Canadian Institute of Health Research/Michael Smith Foundation for Health Research (CIHR/MSFHR) Graduate Program in Bioinformatics, University of British Columbia, BC, Canada.
Neuroscience. 2010 May 5;167(2):384-95. doi: 10.1016/j.neuroscience.2010.01.016. Epub 2010 Feb 4.
Expression profiling of post-mortem human brain tissue has been widely used to study molecular changes associated with neuropsychiatric diseases as well as normal processes such as aging. Changes in expression associated with factors such as age, gender or postmortem interval are often more pronounced than changes associated with disease. Therefore in addition to being of interest in their own right, careful consideration of these effects are important in the interpretation of disease studies. We performed a large meta-analysis of genome-wide expression studies of normal human cortex to more fully catalogue the effects of age, gender, postmortem interval and brain pH, yielding a "meta-signature" of gene expression changes for each factor. We validated our results by showing a significant overlap with independent gene lists extracted from the literature. Importantly, meta-analysis identifies genes which are not significant in any individual study. Finally, we show that many schizophrenia candidate genes appear in the meta-signatures, reinforcing the idea that studies must be carefully controlled for interactions between these factors and disease. In addition to the inherent value of the meta-signatures, our results provide critical information for future studies of disease effects in the human brain.
对人死后脑组织的表达谱进行分析已广泛用于研究与神经精神疾病相关的分子变化，以及衰老等正常过程。与年龄、性别或死后间隔等因素相关的表达变化通常比与疾病相关的变化更为明显。因此，除了本身就很有意义之外，在解释疾病研究时，仔细考虑这些影响也很重要。我们对正常人类大脑皮层的全基因组表达研究进行了大规模的荟萃分析，以更全面地描述年龄、性别、死后间隔和大脑 pH 值的影响，为每个因素生成一个基因表达变化的“荟萃签名”。我们通过显示与从文献中提取的独立基因列表有显著重叠来验证我们的结果。重要的是，荟萃分析确定了在任何单个研究中都不显著的基因。最后，我们发现许多精神分裂症候选基因出现在荟萃签名中，这强化了这样一种观点，即研究必须仔细控制这些因素与疾病之间的相互作用。除了荟萃签名的内在价值外，我们的研究结果还为未来人类大脑疾病效应的研究提供了关键信息。
