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

J Mill, S Curran, Lindsey Kent, S Richards, A Gould, V Virdee, L Huckett, J Sharp, C Batten, S Fernando, E Simanoff, M Thompson, J Zhao, P Sham, E Taylor, P Asherson

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73 Citations (Scopus)

Abstract

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).(1) 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(2) 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.

Original languageEnglish
Pages (from-to)440-444
Number of pages5
JournalMolecular Psychiatry
Volume6
Issue number4
Publication statusPublished - Jul 2001

Keywords

  • ADHD
  • DRD4
  • genetic association
  • III REPEAT POLYMORPHISM
  • DRD4 GENE
  • VARIANTS
  • QUESTIONNAIRE
  • CHILD

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