DSM-IV Combined Type ADHD Shows Familial Association With Sibling Trait Scores: A Sampling Strategy For QTL Linkage

被引：113

作者：

Chen, Wai ^{[1
]}

Zhou, Kaixin ^{[1
]}

Sham, Pak ^{[1
,2
]}

Franke, Barbara ^{[3
,4
]}

Kuntsi, Jonna ^{[1
]}

Campbell, Desmond ^{[1
]}

Fleischman, Karin ^{[1
]}

Knight, Jo ^{[1
]}

Andreou, Penny ^{[1
]}

Arnold, Renee ^{[5
]}

Altink, Marieke ^{[3
]}

Boer, Frits ^{[6
]}

Boholst, Mary Jane ^{[1
]}

Buschgens, Catheljjne ^{[3
]}

Butler, Louise ^{[7
]}

Christiansen, Hanna ^{[8
]}

Fliers, Ellen ^{[3
,9
]}

Howe-Forbes, Raoul ^{[1
]}

Gabriels, Isabel ^{[10
]}

Heise, Alexander ^{[11
]}

Korn-Lubetzki, Isabelle ^{[12
]}

Marco, Rafaela ^{[13
]}

Medad, She'era ^{[14
]}

Minderaa, Ruud ^{[15
]}

Mueller, Ueli C. ^{[16
]}

Mulligan, Aisling ^{[7
]}

Psychogiou, Lamprini ^{[17
]}

Rommelse, Nanda ^{[18
]}

Sethna, Vaheshta ^{[1
]}

Uebel, Henrik ^{[11
]}

McGuffin, Peter ^{[1
]}

Plomin, Robert ^{[1
]}

Banaschewski, Tobias ^{[11
,19
]}

Buitelaar, Jan ^{[3
]}

Ebstein, Richard ^{[20
]}

Eisenberg, Jacques ^{[20
]}

Gill, Michael ^{[7
]}

Manor, Iris ^{[14
]}

Miranda, Ana ^{[13
]}

Mulas, Fernando ^{[21
]}

Oades, Robert D. ^{[8
]}

Roeyers, Herbert ^{[10
]}

Rothenberger, Aribert ^{[11
]}

Sergeant, Joseph ^{[18
]}

Sonuga-Barke, Edmund J. S. ^{[17
]}

Steinhausen, Hans-Christoph ^{[16
]}

Taylor, Eric ^{[1
]}

Thompson, Margaret ^{[17
]}

Faraone, Stephen V. ^{[22
,23
]}

Asherson, Philip ^{[1
]}

机构：

[1] Inst Psychiat, MRC, Social Genet Dev & Psychiat Ctr, London SE5 8AF, England

[2] Univ Hong Kong, LKS Fac Med, Dept Psychiat, Pokfulam, Hong Kong, Peoples R China

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

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

[5] Ctr Child & Adolescent Psychiat, Triversam, Alkmaar, Netherlands

[6] Amsterdam Med Ctr Bascule, Amsterdam, Netherlands

[7] Trinity Coll Dublin, Sch Med, Neuropsychiat Genet Res Grp, Dublin, Ireland

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

[9] BAVO Europoort, Rotterdam, Netherlands

[10] Univ Ghent, Dept Expt Clin & Hlth Psychol, Ghent, Belgium

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

[12] Shaare Zedek Med Ctr, Jerusalem, Israel

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

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

[15] Univ Groningen, Univ Med Ctr Groningen, Univ Ctr Child & Adolescence Psychiat, NL-9713 AV Groningen, Netherlands

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

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

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

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

[20] S Herzog Mem Hosp, Jerusalem, Israel

[21] Univ Hosp La Fe, Neuropediat Serv, Valencia, Spain

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

[23] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA

来源：

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

基金：

英国医学研究理事会;

关键词：

attention deficit hyperactivity disorder (ADHD); quantitative trait locus (QTL); linkage study; quantitative genetics; DF analysis;

D O I：

10.1002/ajmg.b.30672

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Attention deficit hyperactivity disorder (ADHD) is a discrete clinical syndrome characterized by the triad of inattention, hyperactivity, and impulsivity in the context of marked impairments. Molecular genetic studies have been successful in identifying genetic variants associated with ADHD, particularly with DSM-IV inattentive and combined subtypes. Quantitative trait locus (QTL) approaches to linkage and association mapping have yet to be widely used in ADHD research, although twin studies investigating individual differences suggest that genetic liability for ADHD is continuously distributed throughout the population, underscoring the applicability of quantitative dimensional approaches. To investigate the appropriateness: of QTL approaches, we tested the familial association between 894 probands with a research diagnosis of DSM-IV ADHD combined type and continuous trait measures among 1,135 of their siblings unselected for phenotype. The sibling recurrence rate for ADHD combined subtype was 12.7%, yielding a sibling recurrence risk ratio (lambda(sib)) of 9.0. Estimated sibling correlations around 0.2-0.3 are similar to those estimated from the analysis of fraternal twins in population twin samples. We further show that there are no threshold effects on the sibling risk for ADHD among the ADHD probands; and that both affected and unaffected siblings contributed to the association with ADRD trait scores. In conclusion, these data confirm the main requirement for QTL mapping of ADHD by demonstrating that narrowly defined DSM-IV combined type probands show familial association with dimensional ADHD symptom scores amongst their siblings. (c) 2008 Wiley-Liss, Inc.

引用

页码：1450 / 1460

页数：11

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