DSM-IV combined type ADHD shows familial association with sibling trait scores: a sampling strategy for QTL linkage.
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.
Chen
Wai
W
MRC Social Genetic Developmental and Psychiatry Centre, Institute of Psychiatry, London, United Kingdom.
Zhou
Kaixin
K
Sham
Pak
P
Franke
Barbara
B
Kuntsi
Jonna
J
Campbell
Desmond
D
Fleischman
Karin
K
Knight
Jo
J
Andreou
Penny
P
Arnold
Renée
R
Altink
Marieke
M
Boer
Frits
F
Boholst
Mary Jane
MJ
Buschgens
Cathelijne
C
Butler
Louise
L
Christiansen
Hanna
H
Fliers
Ellen
E
Howe-Forbes
Raoul
R
Gabriëls
Isabel
I
Heise
Alexander
A
Korn-Lubetzki
Isabelle
I
Marco
Rafaela
R
Medad
She'era
S
Minderaa
Ruud
R
Müller
Ueli C
UC
Mulligan
Aisling
A
Psychogiou
Lamprini
L
Rommelse
Nanda
N
Sethna
Vaheshta
V
Uebel
Henrik
H
McGuffin
Peter
P
Plomin
Robert
R
Banaschewski
Tobias
T
Buitelaar
Jan
J
Ebstein
Richard
R
Eisenberg
Jacques
J
Gill
Michael
M
Manor
Iris
I
Miranda
Ana
A
Mulas
Fernando
F
Oades
Robert D
RD
Roeyers
Herbert
H
Rothenberger
Aribert
A
Sergeant
Joseph
J
Sonuga-Barke
Edmund
E
Steinhausen
Hans-Christoph
HC
Taylor
Eric
E
Thompson
Margaret
M
Faraone
Stephen V
SV
Asherson
Philip
P
D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000235:genetics*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005190:Family; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D007407:Interviews as Topic; D008297:Male; D040641:Quantitative Trait Loci / Q000235:genetics*; D012044:Regression Analysis; D012801:Sibling Relations; D014429:Twins, Dizygotic / Q000235:genetics