Genome-wide analyses of aggressiveness in attention-deficit hyperactivity disorder

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• 作者：Erlend J. Brevik ; Marjolein M. J. van Donkelaar ; Heike Weber ; Cristina Sá ; nchez-Mora ; Christian Jacob ; Olga Rivero ; Sarah Kittel-Schneider ; Iris Garcia-Martí ; nez ; Marcel Aebi ; Kimm van Hulzen ; Bru Cormand ; Josep A. Ramos-Quiroga ; IMAGE Consortium ; Klaus-Peter Lesch ; Andreas Reif ; Marta Ribasé ; s ; Barbara Franke ; Maj-Britt Posserud ; Stefan Johansson ; Astri J. Lundervold ; Jan Haavik and Tetyana Zayats
• 刊名：American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：171
• 期：5
• 页码：733-747
• 全文大小：2435K
• ISSN：1552-485X

文摘

Aggressiveness is a behavioral trait that has the potential to be harmful to individuals and society. With an estimated heritability of about 40%, genetics is important in its development. We performed an exploratory genome-wide association (GWA) analysis of childhood aggressiveness in attention deficit hyperactivity disorder (ADHD) to gain insight into the underlying biological processes associated with this trait. Our primary sample consisted of 1,060 adult ADHD patients (aADHD). To further explore the genetic architecture of childhood aggressiveness, we performed enrichment analyses of suggestive genome-wide associations observed in aADHD among GWA signals of dimensions of oppositionality (defiant/vindictive and irritable dimensions) in childhood ADHD (cADHD). No single polymorphism reached genome-wide significance (P < 5.00E-08). The strongest signal in aADHD was observed at rs10826548, within a long noncoding RNA gene (beta = −1.66, standard error (SE) = 0.34, P = 1.07E-06), closely followed by rs35974940 in the neurotrimin gene (beta = 3.23, SE = 0.67, P = 1.26E-06). The top GWA SNPs observed in aADHD showed significant enrichment of signals from both the defiant/vindictive dimension (Fisher's P-value = 2.28E-06) and the irritable dimension in cADHD (Fisher's P-value = 0.0061). In sum, our results identify a number of biologically interesting markers possibly underlying childhood aggressiveness and provide targets for further genetic exploration of aggressiveness across psychiatric disorders.