Linkage to chromosome 1p36 for attention-deficit/hyperactivity disorder traits in school and home settings.
BACKGROUND
Limited success has been achieved through previous attention-deficit/hyperactivity disorder (ADHD) linkage scans, which were all designed to map genes underlying the dichotomous phenotype. The International Multi-centre ADHD Genetics (IMAGE) project performed a whole genome linkage scan specifically designed to map ADHD quantitative trait loci (QTL).


METHODS
A set of 1094 single selected Caucasian ADHD nuclear families was genotyped on a highly accurate and informative single nucleotide polymorphism (SNP) panel. Two quantitative traits measuring the children's symptoms in home and school settings were collected and standardized according to a population sample of 8000 children to reflect the developmental nature and gender prevalence difference of ADHD. Univariate linkage test was performed on both traits and their mean score.


RESULTS
A significant common linkage locus was found at chromosome 1p36 with a locus-specific heritability of 5.1% and a genomewide empirical p < .04. Setting-specific suggestive linkage signals were also found: logarithm of odds (LOD) = 2.2 at 9p23 for home trait and LOD = 2.6 at 11q21 for school trait.


CONCLUSIONS
These results indicate that given large samples with proper phenotypic measures, searching for ADHD genes with a QTL strategy is an important alternative to using the clinical diagnosis. The fact that our linkage region 1p36 overlaps with the dyslexia QTL DYX8 further suggests it is potentially a pleiotropic locus for ADHD and dyslexia.
Zhou
Kaixin
K
MRC Social Genetic Developmental and Psychiatry Centre, King's College London, London, UK.
Asherson
Philip
P
Sham
Pak
P
Franke
Barbara
B
Anney
Richard J L
RJ
Buitelaar
Jan
J
Ebstein
Richard
R
Gill
Michael
M
Brookes
Keeley
K
Buschgens
Cathelijne
C
Campbell
Desmond
D
Chen
Wai
W
Christiansen
Hanna
H
Fliers
Ellen
E
Gabriëls
Isabel
I
Johansson
Lena
L
Marco
Rafaela
R
Mulas
Fernando
F
Müller
Ueli
U
Mulligan
Aisling
A
Neale
Benjamin M
BM
Rijsdijk
Fruhling
F
Rommelse
Nanda
N
Uebel
Henrik
H
Psychogiou
Lamprini
L
Xu
Xiaohui
X
Banaschewski
Tobias
T
Sonuga-Barke
Edmund
E
Eisenberg
Jacques
J
Manor
Iris
I
Miranda
Ana
A
Oades
Robert D
RD
Roeyers
Herbert
H
Rothenberger
Aribert
A
Sergeant
Joseph
J
Steinhausen
Hans-Christoph
HC
Taylor
Eric
E
Thompson
Margaret
M
Faraone
Stephen V
SV
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D004410:Dyslexia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D008297:Male; D010641:Phenotype; D012574:Schools; D012931:Social Environment; D044465:White People / Q000235:genetics