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全基因组关联研究行为障碍症状学。

Genome-wide association study of conduct disorder symptomatology.

机构信息

Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.

出版信息

Mol Psychiatry. 2011 Aug;16(8):800-8. doi: 10.1038/mp.2010.73. Epub 2010 Jun 29.

Abstract

Conduct disorder (CD) is one of the most prevalent childhood psychiatric conditions, and is associated with a number of serious concomitant and future problems. CD symptomatology is known to have a considerable genetic component, with heritability estimates in the range of 50%. Despite this, there is a relative paucity of studies aimed at identifying genes involved in the susceptibility to CD. In this study, we report results from a genome-wide association study of CD symptoms. CD symptoms were retrospectively reported by a psychiatric interview among a sample of cases and controls, in which cases met the criteria for alcohol dependence. Our primary phenotype was the natural log transformation of the number of CD symptoms that were endorsed, with data available for 3963 individuals who were genotyped on the Illumina Human 1M beadchip array. Secondary analyses are presented for case versus control status, in which caseness was established as endorsing three or more CD symptoms (N = 872 with CD and N = 3091 without CD). We find four markers that meet the criteria for genome-wide significance (P<5 × 10(-8)) with the CD symptom count, two of which are located in the gene C1QTNF7 (C1q and tumor necrosis factor-related protein 7). There were six additional SNPs in the gene that yielded converging evidence of association. These data provide the first evidence of a specific gene that is associated with CD symptomatology. None of the top signals resided in traditional candidate genes, underscoring the importance of a genome-wide approach for identifying novel variants involved in this serious childhood disorder.

摘要

品行障碍(CD)是最常见的儿童精神疾病之一,与许多严重的伴随和未来问题有关。CD 的症状学已知具有相当大的遗传成分,遗传率估计在 50%左右。尽管如此,旨在确定易患 CD 的相关基因的研究相对较少。在这项研究中,我们报告了一项针对 CD 症状的全基因组关联研究的结果。CD 症状通过对病例和对照组进行的精神病学访谈进行回顾性报告,其中病例符合酒精依赖的标准。我们的主要表型是被认可的 CD 症状数量的自然对数转换,有 3963 名个体的数据可用于在 Illumina Human 1M 珠芯片阵列上进行基因分型,这些个体被基因分型。呈现了针对病例与对照状态的二次分析,其中病例被确定为认可三个或更多 CD 症状(N = 872 个有 CD 和 N = 3091 个没有 CD)。我们发现了四个符合 CD 症状计数全基因组显著水平(P < 5 × 10(-8))的标记,其中两个位于 C1QTNF7 基因(C1q 和肿瘤坏死因子相关蛋白 7)中。该基因中还有六个 SNP 具有关联的汇聚证据。这些数据提供了与 CD 症状学相关的特定基因的第一个证据。没有一个顶级信号位于传统的候选基因中,强调了全基因组方法在鉴定涉及这种严重儿童疾病的新变体方面的重要性。

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