Siblings with ischemic stroke study: results of a genome-wide scan for stroke loci.
Siblings with ischemic stroke study: results of a genome-wide scan for stroke loci.
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DOI：
10.1161/strokeaha.111.620484
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发表时间：
2011-10
期刊：
影响因子：
8.3
通讯作者：
Siblings With Ischemic Stroke Study Investigators
中科院分区：
文献类型：
--
作者：
Meschia JF;Nalls M;Matarin M;Brott TG;Brown RD Jr;Hardy J;Kissela B;Rich SS;Singleton A;Hernandez D;Ferrucci L;Pearce K;Keller M;Worrall BB;Siblings With Ischemic Stroke Study Investigators
缺血性中风有很强的家族性风险。缺血性卒中兄弟姐妹研究（SWISS）是一项基于全基因组的家庭分析，包括使用输入的基因型。SWISS研究了snp与卒中风险和卒中亚型之间的关系。SWISS在美国和加拿大的70个中心招募了312名缺血性卒中先证患者。受影响的兄弟姐妹由中心确定，并经中心记录审查确认；通过电话联系确定未受影响的兄弟姐妹。用TOAST标准分型缺血性卒中。使用Illumina 610四元阵列（先证者）和Illumina连锁V阵列（受影响的兄弟姐妹）进行基因分型。使用1000 Genomes Project数据和MACH软件进行snp的计算。采用兄弟姐妹传播不平衡检验进行基于家庭的关联分析。对于所有对，受影响的兄弟姐妹之间中风年龄的相关性为r = 0.83 （95%CI, 0.78 ~ 0.86; P < 2.2×10−16）。这种相关性在不同亚型之间没有显著差异。卒中亚型在受影响的对之间的一致性为33.8% (kappa = 0.13; P = 5.06×10−4)，且在先证者的卒中年龄上没有差异。尽管没有SNP对缺血性卒中风险具有全基因组意义，但在染色体3p （NOS1）和6p上存在最相关的SNP聚类。卒中亚型和卒中年龄在受影响的兄弟姐妹中表现出显著的聚集性。没有个体SNP达到全基因组意义。然而，确定了两个有希望的候选基因座，包括一个含有NOS1的基因座，尽管这些风险基因座需要在更大的样本收集中进一步检查。
Ischemic stroke has a strong familial component to risk. The Siblings with Ischemic Stroke Study (SWISS) is a genome-wide family-based analysis that included use of imputed genotypes. SWISS was conducted to examine associations between SNPs and risk of stroke and stroke subtypes within pairs. SWISS enrolled 312 probands with ischemic stroke across 70 US and Canadian centers. Affected siblings were ascertained by centers and confirmed by central record review; unaffected siblings were ascertained by telephone contact. Ischemic stroke was subtyped using TOAST criteria. Genotyping was performed using an Illumina 610 quad array (probands) and an Illumina linkage V array (affected siblings). SNPs were imputed using 1000 Genomes Project data and MACH software. Family-based association analyses were conducted using the sibling-transmission disequilibrium test. For all pairs, the correlation of age at stroke within pairs of affected siblings was r = 0.83 (95%CI, 0.78 to 0.86; P < 2.2×10−16). The correlation did not differ substantially by subtype. The concordance of stroke subtypes among affected pairs was 33.8% (kappa = 0.13; P = 5.06×10−4) and did not differ by age at stroke in the proband. Although no SNP achieved genome-wide significance for risk of ischemic stroke, there was clustering of the most associated SNPs on chromosomes 3p (NOS1) and 6p. Stroke subtype and age at stroke in affected sibling pairs exhibit significant clustering. No individual SNP reached genome-wide significance. However, two promising candidate loci were identified, including one that contains NOS1, though these risk loci warrant further examination in larger sample collections.