Candidate gene analysis in an on-going genome-wide association study of attention-deficit hyperactivity disorder: suggestive association signals in ADRA1A.
OBJECTIVE
Attention-deficit hyperactivity disorder (ADHD) is a highly heritable, common developmental disorder. Although a few confirmed associations have emerged from candidate gene studies, these have shown the same limitations that have become evident in the study of other complex diseases, often with inconsistent and nonreplicated results across different studies.


METHODS
In this report, 27 ADHD candidate genes were explored in greater depth using high-density tag single nucleotide polymorphism (SNP) genotyping. Association with 557 SNPs was tested using the transmission disequilibrium test in 270 nuclear pedigrees selected from an ongoing ADHD genetic study that includes all disease subtypes.


RESULTS
SNPs in seven genes including SLC1A3, SLC6A3, HTR4, ADRA1A, HTR2A, SNAP25, and COMT showed a nominal level of association with ADHD (P values <0.05), but none remained significant after a stringent correction for the total number of tests performed.


CONCLUSIONS
The strongest signal emerged from SNPs in the promoter region (rs3808585) and in an intron (rs17426222, rs4732682, rs573514) of ADRA1A, all located within the same haplotype block. Some of the SNPs in HTR2A and COMT have already been reported by others, whereas other SNPs will need confirmation in independent samples.
Department of Pediatrics, Division of Pulmonary Medicine, Center for Applied Genomics, The University of Pennsylvania, Philadelphia, Pennsylvania, USA. elia@email.chop.edu
Josephine
J
Elia
Mario
M
Capasso
Zafar
Z
Zaheer
Francesca
F
Lantieri
Paul
P
Ambrosini
Wade
W
Berrettini
Marcella
M
Devoto
Hakon
H
Hakonarson
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002648:Child; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics*
C547713:ADRA1A protein, human; D018340:Receptors, Adrenergic, alpha-1