Barnett Jennifer H, Scoriels Linda, Munafò Marcus R
Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
Biol Psychiatry. 2008 Jul 15;64(2):137-44. doi: 10.1016/j.biopsych.2008.01.005. Epub 2008 Mar 14.
Cognitive endophenotypes may further our understanding of the genetic basis of psychiatric disorders, and the catechol-O-methyltransferase (COMT) gene is a promising candidate gene for both cognitive function and disorder. We conducted a meta-analysis of reported associations between the COMT Val158/108Met polymorphism and measures of memory and executive function.
The PubMed database was searched for studies relating cognitive functions and the COMT Val158/108Met polymorphism. This enabled meta-analyses of six cognitive phenotypes (Trail Making task, verbal recall, verbal fluency, IQ score, n-back task, and Wisconsin Card Sorting Test). Data were extracted by two reviewers and included cognitive scores by COMT genotype, publication year, diagnostic status, ancestry, proportion of male participants, and whether genotype frequencies were consistent with Hardy-Weinberg equilibrium.
We found no association between COMT genotype and the majority of phenotypes. There was evidence of association with IQ score (d = .06), which did not differ significantly by ancestry, sex, average sample age, or patient status. For the n-back task, there was no robust evidence for genetic association, but the effect size was significantly larger in patient (d = .40) than nonpatient (d = -.27) populations, larger in both samples with fewer male subjects, and those of greater average age. There was also evidence of publication bias and decreasing effect sizes with later publication.
Despite initially promising results, the COMT Val158/108Met polymorphism appears to have little if any association with cognitive function. Publication bias may hamper attempts to understand the genetic basis of psychological functions and psychiatric disorders.
认知内表型可能会加深我们对精神疾病遗传基础的理解，儿茶酚-O-甲基转移酶（COMT）基因是认知功能和疾病的一个很有前景的候选基因。我们对已报道的COMT Val158/108Met多态性与记忆及执行功能测量指标之间的关联进行了荟萃分析。
在PubMed数据库中搜索有关认知功能与COMT Val158/108Met多态性的研究。这使得能够对六种认知表型（连线测验、言语回忆、言语流畅性、智商分数、n-back任务和威斯康星卡片分类测验）进行荟萃分析。数据由两名审阅者提取，包括按COMT基因型分类的认知分数、发表年份、诊断状态、血统、男性参与者比例以及基因型频率是否符合哈迪-温伯格平衡。
我们发现COMT基因型与大多数表型之间无关联。有证据表明与智商分数存在关联（d = 0.06），且在血统、性别、平均样本年龄或患者状态方面无显著差异。对于n-back任务，没有确凿的遗传关联证据，但患者群体中的效应量（d = 0.40）显著大于非患者群体（d = -0.27），在男性受试者较少且平均年龄较大的两个样本中效应量也更大。也有证据表明存在发表偏倚，且随着发表时间的推移效应量减小。
尽管最初结果很有前景，但COMT Val158/108Met多态性似乎与认知功能几乎没有关联（如果有也是微乎其微）。发表偏倚可能会妨碍我们理解心理功能和精神疾病遗传基础的努力。
