Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Investigating the contribution of common genetic variants to the risk and pathogenesis of ADHD

Stergiakouli, Evangelia, Hamshere, Marian Lindsay, Holmans, Peter Alan, Langley, Kate, Zaharieva, Irina, Hawi, Ziarah, Kent, Lindsey, Gill, Michael, Williams, Nigel Melville, Owen, Michael John, O'Donovan, Michael Conlon and Thapar, Anita 2012. Investigating the contribution of common genetic variants to the risk and pathogenesis of ADHD. American Journal of Psychiatry 169 (2) , pp. 186-194. 10.1176/appi.ajp.2011.11040551

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution Non-commercial.

Download (246kB) | Preview

Abstract

Objective: A major motivation for seeking disease-associated genetic variation is to identify novel risk processes. Although rare copy number variants (CNVs) appear to contribute to attention deficit hyperactivity disorder (ADHD), common risk variants (single-nucleotide polymorphisms [SNPs]) have not yet been detected using genome-wide association studies (GWAS). This raises the concern as to whether future larger-scale, adequately powered GWAS will be worthwhile. The authors undertook a GWAS of ADHD and examined whether associated SNPs, including those below conventional levels of significance, influenced the same biological pathways affected by CNVs. Method: The authors analyzed genome-wide SNP frequencies in 727 children with ADHD and 5,081 comparison subjects. The gene sets that were enriched in a pathway analysis of the GWAS data (the top 5% of SNPs) were tested for an excess of genes spanned by large, rare CNVs in the children with ADHD. Results: No SNP achieved genome-wide significance levels. As previously reported in a subsample of the present study, large, rare CNVs were significantly more common in case subjects than comparison subjects. Thirteen biological pathways enriched for SNP association significantly overlapped with those enriched for rare CNVs. These included cholesterol-related and CNS development pathways. At the level of individual genes, CHRNA7, which encodes a nicotinic receptor subunit previously implicated in neuropsychiatric disorders, was affected by six large duplications in case subjects (none in comparison subjects), and SNPs in the gene had a gene-wide p value of 0.0002 for association in the GWAS. Conclusions: Both common and rare genetic variants appear to be relevant to ADHD and index-shared biological pathways.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Advanced Research Computing @ Cardiff (ARCCA)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Systems Immunity Research Institute (SIURI)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: American Psychiatric Publishing
ISSN: 0002-953X
Funders: Wellcome Trust, MRC
Date of First Compliant Deposit: 30 March 2016
Last Modified: 08 May 2019 22:02
URI: http://orca.cf.ac.uk/id/eprint/30256

Citation Data

Cited 148 times in Google Scholar. View in Google Scholar

Cited 128 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics