Analysis of gene-gene interactions among common variants in candidate cardiovascular genes in coronary artery disease.
Analysis of gene-gene interactions among common variants in candidate cardiovascular genes in coronary artery disease.
复制标题
冠状动脉疾病候选心血管基因常见变异之间的基因-基因相互作用分析。
DOI：
10.1371/journal.pone.0117684
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Tomaszewski M
中科院分区：
文献类型：
--
作者：
Musameh MD;Wang WY;Nelson CP;Lluís-Ganella C;Debiec R;Subirana I;Elosua R;Balmforth AJ;Ball SG;Hall AS;Kathiresan S;Thompson JR;Lucas G;Samani NJ;Tomaszewski M
迄今为止，只有一小部分冠状动脉疾病（CAD）的遗传性可以用常见的变异来解释。对心血管调节重要的基因之间的相互作用可能解释了CAD遗传性缺失的部分原因。本研究旨在探讨冠心病候选心血管基因常见变异中基因-基因相互作用的作用。来自英国心脏基金会家庭心脏研究的2，101名CAD患者和2，426名无CAD对照被纳入发现队列。所有受试者均使用富集了与心血管系统和疾病相关的基因和途径的Illumina HumanCVD BeadChip进行基因分型。发现队列中的主要分析检查了913个常见（次要等位基因频率>0.1）独立单核苷酸多态性（SNP）之间的成对相互作用，这些SNP在单基因座分析中至少与CAD存在名义关联。在所有11，332个独立的共同SNP中进行二次探索性相互作用分析，这些SNP符合质量控制标准。在来自心肌梗死遗传学联盟的2,967名患者和3,075名对照中进行了重复分析。在多重检验校正后，初步分析中分析的913个SNP之间的相互作用均无统计学显著性（要求P<1.2x10-7）。同样，在多重检验校正后，次要分析中的成对基因-基因相互作用均未达到统计学显著性（要求P = 7.8x10-10）。在复制队列中，主要分析的36种提示性相互作用或次要分析的31种相互作用均不显著。我们的研究在主要分析中有80%的能力检测出常见变异的优势比> 1.7。心血管疾病相关基因中常见SNPs之间的适度大的加性相互作用似乎在CAD的遗传易感性中没有发挥主要作用。不太常见的SNPs之间的遗传相互作用的作用和中等和小幅度的影响仍有待研究。
Only a small fraction of coronary artery disease (CAD) heritability has been explained by common variants identified to date. Interactions between genes of importance to cardiovascular regulation may account for some of the missing heritability of CAD. This study aimed to investigate the role of gene-gene interactions in common variants in candidate cardiovascular genes in CAD. 2,101 patients with CAD from the British Heart Foundation Family Heart Study and 2,426 CAD-free controls were included in the discovery cohort. All subjects were genotyped with the Illumina HumanCVD BeadChip enriched for genes and pathways relevant to the cardiovascular system and disease. The primary analysis in the discovery cohort examined pairwise interactions among 913 common (minor allele frequency >0.1) independent single nucleotide polymorphisms (SNPs) with at least nominal association with CAD in single locus analysis. A secondary exploratory interaction analysis was performed among all 11,332 independent common SNPs surviving quality control criteria. Replication analyses were conducted in 2,967 patients and 3,075 controls from the Myocardial Infarction Genetics Consortium. None of the interactions amongst 913 SNPs analysed in the primary analysis was statistically significant after correction for multiple testing (required P<1.2x10-7). Similarly, none of the pairwise gene-gene interactions in the secondary analysis reached statistical significance after correction for multiple testing (required P = 7.8x10-10). None of 36 suggestive interactions from the primary analysis or 31 interactions from the secondary analysis was significant in the replication cohort. Our study had 80% power to detect odds ratios > 1.7 for common variants in the primary analysis. Moderately large additive interactions between common SNPs in genes relevant to cardiovascular disease do not appear to play a major role in genetic predisposition to CAD. The role of genetic interactions amongst less common SNPs and with medium and small magnitude effects remain to be investigated.
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DOI：
10.1038/nrg2579
发表时间：
2009-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Cordell HJ
通讯作者：
Cordell HJ
影响因子：
4.5
作者：
Ma L;Brautbar A;Boerwinkle E;Sing CF;Clark AG;Keinan A
通讯作者：
Keinan A
影响因子：
4.6
作者：
Lippert, Christoph;Listgarten, Jennifer;Davidson, Robert I.;Baxter, Scott;Poong, Hoifung;Kadie, Carl M.;Heckerman, David
通讯作者：
Heckerman, David
DOI：
10.1056/nejmoa072366
发表时间：
2007-08-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Samani NJ;Erdmann J;Hall AS;Hengstenberg C;Mangino M;Mayer B;Dixon RJ;Meitinger T;Braund P;Wichmann HE;Barrett JH;König IR;Stevens SE;Szymczak S;Tregouet DA;Iles MM;Pahlke F;Pollard H;Lieb W;Cambien F;Fischer M;Ouwehand W;Blankenberg S;Balmforth AJ;Baessler A;Ball SG;Strom TM;Braenne I;Gieger C;Deloukas P;Tobin MD;Ziegler A;Thompson JR;Schunkert H;WTCCC and the Cardiogenics Consortium
通讯作者：
WTCCC and the Cardiogenics Consortium
影响因子：
5.8
作者：
Herold, Christine;Steffens, Michael;Becker, Tim
通讯作者：
Becker, Tim