Owen M J, Craddock N, O'Donovan M C
Department of Psychological Medicine, Wales College of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK.
Trends Genet. 2005 Sep;21(9):518-25. doi: 10.1016/j.tig.2005.06.011.
Genetic epidemiological studies suggest that individual variation in susceptibility to schizophrenia is largely genetic, reflecting alleles of moderate to small effect in multiple genes. Molecular genetic studies have identified several potential regions of linkage and two associated chromosomal abnormalities, and evidence is accumulating in favour of several positional candidate genes. Currently, the positional candidate genes for which we consider the evidence to be strong are those encoding dysbindin (DTNBP1) and neuregulin 1 (NRG1). For other genes, disrupted in schizophrenia 1 (DISC1), D-amino-acid oxidase (DAO), D-amino-acid oxidase activator (DAOA, formerly known as G72) and regulator of G-protein signalling 4 (RGS4), the data are promising but not yet compelling. The identification of these, and other susceptibility genes, will open up new avenues for research aimed at understanding the pathogenesis of schizophrenia, and will catalyse a re-appraisal of the classification of psychiatric disorders.
遗传流行病学研究表明，个体对精神分裂症易感性的差异很大程度上是由基因决定的，这反映了多个基因中效应大小适中或较小的等位基因。分子遗传学研究已经确定了几个潜在的连锁区域和两种相关的染色体异常，并且越来越多的证据支持几个定位候选基因。目前，我们认为证据确凿的定位候选基因是那些编码失调素（DTNBP1）和神经调节蛋白1（NRG1）的基因。对于其他基因，如精神分裂症相关断裂基因1（DISC1）、D-氨基酸氧化酶（DAO）、D-氨基酸氧化酶激活剂（DAOA，原名G72）和G蛋白信号调节因子4（RGS4），数据很有前景，但尚不具有说服力。这些以及其他易感基因的鉴定，将为旨在理解精神分裂症发病机制的研究开辟新途径，并将促使人们重新评估精神疾病的分类。
