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ADHD and DAT1: Further evidence of paternal over-transmission of risk alleles and haplotype


Hawi, Z; Kent, L; Hill, M; Anney, R J; Brookes, K J; Barry, E; Franke, B; Banaschewski, T; Buitelaar, J; Ebstein, R; Miranda, A; Oades, R D; Roeyers, H; Rothenberger, A; Sergeant, J; Sonuga-Barke, E; Steinhausen, H C; Faraone, S V; Asherson, P; Gill, M (2010). ADHD and DAT1: Further evidence of paternal over-transmission of risk alleles and haplotype. American Journal of Medical Genetics. Part B, 153B(1):97-102.

Abstract

We [Hawi et al. (2005); Am J Hum Genet 77:958-965] reported paternal over-transmission of risk alleles in some ADHD-associated genes. This was particularly clear in the case of the DAT1 3'-UTR VNTR. In the current investigation, we analyzed three new sample comprising of 1,248 ADHD nuclear families to examine the allelic over-transmission of DAT1 in ADHD. The IMAGE sample, the largest of the three-replication samples, provides strong support for a parent of origin effect for allele 6 and the 10 repeat allele (intron 8 and 3'-UTR VNTR, respectively) of DAT1. In addition, a similar pattern of over-transmission of paternal risk haplotypes (constructed from the above alleles) was also observed. Some support is also derived from the two smaller samples although neither is independently significant. Although the mechanism driving the paternal over-transmission of the DAT risk alleles is not known, these finding provide further support for this phenomenon.

We [Hawi et al. (2005); Am J Hum Genet 77:958-965] reported paternal over-transmission of risk alleles in some ADHD-associated genes. This was particularly clear in the case of the DAT1 3'-UTR VNTR. In the current investigation, we analyzed three new sample comprising of 1,248 ADHD nuclear families to examine the allelic over-transmission of DAT1 in ADHD. The IMAGE sample, the largest of the three-replication samples, provides strong support for a parent of origin effect for allele 6 and the 10 repeat allele (intron 8 and 3'-UTR VNTR, respectively) of DAT1. In addition, a similar pattern of over-transmission of paternal risk haplotypes (constructed from the above alleles) was also observed. Some support is also derived from the two smaller samples although neither is independently significant. Although the mechanism driving the paternal over-transmission of the DAT risk alleles is not known, these finding provide further support for this phenomenon.

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16 citations in Web of Science®
16 citations in Scopus®
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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:5 January 2010
Deposited On:10 Aug 2009 13:30
Last Modified:05 Apr 2016 13:19
Publisher:Wiley-Blackwell
ISSN:1552-4841
Additional Information:The definitive version is available at www.blackwell-synergy.com
Publisher DOI:10.1002/ajmg.b.30960
PubMed ID:19388000

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