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Genetic heterogeneity in ADHD: DAT1 gene only affects probands without CD
Author(s) -
Zhou Kaixin,
Chen Wai,
Buitelaar Jan,
Banaschewski Tobias,
Oades Robert D.,
Franke Barbara,
SonugaBarke Edmund,
Ebstein Richard,
Eisenberg Jacques,
Gill Michael,
Manor Iris,
Miranda Ana,
Mulas Fernando,
Roeyers Herbert,
Rothenberger Aribert,
Sergeant Joseph,
Steinhausen HansChristoph,
LaskySu Jessica,
Taylor Eric,
Brookes Keeley J.,
Xu Xiaohui,
Neale Benjamin M.,
Rijsdijk Fruhling,
Thompson Margaret,
Asherson Philip,
Faraone Stephen V.
Publication year - 2007
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30644
Subject(s) - proband , attention deficit hyperactivity disorder , genetic heterogeneity , genetics , single nucleotide polymorphism , psychology , comorbidity , genotype , endophenotype , association test , genetic association , phenotype , biology , gene , clinical psychology , psychiatry , mutation , cognition
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. © 2007 Wiley‐Liss, Inc.