Common genetic variation and performance on standardized cognitive tests
Common genetic variation and performance on standardized cognitive tests
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DOI：
10.1038/ejhg.2010.2
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发表时间：
2010-07-01
影响因子：
5.2
通讯作者：
Goldstein, David B.
中科院分区：
文献类型：
--
作者：
Cirulli, Elizabeth T.;Kasperaviciute, Dalia;Goldstein, David B.
最近完成的一系列全基因组关联研究的一个令人惊讶的特征是，可单独检测的多态性中的常见遗传变异对许多人类特征的影响有限。这对于精神疾病的研究尤其明显，这些研究未能对常见变异产生清晰、可复制的关联。对这些负面结果的一种流行解释是，其中许多性状可能具有遗传异质性，从而导致相关内表型可能在遗传上更容易处理。认知方面可能是精神分裂症等精神疾病最重要的内表型，这导致许多研究人员对正常人群认知表现的遗传因素进行大规模研究，作为疾病易感性方面的替代。在这里，我们对 1086 名健康志愿者进行了一项全基因组关联研究，对执行功能（数字符号和斯特鲁普颜色词）进行了两项测试，并对其中 514 名志愿者进行了扩展的认知电池测试。我们表明，与已发表的关于精神疾病本身的研究一致，没有任何一种常见变异对健康个体在标准化认知测试中的表现有很大影响（解释>4-8%的群体变异）。鉴于这些是重要的内表型，我们的工作与这样的观点是一致的：识别精神疾病的罕见遗传原因对于未来的研究可能比识别遗传同质的内表型更重要。欧洲人类遗传学杂志 (2010) 18, 815-820; doi：10.1038/ejhg.2010.2； 2010 年 2 月 3 日在线发布
One surprising feature of the recently completed waves of genome-wide association studies is the limited impact of common genetic variation in individually detectable polymorphisms on many human traits. This has been particularly pronounced for studies on psychiatric conditions, which have failed to produce clear, replicable associations for common variants. One popular explanation for these negative findings is that many of these traits may be genetically heterogeneous, leading to the idea that relevant endophenotypes may be more genetically tractable. Aspects of cognition may be the most important endophenotypes for psychiatric conditions such as schizophrenia, leading many researchers to pursue large-scale studies on the genetic contributors of cognitive performance in the normal population as a surrogate for aspects of liability to disease. Here, we perform a genome-wide association study with two tests of executive function, Digit Symbol and Stroop Color-Word, in 1086 healthy volunteers and with an expanded cognitive battery in 514 of these volunteers. We show that, consistent with published studies of the psychiatric conditions themselves, no single common variant has a large effect (explaining >4-8% of the population variation) on the performance of healthy individuals on standardized cognitive tests. Given that these are important endophenotypes, our work is consistent with the idea that identifying rare genetic causes of psychiatric conditions may be more important for future research than identifying genetically homogenous endophenotypes. European Journal of Human Genetics (2010) 18, 815-820; doi: 10.1038/ejhg.2010.2; published online 3 February 2010