Neale Benjamin M, Lasky-Su Jessica, Anney Richard, Franke Barbara, Zhou Kaixin, Maller Julian B, Vasquez Alejandro Arias, Asherson Philip, Chen Wai, Banaschewski Tobias, Buitelaar Jan, Ebstein Richard, Gill Michael, Miranda Ana, Oades Robert D, Roeyers Herbert, Rothenberger Aribert, Sergeant Joseph, Steinhausen Hans Christoph, Sonuga-Barke Edmund, Mulas Fernando, Taylor Eric, Laird Nan, Lange Christoph, Daly Mark, Faraone Stephen V
Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK.
Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5;147B(8):1337-44. doi: 10.1002/ajmg.b.30866.
Results of behavioral genetic and molecular genetic studies have converged to suggest that genes substantially contribute to the development of attention deficit/hyperactivity disorder (ADHD), a common disorder with an onset in childhood. Yet, despite numerous linkage and candidate gene studies, strongly consistent and replicable association has eluded detection. To search for ADHD susceptibility genes, we genotyped approximately 600,000 SNPs in 958 ADHD affected family trios. After cleaning the data, we analyzed 438,784 SNPs in 2,803 individuals comprising 909 complete trios using ADHD diagnosis as phenotype. We present the initial TDT findings as well as considerations for cleaning family-based TDT data. None of the SNP association tests achieved genome-wide significance, indicating that larger samples may be required to identify risk loci for ADHD. We additionally identify a systemic bias in family-based association, and suggest that variable missing genotype rates may be the source of this bias.
行为遗传学和分子遗传学研究结果趋于一致,表明基因在注意缺陷多动障碍(ADHD)的发展中起重要作用,ADHD是一种常见的儿童期起病的疾病。然而,尽管进行了大量的连锁和候选基因研究,但尚未发现强烈一致且可重复的关联。为了寻找ADHD易感基因,我们对958个受ADHD影响的三联体家庭中的约60万个单核苷酸多态性(SNP)进行了基因分型。在清理数据后,我们以ADHD诊断为表型,对2803名个体(包括909个完整三联体)中的438,784个SNP进行了分析。我们展示了最初的传递不平衡检验(TDT)结果以及清理基于家庭的TDT数据的注意事项。没有一个SNP关联测试达到全基因组显著性,这表明可能需要更大的样本量来识别ADHD的风险位点。我们还发现了基于家庭的关联中的一种系统性偏差,并表明可变的缺失基因型率可能是这种偏差的来源。