Whole Exome Sequencing to Identify Genetic Variants Associated with Raised Atherosclerotic Lesions in Young Persons

Abstract We investigated the influence of genetic variants on atherosclerosis using whole exome sequencing in cases and controls from the autopsy study “Pathobiological Determinants of Atherosclerosis in Youth (PDAY)”. We identified a PDAY case group with the highest total amounts of raised lesions...

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Autores principales:	James E. Hixson, Goo Jun, Lawrence C. Shimmin, Yizhi Wang, Guoqiang Yu, Chunhong Mao, Andrew S. Warren, Timothy D. Howard, Richard S. Vander Heide, Jennifer Van Eyk, Yue Wang, David M. Herrington
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/485c84a505f64a21bc57f4bf322cab09
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spelling	oai:doaj.org-article:485c84a505f64a21bc57f4bf322cab092021-12-02T12:32:49ZWhole Exome Sequencing to Identify Genetic Variants Associated with Raised Atherosclerotic Lesions in Young Persons10.1038/s41598-017-04433-x2045-2322https://doaj.org/article/485c84a505f64a21bc57f4bf322cab092017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04433-xhttps://doaj.org/toc/2045-2322Abstract We investigated the influence of genetic variants on atherosclerosis using whole exome sequencing in cases and controls from the autopsy study “Pathobiological Determinants of Atherosclerosis in Youth (PDAY)”. We identified a PDAY case group with the highest total amounts of raised lesions (n = 359) for comparisons with a control group with no detectable raised lesions (n = 626). In addition to the standard exome capture, we included genome-wide proximal promoter regions that contain sequences that regulate gene expression. Our statistical analyses included single variant analysis for common variants (MAF > 0.01) and rare variant analysis for low frequency and rare variants (MAF < 0.05). In addition, we investigated known CAD genes previously identified by meta-analysis of GWAS studies. We did not identify individual common variants that reached exome-wide significance using single variant analysis. In analysis limited to 60 CAD genes, we detected strong associations with COL4A2/COL4A1 that also previously showed associations with myocardial infarction and arterial stiffness, as well as coronary artery calcification. Likewise, rare variant analysis did not identify genes that reached exome-wide significance. Among the 60 CAD genes, the strongest association was with NBEAL1 that was also identified in gene-based analysis of whole exome sequencing for early onset myocardial infarction.James E. HixsonGoo JunLawrence C. ShimminYizhi WangGuoqiang YuChunhong MaoAndrew S. WarrenTimothy D. HowardRichard S. Vander HeideJennifer Van EykYue WangDavid M. HerringtonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q James E. Hixson Goo Jun Lawrence C. Shimmin Yizhi Wang Guoqiang Yu Chunhong Mao Andrew S. Warren Timothy D. Howard Richard S. Vander Heide Jennifer Van Eyk Yue Wang David M. Herrington Whole Exome Sequencing to Identify Genetic Variants Associated with Raised Atherosclerotic Lesions in Young Persons
description	Abstract We investigated the influence of genetic variants on atherosclerosis using whole exome sequencing in cases and controls from the autopsy study “Pathobiological Determinants of Atherosclerosis in Youth (PDAY)”. We identified a PDAY case group with the highest total amounts of raised lesions (n = 359) for comparisons with a control group with no detectable raised lesions (n = 626). In addition to the standard exome capture, we included genome-wide proximal promoter regions that contain sequences that regulate gene expression. Our statistical analyses included single variant analysis for common variants (MAF > 0.01) and rare variant analysis for low frequency and rare variants (MAF < 0.05). In addition, we investigated known CAD genes previously identified by meta-analysis of GWAS studies. We did not identify individual common variants that reached exome-wide significance using single variant analysis. In analysis limited to 60 CAD genes, we detected strong associations with COL4A2/COL4A1 that also previously showed associations with myocardial infarction and arterial stiffness, as well as coronary artery calcification. Likewise, rare variant analysis did not identify genes that reached exome-wide significance. Among the 60 CAD genes, the strongest association was with NBEAL1 that was also identified in gene-based analysis of whole exome sequencing for early onset myocardial infarction.
format	article
author	James E. Hixson Goo Jun Lawrence C. Shimmin Yizhi Wang Guoqiang Yu Chunhong Mao Andrew S. Warren Timothy D. Howard Richard S. Vander Heide Jennifer Van Eyk Yue Wang David M. Herrington
author_facet	James E. Hixson Goo Jun Lawrence C. Shimmin Yizhi Wang Guoqiang Yu Chunhong Mao Andrew S. Warren Timothy D. Howard Richard S. Vander Heide Jennifer Van Eyk Yue Wang David M. Herrington
author_sort	James E. Hixson
title	Whole Exome Sequencing to Identify Genetic Variants Associated with Raised Atherosclerotic Lesions in Young Persons
title_short	Whole Exome Sequencing to Identify Genetic Variants Associated with Raised Atherosclerotic Lesions in Young Persons
title_full	Whole Exome Sequencing to Identify Genetic Variants Associated with Raised Atherosclerotic Lesions in Young Persons
title_fullStr	Whole Exome Sequencing to Identify Genetic Variants Associated with Raised Atherosclerotic Lesions in Young Persons
title_full_unstemmed	Whole Exome Sequencing to Identify Genetic Variants Associated with Raised Atherosclerotic Lesions in Young Persons
title_sort	whole exome sequencing to identify genetic variants associated with raised atherosclerotic lesions in young persons
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/485c84a505f64a21bc57f4bf322cab09
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Whole Exome Sequencing to Identify Genetic Variants Associated with Raised Atherosclerotic Lesions in Young Persons

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