Hattori E, Liu C, Zhu H, Gershon E S
Department of Psychiatry, The University of Chicago, Chicago, IL, USA.
Mol Psychiatry. 2005 Aug;10(8):719-40. doi: 10.1038/sj.mp.4001695.
To liberate candidate gene analyses from criticisms of inexhaustiveness of examination of specific candidate genes, or incompleteness in the choice of candidate genes to study for specific neurobiological pathways, study of sizeable sets of genes pertinent to each putative pathophysiological pathway is required. For many years, genes have been tested in a 'one by one' manner for association with major affective disorders, primarily bipolar illness. However, it is conceivable that not individual genes but abnormalities in several genes within a system or in several neuronal, neural, or hormonal systems are implicated in the functional hypotheses for etiology of affective disorders. Compilation of candidate genes for entire pathways is a challenge, but can reasonably be carried out for the major affective disorders as discussed here. We present here five groupings of genes implicated by neuropharmacological and other evidence, which suggest 252 candidate genes worth examining. Inexhaustiveness of gene interrogation would apply to many studies in which only one polymorphism per gene is analyzed. In contrast to whole-genome association studies, a study of a limited number of candidate genes can readily exploit information on genomic sequence variations obtained from databases and/or resequencing, and has an advantage of not having the complication of an extremely stringent statistical criterion for association.
为了使候选基因分析摆脱对特定候选基因检查不全面或特定神经生物学途径研究中候选基因选择不完整的批评，需要对与每个假定病理生理途径相关的大量基因集进行研究。多年来，基因一直以“逐个”方式进行测试，以确定其与主要情感障碍（主要是双相情感障碍）的关联。然而，可以想象，情感障碍病因的功能假说涉及的不是单个基因，而是一个系统内或几个神经元、神经或激素系统中的几个基因的异常。编制整个途径的候选基因是一项挑战，但对于本文讨论的主要情感障碍来说是可以合理进行的。我们在此展示了五组由神经药理学和其他证据表明的基因，这表明有252个候选基因值得研究。基因询问的不全面性将适用于许多仅分析每个基因一个多态性的研究。与全基因组关联研究相比，对有限数量候选基因的研究可以很容易地利用从数据库和/或重测序获得的基因组序列变异信息，并且具有不必面对极其严格的关联统计标准这一复杂问题的优势。
