No Association Between a Common Single Nucleotide Polymorphism, rs4141463, in the MACROD2 Gene and Autism Spectrum Disorder
No Association Between a Common Single Nucleotide Polymorphism, rs4141463, in the MACROD2 Gene and Autism Spectrum Disorder
复制标题
DOI：
10.1002/ajmg.b.31201
复制
发表时间：
2011-09-01
影响因子：
2.8
通讯作者：
Collier, David
中科院分区：
文献类型：
--
作者：
Curran, Sarah;Bolton, Patrick;Collier, David
自闭症基因组计划（AGP）联盟最近报道了自闭症与MACROD 2基因内的内含子单核苷酸多态性标记rs 4141463之间的全基因组显著关联。在本研究中，我们试图使用一个独立的病例对照设计来复制这一发现，该设计包括来自欧洲五个中心（英国、德国、荷兰、意大利和冰岛）的1,170例自闭症谱系障碍（ASD）病例（其中874例符合自闭症（A）的狭义标准）和35,307例对照。合并样本量为我们提供了11.9的非中心性参数（NCP），在α为0.05时检测rs 4141463等位基因关联的把握度为93%，比值比为0.84（AGP联盟数据的最佳比值比估计值），对于自闭症的狭义诊断，NCP为8.9，把握度为85%。我们对病例对照数据进行关联分析，按每个中心分层，并使用荟萃分析程序GWAMA合并汇总统计量。这导致ASD的比值比（OR）为1.03（95% CI 0.944-1.133），P值为0.5，自闭症（A）亚组的OR为0.99（95% CI 0.88-1.11），P值= 0.85。因此，这项研究并不支持rs 4141463与自闭症之间的关联。(C)2011 Wiley-Liss，Inc.
The Autism Genome Project (AGP) Consortium recently reported genome-wide significant association between autism and an intronic single nucleotide polymorphism marker, rs4141463, within the MACROD2 gene. In the present study we attempted to replicate this finding using an independent case-control design of 1,170 cases with autism spectrum disorder (ASD) (874 of which fulfilled narrow criteria for Autism (A)) from five centers within Europe (UK, Germany, the Netherlands, Italy, and Iceland), and 35,307 controls. The combined sample size gave us a non-centrality parameter (NCP) of 11.9, with 93% power to detect allelic association of rs4141463 at an alpha of 0.05 with odds ratio of 0.84 (the best odds ratio estimate of the AGP Consortium data), and for the narrow diagnosis of autism, an NCP of 8.9 and power of 85%. Our case-control data were analyzed for association, stratified by each center, and the summary statistics were combined using the meta-analysis program, GWAMA. This resulted in an odds ratio (OR) of 1.03 (95% CI 0.944-1.133), with a P-value of 0.5 for ASD and OR of 0.99 (95% CI 0.88-1.11) with P-value = 0.85 for the Autism(A) sub-group. Therefore, this study does not provide support for the reported association between rs4141463 and autism. (C) 2011 Wiley-Liss, Inc.