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DSM‐IV combined type ADHD shows familial association with sibling trait scores: A sampling strategy for QTL linkage
Author(s) -
Chen Wai,
Zhou Kaixin,
Sham Pak,
Franke Barbara,
Kuntsi Jonna,
Campbell Desmond,
Fleischman Karin,
Knight Jo,
Andreou Penny,
Arnold Renée,
Altink Marieke,
Boer Frits,
Boholst Mary Jane,
Buschgens Cathelijne,
Butler Louise,
Christiansen Hanna,
Fliers Ellen,
HoweForbes Raoul,
Gabriëls Isabel,
Heise Alexander,
KornLubetzki Isabelle,
Marco Rafaela,
Medad She'era,
Minderaa Ruud,
Müller Ueli C.,
Mulligan Aisling,
Psychogiou Lamprini,
Rommelse Nanda,
Sethna Vaheshta,
Uebel Henrik,
McGuffin Peter,
Plomin Robert,
Banaschewski Tobias,
Buitelaar Jan,
Ebstein Richard,
Eisenberg Jacques,
Gill Michael,
Manor Iris,
Miranda Ana,
Mulas Fernando,
Oades Robert D.,
Roeyers Herbert,
Rothenberger Aribert,
Sergeant Joseph,
SonugaBarke Edmund,
Steinhausen HansChristoph,
Taylor Eric,
Thompson Margaret,
Faraone Stephen V.,
Asherson Philip
Publication year - 2008
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.30672
Subject(s) - sibling , quantitative trait locus , impulsivity , proband , attention deficit hyperactivity disorder , twin study , population , trait , psychology , genetic association , clinical psychology , genetics , developmental psychology , medicine , biology , heritability , genotype , single nucleotide polymorphism , computer science , mutation , gene , programming language , environmental health
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 (λ 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 ADHD 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. © 2008 Wiley‐Liss, Inc.