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

Mill, J., Curran, S., Kent, L., Richard, S., Gould, A., Virdee, V., Hucket, L., Sharp, J., Batten, C., Fernando, S., Simanoff, E., Thompson, M., Zhoa, J., Sham, P., Taylor, E. and Asherson, P. (2001) Attention deficit hyperactivity disorder (ADHD) and the dopamine D4 receptor gene: evidence of association but no linkage in a UK sample. Molecular Psychiatry, 6 (4), 440-444.

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 (chi2 = 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, chi2 = 0.69). Analysis of the entire sample of 132 probands using TRANSMIT2 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.

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