Whole genome analyses suggest ischemic stroke and heart disease share an association with polymorphisms on chromosome 9p21
Whole genome analyses suggest ischemic stroke and heart disease share an association with polymorphisms on chromosome 9p21
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DOI：
10.1161/strokeaha.107.502963
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发表时间：
2008-05-01
期刊：
影响因子：
8.3
通讯作者：
Meschia, James F.
中科院分区：
文献类型：
--
作者：
Matarin, Mar;Brown, W. Mark;Meschia, James F.
背景和目的 - 最近的独立研究报告了冠心病与位于染色体 9p21、CDKN2A 和 CDKN2B 基因附近的单核苷酸多态性 (SNP) 之间的关联。鉴于中风是心肌梗塞后的常见并发症，我们调查了相同的 SNP 是否与我们人群中的缺血性中风相关。方法 - 我们最近启动了缺血性中风的全基因组分析，并发表了使用来自 Illumina Infinium Human-1 和 HumanHap300 检测的超过 400 000 个 SNP 的病例对照研究的第一阶段。我们重点研究了 Helgadotir 及其同事最近与心脏病相关的 SNP，以及来自同一单倍型块的 SNP。结果 - 在针对中风危险因素进行未经调整和调整的分析中，观察到来自先前与心肌梗死相关的同一单倍型块的 SNP 与缺血性中风的显着关联。在涉及这些 SNP 的疾病和单倍型之间也发现了显着关联，无论是否对中风危险因素进行了调整（优势比：1.01 至 2.65）。结论 - 这些数据很重要，原因有 3 个：首先，它们表明与中风存在遗传关联；其次，他们认为这种关联与心脏病和糖尿病有共同的致病机制；第三，他们指出，公开发布数据可以促进快速发现风险点。
Background and Purpose - Recently independent studies reported an association between coronary heart disease and single-nucleotide polymorphisms (SNPs) located at chromosome 9p21, near CDKN2A and CDKN2B genes. Given that stroke is a common complication after myocardial infarction, we investigated if the same SNPs were associated with ischemic stroke in our population.Methods - We recently initiated a whole genome analysis of ischemic stroke and published the first stage of a case control study using > 400 000 SNPs from Illumina Infinium Human-1 and HumanHap300 assays. We focused on SNPs recently associated with heart disease by Helgadottir and colleagues and SNPs from the same haplotype block.Results - In analyses both unadjusted and adjusted for stroke risk factors, significant associations with ischemic stroke were observed for SNPs from the same haplotype block previously associated with myocardial infarction. Significant association was also seen between disease and haplotypes involving these SNPs, both with and without adjustment for stroke risk factors (odd ratios: 1.01 to 2.65).Conclusions - These data are important for 3 reasons: first, they suggest a genetic association for stroke; second, they suggest that this association shares pathogenic mechanisms with heart disease and diabetes; and third, they illustrate, that public release of data can facilitate rapid risk locus discovery.