Association Study of Nonsynonymous Single Nucleotide Polymorphisms in Schizophrenia
Association Study of Nonsynonymous Single Nucleotide Polymorphisms in Schizophrenia
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DOI：
10.1016/j.biopsych.2011.09.032
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发表时间：
2012-01-15
影响因子：
10.6
通讯作者：
Costas, Javier
中科院分区：
文献类型：
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作者：
Carrera, Noa;Arrojo, Manuel;Costas, Javier
背景：使用数十万个匿名标记的全基因组关联研究呈现出有限的统计功效。或者，仅限于常见的非同义单核苷酸多态性（nsSNP）的关联研究具有极大地减少多重检测问题的优点，同时增加了检测功能性单核苷酸多态性（SNP）的概率。我们对加利西亚人中常见的nsSNPs进行了病例对照关联研究，（西班牙西北部）样品，随后进行更有希望的结果的复制研究。在质量控制程序之后，发现样本由在476名精神分裂症患者和447名对照受试者中分析的次要等位基因频率>5%的5100个nsSNP组成。复制样本包括4069例病例和15，128例欧洲血统的对照受试者。我们还进行了多位点分析，使用nsSNPs在自由显著性阈值和交叉验证程序的汇总得分。
Background: Genome-wide association studies using several hundred thousand anonymous markers present limited statistical power. Alternatively, association studies restricted to common nonsynonymous single nucleotide polymorphisms (nsSNPs) have the advantage of strongly reducing the multiple testing problem, while increasing the probability of testing functional single nucleotide polymorphisms (SNPs).Methods: We performed a case-control association study of common nsSNPs in Galician (northwest Spain) samples using the Affymetrix GeneChip Human 20k cSNP Kit, followed by a replication study of the more promising results. After quality control procedures, the discovery sample consisted of 5100 nsSNPs at minor allele frequency >5% analyzed in 476 schizophrenia patients and 447 control subjects. The replication sample consisted of 4069 cases and 15,128 control subjects of European origin. We also performed multilocus analysis, using aggregated scores of nsSNPs at liberal significance thresholds and cross-validation procedures.Results: The 5 independent nsSNPs with false discovery rate q