GWAS for discovery and replication of genetic loci associated with sudden cardiac arrest in patients with coronary artery disease.
GWAS for discovery and replication of genetic loci associated with sudden cardiac arrest in patients with coronary artery disease.
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DOI：
10.1186/1471-2261-11-29
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发表时间：
2011-06-10
影响因子：
2.1
通讯作者：
Tseng ZH
中科院分区：
文献类型：
--
作者：
Aouizerat BE;Vittinghoff E;Musone SL;Pawlikowska L;Kwok PY;Olgin JE;Tseng ZH
流行病学证据表明，心脏骤停的风险与心肌梗死的风险无关，这是一个可遗传的组成部分。最近关于社区心脏骤停的候选基因关联研究集中在有限数量的生物学途径上，并产生了相互矛盾的结果。我们试图通过进行全基因组关联研究来确定与冠状动脉疾病患者心脏骤停相关的新基因。在一项病例对照研究中，对89例冠心病患者和520名健康对照组进行了跨越基因组的标记SNP(n=338,328)的分型。7个基因(ACYP2、AP1G2、ESR1、DGES2、GRIA1、KCTD1ZNF385B)中有7个SNPs与心脏骤停(全部P<；1.30×10-7)相关；ESR1基因变异(P=2.62×10-8；优势比[OR]=1.43，95%可信区间[CI]：1.277，1.596)已被确定为心血管疾病的危险因素。随后，对单基因长QT间期综合征(LQT1-9)的9个基因的作用进行了评估，得出了与CACNA1C相关的证据(LQT8；p=3.0 9×10-4；OR=1.18，95%CI：1.079，1.290)。我们还评估了最近发表的4个与心脏骤停有关的基因，证实了NOS1AP(p=4.5×10-2，OR=1.15，95%CI：1.003，1.326)、CSMD2(p=6.6×10-3，OR=2.27，95%CI：1.681，2.859)和AGTR1(p=3.00×10-3，OR=1.13，95%CI：1.042，1.215)。我们证明了11个基因与冠状动脉疾病患者室性心动过速/室颤引起的心脏骤停有关。需要在独立队列中进行验证研究和功能研究来确认这些关联。
Epidemiologic evidence suggests a heritable component to risk for sudden cardiac arrest independent of risk for myocardial infarction. Recent candidate gene association studies for community sudden cardiac arrests have focused on a limited number of biological pathways and yielded conflicting results. We sought to identify novel gene associations for sudden cardiac arrest in patients with coronary artery disease by performing a genome-wide association study. Tagging SNPs (n = 338,328) spanning the genome were typed in a case-control study comparing 89 patients with coronary artery disease and sudden cardiac arrest due to ventricular tachycardia or ventricular fibrillation to 520 healthy controls. Fourteen SNPs including 7 SNPs among 7 genes (ACYP2, AP1G2, ESR1, DGES2, GRIA1, KCTD1, ZNF385B) were associated with sudden cardiac arrest (all p < 1.30 × 10-7), following Bonferroni correction and adjustment for population substructure, age, and sex; genetic variation in ESR1 (p = 2.62 × 10-8; Odds Ratio [OR] = 1.43, 95% confidence interval [CI]:1.277, 1.596) has previously been established as a risk factor for cardiovascular disease. In tandem, the role of 9 genes for monogenic long QT syndrome (LQT1-9) was assessed, yielding evidence of association with CACNA1C (LQT8; p = 3.09 × 10-4; OR = 1.18, 95% CI:1.079, 1.290). We also assessed 4 recently published gene associations for sudden cardiac arrest, validating NOS1AP (p = 4.50 × 10-2, OR = 1.15, 95% CI:1.003, 1.326), CSMD2 (p = 6.6 × 10-3, OR = 2.27, 95% CI:1.681, 2.859), and AGTR1 (p = 3.00 × 10-3, OR = 1.13, 95% CI:1.042, 1.215). We demonstrate 11 gene associations for sudden cardiac arrest due to ventricular tachycardia/ventricular fibrillation in patients with coronary artery disease. Validation studies in independent cohorts and functional studies are required to confirm these associations.
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影响因子：
3.7
作者：
Arking, Dan E.;Reinier, Kyndaron;Chugh, Sumeet S.
通讯作者：
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DOI：
10.1073/pnas.0709118105
发表时间：
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影响因子：
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作者：
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