Ylisaukko-oja Tero, Alarcón Maricela, Cantor Rita M, Auranen Mari, Vanhala Raija, Kempas Elli, von Wendt Lennart, Järvelä Irma, Geschwind Daniel H, Peltonen Leena
Department of Molecular Medicine, National Public Health Institute, University of Helsinki, 00251 Helsinki, Finland.
Ann Neurol. 2006 Jan;59(1):145-55. doi: 10.1002/ana.20722.
Several genome-wide screens have been performed in autism spectrum disorders resulting in the identification of numerous putative susceptibility loci. Analyses of pooled primary data should result in an increased sample size and the different study samples have a potential to strengthen the evidence for some earlier identified loci, reveal novel loci, and even to provide information of the general significance of the locus. The objective of this study was to search for potential susceptibility loci for autism, which are supported by two independent samples.
We performed a combined analysis of the primary genome scan data of the Autism Genetic Resource Exchange (AGRE) and Finnish autism samples to reveal susceptibility loci potentially shared by these study samples.
In the initial combined data analysis, the best loci (p < 0.05) were observed at 1p12-q25, 3p24-26, 4q21-31, 5p15-q12, 6q14-21, 7q33-36, 8q22-24, 17p12-q21, and 19p13-q13. The combined analysis of Finnish and AGRE families showed the most promising shared locus on 3p24-26 with nonparametric logarithm of odds (NPL) score of 2.20 (p = 0.011). The combined data analysis did not provide increased linkage evidence for the earlier identified loci on 3q25-27 or 17p12-q21. However, the 17p12-q21 locus remained promising also in the combined sample (NPL(all) =2.38, p = 0.0076).
Our study of 314 autism families highlights the importance of further analyses on 3p24-26 locus involving comprehensive molecular genetic analyses of oxytocin receptor gene (OXTR), a positional and functional candidate gene for autism.
已针对自闭症谱系障碍进行了多项全基因组筛查，从而鉴定出众多假定的易感基因座。对汇总的原始数据进行分析应能增加样本量，并且不同的研究样本有潜力加强对一些早期鉴定出的基因座的证据支持，揭示新的基因座，甚至提供有关该基因座普遍意义的信息。本研究的目的是寻找由两个独立样本支持的自闭症潜在易感基因座。
我们对自闭症遗传资源交换库（AGRE）和芬兰自闭症样本的原始基因组扫描数据进行了联合分析，以揭示这些研究样本可能共有的易感基因座。
在最初的联合数据分析中，在1p12 - q25、3p24 - 26、4q21 - 31、5p15 - q12、6q14 - 21、7q33 - 36、8q22 - 24、17p12 - q21和19p13 - q13观察到最佳基因座（p < 0.05）。芬兰和AGRE家族的联合分析显示，在3p24 - 26上共享的基因座最具潜力，非参数优势对数（NPL）评分为2.20（p = 0.011）。联合数据分析未为先前在3q25 - 27或17p12 - q21鉴定出的基因座提供更强的连锁证据。然而，17p12 - q21基因座在联合样本中也仍具潜力（NPL（全部）= 2.38，p = 0.0076）。
我们对314个自闭症家庭的研究突出了对3p24 - 26基因座进行进一步分析的重要性，这涉及对催产素受体基因（OXTR）进行全面的分子遗传学分析，OXTR是自闭症的一个位置和功能候选基因。
