Genome-Wide Linkage Scan Identifies Two Novel Genetic Loci for Coronary Artery Disease: In GeneQuest Families

doi:10.1371/journal.pone.0113935

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	Genome-Wide Linkage Scan Identifies Two Novel Genetic Loci for Coronary Artery Disease: In GeneQuest Families
	Gao, H; Li, L; Rao, SQ; Shen, GQ; Xi, QS; Chen, SH; Zhang, Z; Wang, K; Ellis, SG; Chen, QY
刊名	PLOS ONE
	2014-12-08
卷号	9 期号:12 页码:-
ISSN号	1932-6203
DOI	10.1371/journal.pone.0113935
文献子类	Article
英文摘要	Coronary artery disease (CAD) is the leading cause of death worldwide. Recent genome-wide association studies (GWAS) identified >50 common variants associated with CAD or its complication myocardial infarction (MI), but collectively they account for <20% of heritability, generating a phenomena of "missing heritability''. Rare variants with large effects may account for a large portion of missing heritability. Genome-wide linkage studies of large families and follow-up fine mapping and deep sequencing are particularly effective in identifying rare variants with large effects. Here we show results from a genome-wide linkage scan for CAD in multiplex GeneQuest families with early onset CAD and MI. Whole genome genotyping was carried out with 408 markers that span the human genome by every 10 cM and linkage analyses were performed using the affected relative pair analysis implemented in GENEHUNTER. Affected only nonparametric linkage (NPL) analysis identified two novel CAD loci with highly significant evidence of linkage on chromosome 3p25.1 (peak NPL =5.49) and 3q29 (NPL =6.84). We also identified four loci with suggestive linkage on 9q22.33, 9q34.11, 17p12, and 21q22.3 (NPL = 3.18-4.07). These results identify novel loci for CAD and provide a framework for fine mapping and deep sequencing to identify new susceptibility genes and novel variants associated with risk of CAD.
学科主题	Science & Technology - Other Topics
出版地	SAN FRANCISCO
资助项目	国家自然科学基金项目 ; 美国国立卫生研究院项目
项目编号	National Institute of Health grants [R01 HL121358, R01 HL094498, P50 HL77107] ; American Heart Association grants [0630193N, 11SDG5510001, 11IRG5570046] ; National Natural Science Foundation of China [31071166, 81373085] ; Science and Technology Planning Project of Guangdong Province [2009A030301004]
语种	英语
WOS记录号	WOS:000346907600030
资助机构	NSFC ; NIH
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/125904]
专题	第一临床医学院_期刊论文
通讯作者	Topol, EJ (reprint author), Scripps Res Inst, Scripps Translat Sci Inst, Scripps Clin, La Jolla, CA 92037 USA.
推荐引用方式 GB/T 7714	Gao, H,Li, L,Rao, SQ,et al. Genome-Wide Linkage Scan Identifies Two Novel Genetic Loci for Coronary Artery Disease: In GeneQuest Families[J]. PLOS ONE,2014,9(12):-.
APA	Gao, H.,Li, L.,Rao, SQ.,Shen, GQ.,Xi, QS.,...&Topol, EJ .(2014).Genome-Wide Linkage Scan Identifies Two Novel Genetic Loci for Coronary Artery Disease: In GeneQuest Families.PLOS ONE,9(12),-.
MLA	Gao, H,et al."Genome-Wide Linkage Scan Identifies Two Novel Genetic Loci for Coronary Artery Disease: In GeneQuest Families".PLOS ONE 9.12(2014):-.