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DSM-IV combined type ADHD shows familial association with sibling trait scores: a sampling strategy for QTL linkage

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  • Wai Chen
  • Kaixin Zhou
  • Pak Sham
  • Barbara Franke
  • Jonna Kuntsi
  • Desmond Campbell
  • Karin Fleischman
  • Penny Andreou
  • Renée Arnold
  • Marieke Altink
  • Frits Boer
  • Mary Jane Boholst
  • Cathelijne Buschgens
  • Louise Butler
  • Hanna Christiansen
  • Ellen Fliers
  • Raoul Howe-Forbes
  • Isabel Gabriëls
  • Alexander Heise
  • Isabelle Korn-Lubetzki
  • Rafaela Marco
  • She'era Medad
  • Ruud Minderaa
  • Ueli C Müller
  • Aisling Mulligan
  • Lamprini Psychogiou
  • Nanda Rommelse
  • Vaheshta Sethna
  • Henrik Uebel
  • Peter McGuffin
  • Robert Plomin
  • Tobias Banaschewski
  • Jan Buitelaar
  • Richard Ebstein
  • Jacques Eisenberg
  • Michael Gill
  • Iris Manor
  • Ana Miranda
  • Fernando Mulas
  • Robert D. Oades
  • Herbert Roeyers
  • Aribert Rothenberger
  • Joseph Sergeant
  • Edmund Sonuga-Barke
  • Hans-Christoph Steinhausen
  • Eric Taylor
  • Margaret Thompson
  • Stephen V. Faraone
  • Philip Asherson
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<mark>Journal publication date</mark>5/12/2008
<mark>Journal</mark>American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Issue number8
Volume147B
Number of pages11
Pages (from-to)1450-1460
Publication StatusPublished
Early online date11/01/08
<mark>Original language</mark>English

Abstract

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 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.