Case-control genome-wide association study of attention-deficit/hyperactivity disorder.
OBJECTIVE
Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. Thus additional genomewide association studies (GWAS) are needed.


METHODS
We used case-control analyses of 896 cases with DSM-IV ADHD genotyped using the Affymetrix 5.0 array and 2,455 repository controls screened for psychotic and bipolar symptoms genotyped using Affymetrix 6.0 arrays. A consensus SNP set was imputed using BEAGLE 3.0, resulting in an analysis dataset of 1,033,244 SNPs. Data were analyzed using a generalized linear model.


RESULTS
No genome-wide significant associations were found. The most significant results implicated the following genes: PRKG1, FLNC, TCERG1L, PPM1H, NXPH1, PPM1H, CDH13, HK1, and HKDC1.


CONCLUSIONS
The current analyses are a useful addition to the present literature and will make a valuable contribution to future meta-analyses. The candidate gene findings are consistent with a prior meta-analysis in suggesting that the effects of ADHD risk variants must, individually, be very small and/or include multiple rare alleles.
Neale
Benjamin M
BM
Center for Human Genetic Research, Massachusettes General Hospital, Boston, MA, USA.
Medland
Sarah
S
Ripke
Stephan
S
Anney
Richard J L
RJ
Asherson
Philip
P
Buitelaar
Jan
J
Franke
Barbara
B
Gill
Michael
M
Kent
Lindsey
L
Holmans
Peter
P
Middleton
Frank
F
Thapar
Anita
A
Lesch
Klaus-Peter
KP
Faraone
Stephen V
SV
Daly
Mark
M
Nguyen
Thuy Trang
TT
Schäfer
Helmut
H
Steinhausen
Hans-Christoph
HC
Reif
Andreas
A
Renner
Tobias J
TJ
Romanos
Marcel
M
Romanos
Jasmin
J
Warnke
Andreas
A
Walitza
Susanne
S
Freitag
Christine
C
Meyer
Jobst
J
Palmason
Haukur
H
Rothenberger
Aribert
A
Hawi
Ziarih
Z
Sergeant
Joseph
J
Roeyers
Herbert
H
Mick
Eric
E
Biederman
Joseph
J
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D016022:Case-Control Studies; D002648:Child; D015897:Comorbidity; D004200:Diseases in Twins / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics