Attention deficit hyperactivity disorder (ADHD) and the dopamine D4 receptor gene: evidence of association but no linkage in a UK sample.
Recent studies report association and linkage between attention deficit hyperactivity disorder (ADHD) and the 7-repeat allele of a 48 base-pair repeat in the dopamine D4 receptor gene (DRD4). We examined the frequency of this allele in a sample of probands with DSM-IV ADHD using a case-control design, as well as the transmission disequilibrium test (TDT) and haplotype-based haplotype relative risk (HHRR) in the subset of probands with DNA available from both parents. One hundred and thirty-two ADHD probands were compared with 189 controls (chi(2) = 6.17, 1 df, P = 0.01, OR = 1.73, 95% CI = 1.11--2.71). A total of 85 complete trios were available for within-family tests of association and linkage. Fifty-two heterozygous parents carrying one copy of the 7-repeat were informative for the TDT (29 transmitted vs 23 non-transmitted, chi(2) = 0.69). Analysis of the entire sample of 132 probands using TRANSMIT provided no additional evidence for excess transmission of the 7-repeat allele (58 transmitted vs 54 non-transmitted). HHRR gave similar results. We conclude that the case-control findings are likely to be falsely positive, resulting from genetic stratification. However we can not rule out alternative explanations of low statistical power and gene-environment correlation.
Mill
J
J
Social, Genetic, and Development Psychiatry Research Centre, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
Curran
S
S
Kent
L
L
Richards
S
S
Gould
A
A
Virdee
V
V
Huckett
L
L
Sharp
J
J
Batten
C
C
Fernando
S
S
Simanoff
E
E
Thompson
M
M
Zhao
J
J
Sham
P
P
Taylor
E
E
Asherson
P
P
D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000523:psychology; D016022:Case-Control Studies; D002648:Child; D005091:Exons; D005189:False Positive Reactions; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D018598:Minisatellite Repeats; D010290:Parents; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050638:Receptors, Dopamine D4; D015203:Reproducibility of Results; D012306:Risk; D012984:Software; D006113:United Kingdom; D044465:White People / Q000235:genetics
C493599:DRD4 protein, human; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4