Munafò M R, Bowes L, Clark T G, Flint J
Cancer Research UK GPRG, Department of Clinical Pharmacology, University of Oxford, Oxford, UK.
Mol Psychiatry. 2005 Aug;10(8):765-70. doi: 10.1038/sj.mp.4001664.
There is strong evidence for a genetic contribution to schizophrenia, but the contribution of individual candidate genes remains uncertain. We attempted to replicate a recent meta-analysis that reported an association of the catechol O-methyltransferase (COMT) Val allele with schizophrenia, and suggested that this effect may be moderated by ancestry. We included reports published subsequent to the original meta-analysis, and included a formal test of the moderating effect of ancestry in order to test whether the association operates differently in populations of European ancestry compared to populations of Asian ancestry. A corrected P-value for the 5% significance threshold was employed where appropriate, using Bonferroni's method, and studies that demonstrated departure from Hardy-Weinberg equilibrium among controls were excluded. When all studies were included in a meta-regression, there was evidence for a significant association of COMT Val allele frequency with schizophrenia case status and a significant main effect of ancestry. The interaction of COMT Val allele frequency and ancestry was also significant. However, when only studies that reported allele frequencies that did not depart significantly from Hardy-Weinberg equilibrium among controls were included, these effects were no longer significant. The results of our meta-analysis do not support an association between the COMT Val allele and schizophrenia case status, and do not support recent claims that this association may be moderated by ancestry.
有强有力的证据表明基因对精神分裂症有影响，但单个候选基因的作用仍不明确。我们试图重复最近一项荟萃分析，该分析报告了儿茶酚-O-甲基转移酶（COMT）缬氨酸等位基因与精神分裂症的关联，并表明这种效应可能受祖先血统的调节。我们纳入了原始荟萃分析之后发表的报告，并进行了一项关于祖先血统调节效应的正式检验，以测试该关联在欧洲血统人群和亚洲血统人群中是否有不同表现。在适当情况下，使用邦费罗尼方法采用5%显著性阈值的校正P值，并排除那些显示对照组偏离哈迪-温伯格平衡的研究。当所有研究纳入荟萃回归时，有证据表明COMT缬氨酸等位基因频率与精神分裂症病例状态存在显著关联，且祖先血统有显著的主效应。COMT缬氨酸等位基因频率与祖先血统的相互作用也很显著。然而，当仅纳入那些报告对照组等位基因频率未显著偏离哈迪-温伯格平衡的研究时，这些效应不再显著。我们的荟萃分析结果不支持COMT缬氨酸等位基因与精神分裂症病例状态之间的关联，也不支持最近关于这种关联可能受祖先血统调节的说法。
