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Parent of origin effects in attention/deficit hyperactivity disorder (ADHD): Analysis of data from the international multicenter ADHD genetics (IMAGE) program


Anney, R J L; Hawi, Z; Sheehan, K; Mulligan, A; Pinto, C; Brookes, K J; Xu, X; Zhou, K; Franke, B; Buitelaar, J; Vermeulen, S H; Banaschewski, T; Sonuga-Barke, E; Ebstein, R; Manor, I; Miranda, A; Mulas, F; Oades, R D; Roeyers, H; Rommelse, N; Rothenberger, A; Sergeant, J; Steinhausen, H C; Taylor, E; Thompson, M; Asherson, P; Faraone, S V; Gill, M (2008). Parent of origin effects in attention/deficit hyperactivity disorder (ADHD): Analysis of data from the international multicenter ADHD genetics (IMAGE) program. American Journal of Medical Genetics. Part B, 147B(8):1495-1500.

Abstract

There are conflicting reports suggesting that the parental origin of transmitted risk alleles may play a role in the etiology of attention deficit/hyperactivity disorder (ADHD). A recent report by Hawi and colleagues observed a generalized paternal over-transmission of alleles associated with ADHD. This was not replicated in more recent studies. Using data from a large multicenter study we examined the overall and gene-specific parent of origin effect in 554 independent SNPs across 47 genes. Transmission disequilibrium and explicit parent of origin test were performed using PLINK. Overall parent of origin effect was tested by Chi-square. There was no overall parent of origin effect in the IMAGE sample ($\chi _1;2 = 1.82$, P = 0.117). Five markers in three genes, DDC, TPH2, and SLC6A2 showed nominal association (P < 0.01) with ADHD combined subtype when restricted to maternal or paternal transmission only. Following the initial report by Hawi and co-workers three studies, including this one, found no evidence to support an overall parent of origin effect for markers associated with ADHD. We cannot however, exclude gene-specific parent of origin effect in the etiology ADHD.

There are conflicting reports suggesting that the parental origin of transmitted risk alleles may play a role in the etiology of attention deficit/hyperactivity disorder (ADHD). A recent report by Hawi and colleagues observed a generalized paternal over-transmission of alleles associated with ADHD. This was not replicated in more recent studies. Using data from a large multicenter study we examined the overall and gene-specific parent of origin effect in 554 independent SNPs across 47 genes. Transmission disequilibrium and explicit parent of origin test were performed using PLINK. Overall parent of origin effect was tested by Chi-square. There was no overall parent of origin effect in the IMAGE sample ($\chi _1;2 = 1.82$, P = 0.117). Five markers in three genes, DDC, TPH2, and SLC6A2 showed nominal association (P < 0.01) with ADHD combined subtype when restricted to maternal or paternal transmission only. Following the initial report by Hawi and co-workers three studies, including this one, found no evidence to support an overall parent of origin effect for markers associated with ADHD. We cannot however, exclude gene-specific parent of origin effect in the etiology ADHD.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Child and Adolescent Psychiatry
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:December 2008
Deposited On:08 Jan 2009 16:30
Last Modified:05 Apr 2016 12:37
Publisher:Wiley-Blackwell
ISSN:1552-4841
Publisher DOI:10.1002/ajmg.b.30659
PubMed ID:18163388
Permanent URL: http://doi.org/10.5167/uzh-6561

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