McDonald Colm, Murphy Kieran C
Division of Psychological Medicine, Institute of Psychiatry, de Crespigny Park, London SE5 8AF, United Kingdom.
Psychiatr Clin North Am. 2003 Mar;26(1):41-63. doi: 10.1016/s0193-953x(02)00030-8.
Despite the genetic and phenotypic complexity of schizophrenia, much progress has been made. Research has largely excluded the possibility that genes of major effect exist; linkage analysis has provided independently replicated evidence for genes of moderate effect on several chromosomal regions. Association studies suggest that alleles of at least two genes, those encoding D3 and 5HT2A, confer a small rise in susceptibility to schizophrenia, and there are convergent findings from several different lines of research implicating regions such as 22q11, although no specific causative genes for schizophrenia have been definitively identified yet. There are strong grounds for optimism as larger samples are collected to increase the power of studies, and novel methods of statistical analysis and large-scale genotyping of SNPs are developed and refined. Although the difficulties and challenges of genetics research into schizophrenia are formidable, the devastating personal and social consequences of the illness make it imperative that these challenges are faced, because the identification of susceptibility genes for schizophrenia would result in further productive neurobiologic research and ultimately improvements in the prevention and treatment of schizophrenia.
尽管精神分裂症在遗传和表型上具有复杂性，但已经取得了很大进展。研究在很大程度上排除了存在主要效应基因的可能性；连锁分析已经为几个染色体区域上具有中等效应的基因提供了独立重复的证据。关联研究表明，至少两个基因的等位基因，即编码D3和5HT2A的基因，会使精神分裂症易感性略有上升，并且来自几个不同研究方向的研究结果都指向了如22q11等区域，尽管尚未明确鉴定出精神分裂症的具体致病基因。随着收集更大样本以提高研究效力，以及开发和完善统计分析新方法和单核苷酸多态性（SNP）的大规模基因分型，我们有充分的理由保持乐观。尽管精神分裂症遗传学研究的困难和挑战巨大，但该疾病给个人和社会带来的毁灭性后果使得必须直面这些挑战，因为鉴定出精神分裂症的易感基因将推动进一步富有成效的神经生物学研究，并最终改善精神分裂症的预防和治疗。
