Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Stergiakouli, Evangelia; Hamshere, Marian; Holmans, Peter; Langley, Kate; Zaharieva, Irina; Hawi, Ziarah; Kent, Lindsey; Gill, Michael; Williams, Nigel; Owen, Michael J; O'Donovan, Michael; Thapar, Anita (2012). Investigating the contribution of common genetic variants to the risk and pathogenesis of ADHD. American Journal of Psychiatry, 169(2):186-194.

Full text not available from this repository.

View at publisher

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.

Citations

38 citations in Web of Science®
40 citations in Scopus®
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Child and Adolescent Psychiatry
DDC:610 Medicine & health
Language:German
Date:2012
Deposited On:04 Apr 2012 07:47
Last Modified:27 Nov 2013 20:42
Publisher:American Psychiatric Publishing
ISSN:0002-953X
Publisher DOI:10.1176/appi.ajp.2011.11040551
PubMed ID:22420046

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page