Yu Shi, Yuan Tham, Yih Chung Zhao, Wanting Chee, Miao Ling Sabanayagam, Charumathi Chee, Miao Li Tan, Nicholas Wong, Tien Yin Tai, E-Shyong Liu, Jianjun Goh, Daniel Y. T. Yuan, Jian-Min Koh, Woon-Puay van Dam, Rob M. Low, Adrian F. Chan, Mark Yan-Yee Friedlander, Yechiel Heng, Chew-Kiat |
author_sort | Han, Yi |
collection | PubMed |
description | Recent genome-wide association studies (GWAS) have identified multiple loci associated with coronary artery disease (CAD) among predominantly Europeans. However, their relevance to multi-ethnic populations from Southeast Asia is largely unknown. We performed a meta-analysis of four GWAS comprising three Chinese studies and one Malay study (Total N = 2,169 CAD cases and 7,376 controls). Top hits (P < 5 × 10(−8)) were further evaluated in 291 CAD cases and 1,848 controls of Asian Indians. Using all datasets, we validated recently identified loci associated with CAD. The involvement of known canonical pathways in CAD was tested by Ingenuity Pathway Analysis. We identified a missense SNP (rs2075291, G > T, G185C) in APOA5 for CAD that reached robust genome-wide significance (Meta P = 7.09 × 10(−10), OR = 1.636). Conditional probability analysis indicated that the association at rs2075291 was independent of previously reported index SNP rs964184 in APOA5. We further replicated 10 loci previously identified among predominantly Europeans (P: 1.33 × 10(−7)–0.047). Seven pathways (P: 1.10 × 10(−5)–0.019) were identified. We identified a missense SNP, rs2075291, in APOA5 associated with CAD at a genome-wide significance level and provided new insights into pathways contributing to the susceptibility to CAD in the multi-ethnic populations from Southeast Asia. |
format | Online Article Text |
id | pubmed-5738399 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57383992017-12-22 Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia Han, Yi Dorajoo, Rajkumar Chang, Xuling Wang, Ling Khor, Chiea-Chuen Sim, Xueling Cheng, Ching-Yu Shi, Yuan Tham, Yih Chung Zhao, Wanting Chee, Miao Ling Sabanayagam, Charumathi Chee, Miao Li Tan, Nicholas Wong, Tien Yin Tai, E-Shyong Liu, Jianjun Goh, Daniel Y. T. Yuan, Jian-Min Koh, Woon-Puay van Dam, Rob M. Low, Adrian F. Chan, Mark Yan-Yee Friedlander, Yechiel Heng, Chew-Kiat Sci Rep Article Recent genome-wide association studies (GWAS) have identified multiple loci associated with coronary artery disease (CAD) among predominantly Europeans. However, their relevance to multi-ethnic populations from Southeast Asia is largely unknown. We performed a meta-analysis of four GWAS comprising three Chinese studies and one Malay study (Total N = 2,169 CAD cases and 7,376 controls). Top hits (P < 5 × 10(−8)) were further evaluated in 291 CAD cases and 1,848 controls of Asian Indians. Using all datasets, we validated recently identified loci associated with CAD. The involvement of known canonical pathways in CAD was tested by Ingenuity Pathway Analysis. We identified a missense SNP (rs2075291, G > T, G185C) in APOA5 for CAD that reached robust genome-wide significance (Meta P = 7.09 × 10(−10), OR = 1.636). Conditional probability analysis indicated that the association at rs2075291 was independent of previously reported index SNP rs964184 in APOA5. We further replicated 10 loci previously identified among predominantly Europeans (P: 1.33 × 10(−7)–0.047). Seven pathways (P: 1.10 × 10(−5)–0.019) were identified. We identified a missense SNP, rs2075291, in APOA5 associated with CAD at a genome-wide significance level and provided new insights into pathways contributing to the susceptibility to CAD in the multi-ethnic populations from Southeast Asia. Nature Publishing Group UK 2017-12-20 /pmc/articles/PMC5738399/ /pubmed/29263402 http://dx.doi.org/10.1038/s41598-017-18214-z Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Han, Yi Dorajoo, Rajkumar Chang, Xuling Wang, Ling Khor, Chiea-Chuen Sim, Xueling Cheng, Ching-Yu Shi, Yuan Tham, Yih Chung Zhao, Wanting Chee, Miao Ling Sabanayagam, Charumathi Chee, Miao Li Tan, Nicholas Wong, Tien Yin Tai, E-Shyong Liu, Jianjun Goh, Daniel Y. T. Yuan, Jian-Min Koh, Woon-Puay van Dam, Rob M. Low, Adrian F. Chan, Mark Yan-Yee Friedlander, Yechiel Heng, Chew-Kiat Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia |
title | Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia |
title_full | Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia |
title_fullStr | Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia |
title_full_unstemmed | Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia |
title_short | Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia |
title_sort | genome-wide association study identifies a missense variant at apoa5 for coronary artery disease in multi-ethnic cohorts from southeast asia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738399/ https://www.ncbi.nlm.nih.gov/pubmed/29263402 http://dx.doi.org/10.1038/s41598-017-18214-z |
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