A genome-wide scan for common alleles affecting risk for autism.

Publication authors did not provide a list of Subject IDs used in this publication, cohorts in this study consist of all subjects with SNP genotyping data deposited with NDAR under data-set 8133.

Publication Abstract:
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.

该出版物的作者未提供本研究中使用的受试者ID列表，本研究的队列由所有在NDAR数据库数据集8133下提交了单核苷酸多态性（SNP）基因分型数据的受试者组成。

出版物摘要：
尽管自闭症谱系障碍（ASDs）具有显著的遗传基础，但大多数已知的遗传风险已被追溯至罕见变异，主要是拷贝数变异（CNVs）。为识别常见风险变异，自闭症基因组计划（AGP）联盟对1558个严格定义的自闭症谱系障碍（ASD）家庭进行了100万个单核苷酸多态性（SNP）基因分型，并分析了这些SNP基因型与ASD的关联性。在四项主要关联分析中的一项中，位于MACROD2基因内的标记rs4141463的关联信号超过了全基因组关联显著性阈值（P <5×10⁻⁸）。在分析较小的复制样本时，rs4141463位点的风险等位基因再次过度传递；然而，与胜者诅咒一致，其在复制样本中的效应量显著减小；并且，在合并样本中，关联信号刚好低于P <5×10⁻⁸的阈值。对表型亚型的探索性分析在多重检验校正后未发现显著关联。不过，这些分析在KIAA0564、PLD5、POU6F2、ST8SIA2和TAF1C等多个基因中产生了强信号。