TY - JOUR
T1 - Genetic heterogeneity in ADHD
T2 - DAT1 gene only affects probands without CD
AU - Zhou, Kaixin
AU - Chen, Wai
AU - Buitelaar, Jan
AU - Banaschewski, Tobias
AU - Oades, Robert D.
AU - Franke, Barbara
AU - Sonuga-Barke, Edmund
AU - Ebstein, Richard
AU - Eisenberg, Jacques
AU - Gill, Michael
AU - Manor, Iris
AU - Miranda, Ana
AU - Mulas, Fernando
AU - Roeyers, Herbert
AU - Rothenberger, Aribert
AU - Sergeant, Joseph
AU - Steinhausen, Hans Christoph
AU - Lasky-Su, Jessica
AU - Taylor, Eric
AU - Brookes, Keeley J.
AU - Xu, Xiaohui
AU - Neale, Benjamin M.
AU - Rijsdijk, Fruhling
AU - Thompson, Margaret
AU - Asherson, Philip
AU - Faraone, Stephen V.
PY - 2008/12/5
Y1 - 2008/12/5
N2 - 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.
AB - 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.
KW - Association
KW - Comorbidity
KW - Stratification
UR - http://www.scopus.com/inward/record.url?scp=57349088306&partnerID=8YFLogxK
U2 - 10.1002/ajmg.b.30644
DO - 10.1002/ajmg.b.30644
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C2 - 18553640
AN - SCOPUS:57349088306
SN - 1552-4841
VL - 147
SP - 1481
EP - 1487
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 8
ER -