Family-based genome-wide association scan of attention-deficit/hyperactivity disorder.
OBJECTIVE
Genes likely play a substantial role in the etiology of attention-deficit/hyperactivity disorder (ADHD). However, the genetic architecture of the disorder is unknown, and prior genome-wide association studies (GWAS) have not identified a genome-wide significant association. We have conducted a third, independent, multisite GWAS of DSM-IV-TR ADHD.


METHODS
Families were ascertained at Massachusetts General Hospital (MGH; N = 309 trios), Washington University at St. Louis (WASH-U; N = 272 trios), and University of California at Los Angeles (UCLA; N = 156 trios). Genotyping was conducted with the Illumina Human1M or Human1M-Duo BeadChip platforms. After applying quality control filters, association with ADHD was tested with 835,136 SNPs in 735 DSM-IV ADHD trios from 732 families.


RESULTS
Our smallest p value (6.7E-07) did not reach the threshold for genome-wide statistical significance (5.0E-08), but one of the 20 most significant associations was located in a candidate gene of interest for ADHD (SLC9A9, rs9810857, p = 6.4E-6). We also conducted gene-based tests of candidate genes identified in the literature and found additional evidence of association with SLC9A9.


CONCLUSIONS
We and our colleagues in the Psychiatric GWAS Consortium are working to pool together GWAS samples to establish the large data sets needed to follow-up on these results and to identify genes for ADHD and other disorders.
Mick
Eric
E
Massachusetts General Hospital, 55 Fruit Street-Warren 705, Boston, MA 02114, USA. emick1@partners.org
Todorov
Alexandre
A
Smalley
Susan
S
Hu
Xiaolan
X
Loo
Sandra
S
Todd
Richard D
RD
Biederman
Joseph
J
Byrne
Deirdre
D
Dechairo
Bryan
B
Guiney
Allan
A
McCracken
James
J
McGough
James
J
Nelson
Stanley F
SF
Reiersen
Angela M
AM
Wilens
Timothy E
TE
Wozniak
Janet
J
Neale
Benjamin M
BM
Faraone
Stephen V
SV
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D002648:Child; D002675:Child, Preschool; D039721:Diagnostic and Statistical Manual of Mental Disorders; 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; D010552:Personality Assessment; D020641:Polymorphism, Single Nucleotide / Q000235:genetics