Does Parental Expressed Emotion Moderate Genetic Effects in ADHD? An Exploration Using a Genome Wide Association Scan
Does Parental Expressed Emotion Moderate Genetic Effects in ADHD? An Exploration Using a Genome Wide Association Scan
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DOI：
10.1002/ajmg.b.30860
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发表时间：
2008-12-05
影响因子：
2.8
通讯作者：
Faraone, Stephen V.
中科院分区：
文献类型：
--
作者：
Sonuga-Barke, Edmund J. S.;Lasky-Su, Jessica;Faraone, Stephen V.
ADHD中基因x环境（G x E）相互作用的研究以前集中在ADHD的已知风险基因和环境介导的生物风险上。在这里，我们使用G x E分析的背景下，全基因组关联扫描，以确定新的基因，其对ADHD症状和共病的行为障碍的影响是由高母亲表达的情绪（EE）缓和。在958个ADHD先证者-父母三人组中对SNP（600，000）进行基因分型。在应用数据清理程序后，我们检查了909个家庭三人组中的429，981个常染色体SNP。ADHD症状的严重程度和共病的行为障碍进行了测量使用的父母帐户的儿童症状访谈。母亲的批评和温暖（即，EE）由独立观察员根据访谈期间的评论进行编码。没有G × E相互作用达到基因组辅助意义。名义上的影响，发现有和没有遗传的主效应。对于具有遗传主效应的那些，36个未校正的相互作用P值< 10（-5），暗示新基因以及一些先前支持的候选基因。这些发现同样经常为所有的相互作用正在调查。观察到的SLC 1A 1和NRG 3 SNP的相互作用代表了合理的候选基因，因为它们以前与几种精神疾病有关。我们发现EE在调节基因对ADHD严重程度和共病行为障碍的影响中的作用的证据，涉及新的和确定的候选人。这些发现需要在更大的独立样本中复制。(c)2008 Wiley-Liss，Inc.
Studies of gene x environment (G x E) interaction in ADHD have previously focused on known risk genes for ADHD and environmentally mediated biological risk. Here we use G x E analysis in the context of a genome-wide association scan to identify novel genes whose effects on ADHD symptoms and comorbid conduct disorder are moderated by high maternal expressed emotion (EE). SNPs (600,000) were genotyped in 958 ADHD proband-parent trios. After applying data cleaning procedures we examined 429,981 autosomal SNPs in 909 family trios. ADHD symptom severity and comorbid conduct disorder was measured using the Parental Account of Childhood Symptoms interview. Maternal criticism and warmth (i.e., EE) were coded by independent observers on comments made during the interview. No G x E interactions reached genome-Aide significance. Nominal effects were found both with and without genetic main effects. For those with genetic main effects 36 uncorrected interaction P-values were < 10(-5) implicating both novel genes as well as some previously supported candidates. These were found equally often for all of the interactions being investigated. The observed interactions in SLC1A1 and NRG3 SNPs represent reasonable candidate genes for further investigation given their previous association with several psychiatric illnesses. We find evidence for the role of EE in moderating the effects of genes on ADHD severity and comorbid conduct disorder, implicating both novel and established candidates. These findings need replicating in larger independent samples. (c) 2008 Wiley-Liss, Inc.