Parent of origin effects in attention/deficit hyperactivity disorder (ADHD): analysis of data from the international multicenter ADHD genetics (IMAGE) program.
There are conflicting reports suggesting that the parental origin of transmitted risk alleles may play a role in the etiology of attention deficit/hyperactivity disorder (ADHD). A recent report by Hawi and colleagues observed a generalized paternal over-transmission of alleles associated with ADHD. This was not replicated in more recent studies. Using data from a large multicenter study we examined the overall and gene-specific parent of origin effect in 554 independent SNPs across 47 genes. Transmission disequilibrium and explicit parent of origin test were performed using PLINK. Overall parent of origin effect was tested by Chi-square. There was no overall parent of origin effect in the IMAGE sample (chi(1)(2) = 1.82, P = 0.117). Five markers in three genes, DDC, TPH2, and SLC6A2 showed nominal association (P < 0.01) with ADHD combined subtype when restricted to maternal or paternal transmission only. Following the initial report by Hawi and co-workers three studies, including this one, found no evidence to support an overall parent of origin effect for markers associated with ADHD. We cannot however, exclude gene-specific parent of origin effect in the etiology ADHD.
Anney
Richard J L
RJ
Department of Psychiatry, Trinity College Dublin, St. James's Hospital, Dublin, Ireland. anneyr@tcd.ie
Hawi
Ziarih
Z
Sheehan
Karen
K
Mulligan
Aisling
A
Pinto
Carlos
C
Brookes
Keeley J
KJ
Xu
Xiaohui
X
Zhou
Kaixin
K
Franke
Barbara
B
Buitelaar
Jan
J
Vermeulen
Sita H
SH
Banaschewski
Tobias
T
Sonuga-Barke
Edmund
E
Ebstein
Richard
R
Manor
Iris
I
Miranda
Ana
A
Mulas
Fernando
F
Oades
Robert D
RD
Roeyers
Herbert
H
Rommelse
Nanda
N
Rothenberger
Aribert
A
Sergeant
Joseph
J
Steinhausen
Hans-Christoph
HC
Taylor
Eric
E
Thompson
Margaret
M
Asherson
Philip
P
Faraone
Stephen V
SV
Gill
Michael
M
D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology / Q000235:genetics*; D016009:Chi-Square Distribution; D003627:Data Interpretation, Statistical; D005190:Family; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D010290:Parents; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D005819:Genetic Markers