TY - JOUR

T1 - DSM-IV combined type ADHD shows familial association with sibling trait scores

T2 - a sampling strategy for QTL linkage

AU - Chen, Wai

AU - Zhou, Kaixin

AU - Sham, Pak

AU - Franke, Barbara

AU - Kuntsi, Jonna

AU - Campbell, Desmond

AU - Fleischman, Karin

AU - Knight, Jo

AU - Andreou, Penny

AU - Arnold, Renée

AU - Altink, Marieke

AU - Boer, Frits

AU - Boholst, Mary Jane

AU - Buschgens, Cathelijne

AU - Butler, Louise

AU - Christiansen, Hanna

AU - Fliers, Ellen

AU - Howe-Forbes, Raoul

AU - Gabriëls, Isabel

AU - Heise, Alexander

AU - Korn-Lubetzki, Isabelle

AU - Marco, Rafaela

AU - Medad, She'era

AU - Minderaa, Ruud

AU - Müller, Ueli C

AU - Mulligan, Aisling

AU - Psychogiou, Lamprini

AU - Rommelse, Nanda

AU - Sethna, Vaheshta

AU - Uebel, Henrik

AU - McGuffin, Peter

AU - Plomin, Robert

AU - Banaschewski, Tobias

AU - Buitelaar, Jan

AU - Ebstein, Richard

AU - Eisenberg, Jacques

AU - Gill, Michael

AU - Manor, Iris

AU - Miranda, Ana

AU - Mulas, Fernando

AU - Oades, Robert D.

AU - Roeyers, Herbert

AU - Rothenberger, Aribert

AU - Sergeant, Joseph

AU - Sonuga-Barke, Edmund

AU - Steinhausen, Hans-Christoph

AU - Taylor, Eric

AU - Thompson, Margaret

AU - Faraone, Stephen V.

AU - Asherson, Philip

N1 - Copyright 2008 Wiley-Liss, Inc.

PY - 2008/12/5

Y1 - 2008/12/5

N2 - 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.

AB - 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.

KW - Attention Deficit Disorder with Hyperactivity

KW - Diagnostic and Statistical Manual of Mental Disorders

KW - Family

KW - Female

KW - Genetic Linkage

KW - Genetic Predisposition to Disease

KW - Humans

KW - Interviews as Topic

KW - Male

KW - Quantitative Trait Loci

KW - Regression Analysis

KW - Sibling Relations

KW - Twins, Dizygotic

U2 - 10.1002/ajmg.b.30672

DO - 10.1002/ajmg.b.30672

M3 - Journal article

C2 - 18189238

VL - 147B

SP - 1450

EP - 1460

JO - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

SN - 1552-4841

IS - 8

ER -