A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.
A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.
复制标题
对冠状动脉疾病进行基于 1,000 个基因组的全面全基因组关联荟萃分析。
DOI：
10.1038/ng.3396
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发表时间：
2015-10
期刊：
影响因子：
30.8
通讯作者：
Farrall M
中科院分区：
文献类型：
--
作者：
Nikpay M;Goel A;Won HH;Hall LM;Willenborg C;Kanoni S;Saleheen D;Kyriakou T;Nelson CP;Hopewell JC;Webb TR;Zeng L;Dehghan A;Alver M;Armasu SM;Auro K;Bjonnes A;Chasman DI;Chen S;Ford I;Franceschini N;Gieger C;Grace C;Gustafsson S;Huang J;Hwang SJ;Kim YK;Kleber ME;Lau KW;Lu X;Lu Y;Lyytikäinen LP;Mihailov E;Morrison AC;Pervjakova N;Qu L;Rose LM;Salfati E;Saxena R;Scholz M;Smith AV;Tikkanen E;Uitterlinden A;Yang X;Zhang W;Zhao W;de Andrade M;de Vries PS;van Zuydam NR;Anand SS;Bertram L;Beutner F;Dedoussis G;Frossard P;Gauguier D;Goodall AH;Gottesman O;Haber M;Han BG;Huang J;Jalilzadeh S;Kessler T;König IR;Lannfelt L;Lieb W;Lind L;Lindgren CM;Lokki ML;Magnusson PK;Mallick NH;Mehra N;Meitinger T;Memon FU;Morris AP;Nieminen MS;Pedersen NL;Peters A;Rallidis LS;Rasheed A;Samuel M;Shah SH;Sinisalo J;Stirrups KE;Trompet S;Wang L;Zaman KS;Ardissino D;Boerwinkle E;Borecki IB;Bottinger EP;Buring JE;Chambers JC;Collins R;Cupples LA;Danesh J;Demuth I;Elosua R;Epstein SE;Esko T;Feitosa MF;Franco OH;Franzosi MG;Granger CB;Gu D;Gudnason V;Hall AS;Hamsten A;Harris TB;Hazen SL;Hengstenberg C;Hofman A;Ingelsson E;Iribarren C;Jukema JW;Karhunen PJ;Kim BJ;Kooner JS;Kullo IJ;Lehtimäki T;Loos RJF;Melander O;Metspalu A;März W;Palmer CN;Perola M;Quertermous T;Rader DJ;Ridker PM;Ripatti S;Roberts R;Salomaa V;Sanghera DK;Schwartz SM;Seedorf U;Stewart AF;Stott DJ;Thiery J;Zalloua PA;O'Donnell CJ;Reilly MP;Assimes TL;Thompson JR;Erdmann J;Clarke R;Watkins H;Kathiresan S;McPherson R;Deloukas P;Schunkert H;Samani NJ;Farrall M
关于影响冠状动脉疾病(CAD)风险的遗传变异的现有知识主要基于对常见SNPs的全基因组关联研究(GWAS)分析。利用1000基因组计划的阶段性单倍型，我们报告了对18.5万例冠心病病例和对照的GWAS荟萃分析，询问了670万个常见(MAF0.05)和270万个低频(0.005；MAF0.05)变异。除了确认大多数已知的CAD基因座外，我们还鉴定了10个新的基因座，其中8个是加性的，2个是隐性的，它们包含了新的与管壁生物学过程有关的候选基因。我们观察到基因座内等位基因的异质性，但很少有证据表明低频变异具有更大的影响，也没有证据表明合成关联。我们的分析对冠心病的精细遗传结构进行了全面的调查，表明对这种常见疾病的遗传易感性在很大程度上是由效应大小较小的常见SNP决定的。
Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.