Mill J, Curran S, Kent L, Richards S, Gould A, Virdee V, Huckett L, Sharp J, Batten C, Fernando S, Simanoff E, Thompson M, Zhao J, Sham P, Taylor E, Asherson P
Social, Genetic, and Development Psychiatry Research Centre, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
Mol Psychiatry. 2001 Jul;6(4):440-4. doi: 10.1038/sj.mp.4000881.
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.
近期研究报告了注意力缺陷多动障碍（ADHD）与多巴胺D4受体基因（DRD4）中一个48碱基对重复序列的7重复等位基因之间的关联和连锁关系。我们采用病例对照设计，研究了符合《精神疾病诊断与统计手册》第四版（DSM-IV）标准的ADHD先证者样本中该等位基因的频率，同时对那些可获取双亲DNA的先证者子集进行了传递不平衡检验（TDT）和基于单倍型的单倍型相对风险分析（HHRR）。将132名ADHD先证者与189名对照进行比较（卡方检验χ² = 6.17，自由度为1，P = 0.01，优势比OR = 1.73，95%可信区间CI = 1.11 - 2.71）。共有85个完整三联体可用于家系内的关联和连锁检验。52名携带一份7重复拷贝的杂合子父母可用于TDT分析（29个传递，23个未传递，χ² = 0.69）。使用TRANSMIT对132名先证者的整个样本进行分析，未提供7重复等位基因过度传递的额外证据（58个传递，54个未传递）。HHRR得出了相似的结果。我们得出结论，病例对照研究结果可能因基因分层而出现假阳性。然而，我们不能排除统计功效低和基因-环境相关性的其他解释。
