The relative contribution of common and rare genetic variants to ADHD

Martin, J. ORCID: https://orcid.org/0000-0002-8911-3479, O'Donovan, M. C. ORCID: https://orcid.org/0000-0001-7073-2379, Thapar, A. ORCID: https://orcid.org/0000-0002-3689-737X, Langley, K. ORCID: https://orcid.org/0000-0002-2033-2657 and Williams, N. ORCID: https://orcid.org/0000-0003-1177-6931 2015. The relative contribution of common and rare genetic variants to ADHD. Translational Psychiatry 5 , e506. 10.1038/tp.2015.5

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Abstract

Attention deficit hyperactivity disorder (ADHD) is highly heritable. Genome-wide molecular studies show an increased burden of large, rare copy-number variants (CNVs) in children with ADHD compared with controls. Recent polygenic risk score analyses have also shown that en masse common variants are enriched in ADHD cases compared with population controls. The relationship between these common and rare variants has yet to be explored. In this study, we tested whether children with ADHD with (N = 60) a large (4500 kb), rare (o1% frequency) CNV differ by polygenic risk scores for ADHD to children with ADHD without such CNVs (N = 421). We also compared ADHD polygenic scores in ADHD children with and without CNVs with a group of population controls (N = 4670; of whom N = 397 had CNVs). The results show that children with ADHD with large, rare CNVs have lower polygenic scores than children without such CNVs (odds ratio (OR) = 0.73, P = 0.023). Although ADHD children without CNVs had higher scores than controls (OR = 1.18, P = 0.0031), this difference was not observed for ADHD children with CNVs (OR = 0.86, P = 0.27). These results are consistent with a polygenic liability threshold model of ADHD with both common and rare variants involved.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Publisher:	Springer Nature
ISSN:	2158-3188
Funders:	Wellcome Trust
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	19 December 2014
Last Modified:	09 May 2023 19:08
URI:	https://orca.cardiff.ac.uk/id/eprint/71977

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