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Genetic heterogeneity in ADHD: DAT1 gene only affects probands without CD


Zhou, K; Chen, W; Buitelaar, J; Banaschewski, T; Oades, R D; Franke, B; Sonuga-Barke, E; Ebstein, R; Eisenberg, J; Gill, M; Manor, I; Miranda, A; Mulas, F; Roeyers, H; Rothenberger, A; Sergeant, J; Steinhausen, H C; Lasky-Su, J; Taylor, E; Brookes, K J; Xu, X; Neale, B M; Rijsdijk, F; Thompson, M; Asherson, P; Faraone, S V (2008). Genetic heterogeneity in ADHD: DAT1 gene only affects probands without CD. American Journal of Medical Genetics. Part B, 147B(8):1481-1487.

Abstract

Previous studies have found heterogeneous association between DAT1-3'-UTR-VNTR and attention deficit hyperactivity disorder (ADHD). Various proportions of conduct disorder (CD) comorbidity in their ADHD samples may partially explain the observational discrepancies. Evidence for this comes from family and twin studies which found ADHD probands with CD (ADHD + CD) are genetically different from those without CD (ADHD - CD). Genotypes of 20 DAT1 markers were analyzed in 576 trios, consisting of 141 ADHD + CD and 435 ADHD - CD. In addition to the classical TDT test, a specific genetic heterogeneity test was performed to identify variants that have different transmission patterns in the two phenotypic subgroups. After multiple-test correction, rs40184 and rs2652511 were significant in TDT tests. Further heterogeneity test found the two SNPs had a significant transmission pattern difference between ADHD + CD and ADHD - CD children, indicating that DAT1 has a significantly greater genetic influence on ADHD without CD. Although the result needs further replications, it does highlight the importance of selecting genetically homogeneous samples for molecular genetic analyses of ADHD. (c) 2007 Wiley-Liss, Inc.

Previous studies have found heterogeneous association between DAT1-3'-UTR-VNTR and attention deficit hyperactivity disorder (ADHD). Various proportions of conduct disorder (CD) comorbidity in their ADHD samples may partially explain the observational discrepancies. Evidence for this comes from family and twin studies which found ADHD probands with CD (ADHD + CD) are genetically different from those without CD (ADHD - CD). Genotypes of 20 DAT1 markers were analyzed in 576 trios, consisting of 141 ADHD + CD and 435 ADHD - CD. In addition to the classical TDT test, a specific genetic heterogeneity test was performed to identify variants that have different transmission patterns in the two phenotypic subgroups. After multiple-test correction, rs40184 and rs2652511 were significant in TDT tests. Further heterogeneity test found the two SNPs had a significant transmission pattern difference between ADHD + CD and ADHD - CD children, indicating that DAT1 has a significantly greater genetic influence on ADHD without CD. Although the result needs further replications, it does highlight the importance of selecting genetically homogeneous samples for molecular genetic analyses of ADHD. (c) 2007 Wiley-Liss, Inc.

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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 December 2008
Deposited On:12 Dec 2008 11:00
Last Modified:05 Apr 2016 12:37
Publisher:Wiley-Blackwell
ISSN:1552-4841
Publisher DOI:10.1002/ajmg.b.30644
PubMed ID:18553640
Permanent URL: http://doi.org/10.5167/uzh-6559

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