Genome-Wide Linkage Analysis of Large Multiple Multigenerational Families Identifies Novel Genetic Loci for Coronary Artery Disease

Abstract Coronary artery disease (CAD) is the leading cause of death, and genetic factors contribute significantly to risk of CAD. This study aims to identify new CAD genetic loci through a large-scale linkage analysis of 24 large and multigenerational families with 433 family members (GeneQuest II)...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yang Guo, Fan Wang, Lin Li, Hanxiang Gao, Stephen Arckacki, Isabel Z. Wang, John Barnard, Stephen Ellis, Carlos Hubbard, Eric J. Topol, Qiuyun Chen, Qing K. Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/19d7af9badc641428546028580f0c1f1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:19d7af9badc641428546028580f0c1f1
record_format	dspace
spelling	oai:doaj.org-article:19d7af9badc641428546028580f0c1f12021-12-02T15:05:14ZGenome-Wide Linkage Analysis of Large Multiple Multigenerational Families Identifies Novel Genetic Loci for Coronary Artery Disease10.1038/s41598-017-05381-22045-2322https://doaj.org/article/19d7af9badc641428546028580f0c1f12017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05381-2https://doaj.org/toc/2045-2322Abstract Coronary artery disease (CAD) is the leading cause of death, and genetic factors contribute significantly to risk of CAD. This study aims to identify new CAD genetic loci through a large-scale linkage analysis of 24 large and multigenerational families with 433 family members (GeneQuest II). All family members were genotyped with markers spaced by every 10 cM and a model-free nonparametric linkage (NPL-all) analysis was carried out. Two highly significant CAD loci were identified on chromosome 17q21.2 (NPL score of 6.20) and 7p22.2 (NPL score of 5.19). We also identified four loci with significant NPL scores between 4.09 and 4.99 on 2q33.3, 3q29, 5q13.2 and 9q22.33. Similar analyses in individual families confirmed the six significant CAD loci and identified seven new highly significant linkages on 9p24.2, 9q34.2, 12q13.13, 15q26.1, 17q22, 20p12.3, and 22q12.1, and two significant loci on 2q11.2 and 11q14.1. Two loci on 3q29 and 9q22.33 were also successfully replicated in our previous linkage analysis of 428 nuclear families. Moreover, two published risk variants, SNP rs46522 in UBE2Z and SNP rs6725887 in WDR12 by GWAS, were found within the 17q21.2 and 2q33.3 loci. These studies lay a foundation for future identification of causative variants and genes for CAD.Yang GuoFan WangLin LiHanxiang GaoStephen ArckackiIsabel Z. WangJohn BarnardStephen EllisCarlos HubbardEric J. TopolQiuyun ChenQing K. WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yang Guo Fan Wang Lin Li Hanxiang Gao Stephen Arckacki Isabel Z. Wang John Barnard Stephen Ellis Carlos Hubbard Eric J. Topol Qiuyun Chen Qing K. Wang Genome-Wide Linkage Analysis of Large Multiple Multigenerational Families Identifies Novel Genetic Loci for Coronary Artery Disease
description	Abstract Coronary artery disease (CAD) is the leading cause of death, and genetic factors contribute significantly to risk of CAD. This study aims to identify new CAD genetic loci through a large-scale linkage analysis of 24 large and multigenerational families with 433 family members (GeneQuest II). All family members were genotyped with markers spaced by every 10 cM and a model-free nonparametric linkage (NPL-all) analysis was carried out. Two highly significant CAD loci were identified on chromosome 17q21.2 (NPL score of 6.20) and 7p22.2 (NPL score of 5.19). We also identified four loci with significant NPL scores between 4.09 and 4.99 on 2q33.3, 3q29, 5q13.2 and 