Genetic Heterogeneity in ADHD: DAT1 Gene Only Affects Probands Without CD

被引：27

作者：

Zhou, Kaixin ^{[2
]}

Chen, Wai ^{[2
]}

Buitelaar, Jan ^{[3
]}

Banaschewski, Tobias ^{[4
,5
]}

Oades, Robert D. ^{[6
]}

Franke, Barbara ^{[3
,7
]}

Sonuga-Barke, Edmund J. S. ^{[8
]}

Ebstein, Richard ^{[9
]}

Eisenberg, Jacques ^{[10
]}

Gill, Michael ^{[11
]}

Manor, Iris ^{[9
]}

Miranda, Ana ^{[12
]}

Mulas, Fernando ^{[12
]}

Roeyers, Herbert ^{[13
]}

Rothenberger, Aribert ^{[4
]}

Sergeant, Joseph ^{[14
]}

Steinhausen, Hans-Christoph ^{[15
]}

Lasky-Su, Jessica ^{[1
,16
,17
]}

Taylor, Eric ^{[2
]}

Brookes, Keeley J. ^{[2
]}

Xu, Xiaohui ^{[2
]}

Neale, Benjamin M. ^{[2
,18
,19
,20
]}

Rijsdijk, Fruhling ^{[2
]}

Thompson, Margaret ^{[8
]}

Asherson, Philip ^{[2
]}

Faraone, Stephen V. ^{[1
,16
,17
]}

机构：

[1] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA

[2] Inst Psychiat, MRC, Social Genet Dev & Psychiat Ctr, London, England

[3] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, NL-6525 ED Nijmegen, Netherlands

[4] Univ Gottingen, D-3400 Gottingen, Germany

[5] Cent Inst Mental Hlth, Dept Child & Adolescent Psychiat & Psychotherapy, D-6800 Mannheim, Germany

[6] Univ Clin Child & Adolescent Psychiat, Essen, Germany

[7] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands

[8] Univ Southampton, Sch Psychol, Southampton, Hants, England

[9] Geha Mental Hlth Ctr, ADHD Clin, Petah Tiqwa, Israel

[10] S Herzog Mem Hosp, Jerusalem, Israel

[11] St James Hosp, Trinity Ctr Hlth Sci, Dept Psychiat, Dublin 8, Ireland

[12] Univ Valencia, Dept Dev & Educ Psychol, E-46003 Valencia, Spain

[13] Univ Ghent, B-9000 Ghent, Belgium

[14] Vrije Univ Amsterdam, Dept Clin Neuropsychol, Amsterdam, Netherlands

[15] Univ Zurich, Dept Child & Adolescent Psychiat, CH-8006 Zurich, Switzerland

[16] SUNY Upstate Med Univ, Dept Neurosci, Syracuse, NY 13210 USA

[17] SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY 13210 USA

[18] Broad Inst Harvard, Cambridge, MA USA

[19] MIT, Cambridge, MA 02139 USA

[20] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS | 2008年 / 147B卷 / 08期

关键词：

comorbidity; stratification; association;

D O I：

10.1002/ajmg.b.30644

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1481 / 1487

页数：7

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