Mill, J., Curran, S., Kent, L., Richards, 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 defecit hyperactive disorder (AD/HD) and the dopamine D4 receptor gene: evidence of association but no linkage in a UK sample. Molecular Psychiatry, 6 (4), 440-444. (doi:10.1038/sj.mp.4000881).
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 (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, 2 = 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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