9q22.33. Similar analyses in individual families confirmed the six significant CAD loci and identified seven new highly significant linkages on 9p24.2, 9q34.2, 12q13.13, 15q26.1, 17q22, 20p12.3, and 22q12.1, and two significant loci on 2q11.2 and 11q14.1. Two loci on 3q29 and 9q22.33 were also successfully replicated in our previous linkage analysis of 428 nuclear families. Moreover, two published risk variants, SNP rs46522 in UBE2Z and SNP rs6725887 in WDR12 by GWAS, were found within the 17q21.2 and 2q33.3 loci. These studies lay a foundation for future identification of causative variants and genes for CAD.
format	article
author	Yang Guo Fan Wang Lin Li Hanxiang Gao Stephen Arckacki Isabel Z. Wang John Barnard Stephen Ellis Carlos Hubbard Eric J. Topol Qiuyun Chen Qing K. Wang
author_facet	Yang Guo Fan Wang Lin Li Hanxiang Gao Stephen Arckacki Isabel Z. Wang John Barnard Stephen Ellis Carlos Hubbard Eric J. Topol Qiuyun Chen Qing K. Wang
author_sort	Yang Guo
title	Genome-Wide Linkage Analysis of Large Multiple Multigenerational Families Identifies Novel Genetic Loci for Coronary Artery Disease
title_short	Genome-Wide Linkage Analysis of Large Multiple Multigenerational Families Identifies Novel Genetic Loci for Coronary Artery Disease
title_full	Genome-Wide Linkage Analysis of Large Multiple Multigenerational Families Identifies Novel Genetic Loci for Coronary Artery Disease
title_fullStr	Genome-Wide Linkage Analysis of Large Multiple Multigenerational Families Identifies Novel Genetic Loci for Coronary Artery Disease
title_full_unstemmed	Genome-Wide Linkage Analysis of Large Multiple Multigenerational Families Identifies Novel Genetic Loci for Coronary Artery Disease
title_sort	genome-wide linkage analysis of large multiple multigenerational families identifies novel genetic loci for coronary artery disease
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/19d7af9badc641428546028580f0c1f1
work_keys_str_mv	AT yangguo genomewidelinkageanalysisoflargemultiplemultigenerationalfamiliesidentifiesnovelgeneticlociforcoronaryarterydisease AT fanwang genomewidelinkageanalysisoflargemultiplemultigenerationalfamiliesidentifiesnovelgeneticlociforcoronaryarterydisease AT linli genomewidelinkageanalysisoflargemultiplemultigenerationalfamiliesidentifiesnovelgeneticlociforcoronaryarterydisease AT hanxianggao genomewidelinkageanalysisoflargemultiplemultigenerationalfamiliesidentifiesnovelgeneticlociforcoronaryarterydisease AT stephenarckacki genomewidelinkageanalysisoflargemultiplemultigenerationalfamiliesidentifiesnovelgeneticlociforcoronaryarterydisease AT isabelzwang genomewidelinkageanalysisoflargemultiplemultigenerationalfamiliesidentifiesnovelgeneticlociforcoronaryarterydisease AT johnbarnard genomewidelinkageanalysisoflargemultiplemultigenerationalfamiliesidentifiesnovelgeneticlociforcoronaryarterydisease AT stephenellis genomewidelinkageanalysisoflargemultiplemultigenerationalfamiliesidentifiesnovelgeneticlociforcoronaryarterydisease AT carloshubbard genomewidelinkageanalysisoflargemultiplemultigenerationalfamiliesidentifiesnovelgeneticlociforcoronaryarterydisease AT ericjtopol genomewidelinkageanalysisoflargemultiplemultigenerationalfamiliesidentifiesnovelgeneticlociforcoronaryarterydisease AT qiuyunchen genomewidelinkageanalysisoflargemultiplemultigenerationalfamiliesidentifiesnovelgeneticlociforcoronaryarterydisease AT qingkwang genomewidelinkageanalysisoflargemultiplemultigenerationalfamiliesidentifiesnovelgeneticlociforcoronaryarterydisease
_version_	1718388876709462016

Genome-Wide Linkage Analysis of Large Multiple Multigenerational Families Identifies Novel Genetic Loci for Coronary Artery Disease

Ejemplares similares