Attention deficit hyperactivity disorder (ADHD) and the dopamine D4 receptor gene: evidence of association but no linkage in a UK sample

Citation
J. Mill et al., Attention deficit hyperactivity disorder (ADHD) and the dopamine D4 receptor gene: evidence of association but no linkage in a UK sample, MOL PSYCHI, 6(4), 2001, pp. 440-444
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
MOLECULAR PSYCHIATRY
ISSN journal
1359-4184 → ACNP
Volume
6
Issue
4
Year of publication
2001
Pages
440 - 444
Database
ISI
SICI code
1359-4184(200107)6:4<440:ADHD(A>2.0.ZU;2-L
Abstract
Recent studies report association and linkage between attention deficit hyp eractivity disorder (ADHD) and the 7-repeat allele of a 48 base-pair repeat in the dopamine D4 receptor gene (DRD4).(1) We examined the frequency of t his allele in a sample of probands with DSM-IV ADHD using a case-control de sign, as well as the transmission disequilibrium test (TDT) and haplotype-b ased haplotype relative risk (HHRR) in the subset of probands with DNA avai lable from both parents. One hundred and thirty-two ADHD probands were comp ared 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 o ne 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 prob ands using TRANSMIT(2) provided no additional evidence for excess transmiss ion of the 7-repeat allele (58 transmitted vs 54 non-transmitted). HHRR gav e 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-en vironment correlation.