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

ABSTRACT: 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?

SUBMITTER: Brevik EJ

PROVIDER: S-EPMC5071721 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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

Brevik Erlend J EJ van Donkelaar Marjolein M J MM Weber Heike H Sánchez-Mora Cristina C Jacob Christian C Rivero Olga O Kittel-Schneider Sarah S Garcia-Martínez Iris I Aebi Marcel M van Hulzen Kimm K Cormand Bru B Ramos-Quiroga Josep A JA Lesch Klaus-Peter KP Reif Andreas A Ribasés Marta M Franke Barbara B Posserud Maj-Britt MB Johansson Stefan S Lundervold Astri J AJ Haavik Jan J Zayats Tetyana T

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20160329 5

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 ex ...[more]

PMID: 27021288

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Project description:BackgroundAttention deficit hyperactivity disorder (ADHD) is a highly heritable neuropsychiatric condition, but it has been difficult to identify genes underlying this disorder. This study aimed to explore genetics of ADHD in an ethnically homogeneous Norwegian population by means of a genome-wide association (GWA) analysis followed by examination of candidate loci.Materials and methodsParticipants were recruited through Norwegian medical and birth registries as well as the general population. Presence of ADHD was defined according to DSM-IV criteria. Genotyping was performed using Illumina Human OmniExpress-12v1 microarrays. Statistical analyses were divided into several steps: (1) genome-wide association in the form of logistic regression in PLINK and follow-up pathway analyses performed in DAPPLE and INRICH softwares, (2) SNP-heritability calculated using genome-wide complex trait analysis (GCTA) tool, (3) gene-based association tests carried out in JAG software, and (4) evaluation of previously reported genome-wide signals and candidate genes of ADHD.ResultsIn total, 1.358 individuals (478 cases and 880 controls) and 598.384 autosomal SNPs were subjected to GWA analysis. No single polymorphism reached genome-wide significance. The strongest signal was observed at rs9949006 in the ENSG00000263745 gene (OR=1.51, 95% CI 1.28-1.79, p=1.38E-06). Pathway analyses of the top SNPs implicated genes involved in the regulation of gene expression, cell adhesion and inflammation. Among previously identified ADHD candidate genes, prominent association signals were observed for SLC9A9 (rs1393072, OR=1.46, 95% CI = 1.21-1.77, p=9.95E-05) and TPH2 (rs17110690, OR = 1.38, 95% CI = 1.14-1.66, p=8.31E-04).ConclusionThis study confirms the complexity and heterogeneity of ADHD etiology. Taken together with previous findings, our results point to a spectrum of biological mechanisms underlying the symptoms of ADHD, providing targets for further genetic exploration of this complex disorder.

Dataset Information

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

Publications

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

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