Norton Nadine, Williams Hywel J, Owen Michael J
Department of Psychological Medicine, Wales School of Medicine, Cardiff University, Heath Park, Cardiff, UK.
Curr Opin Psychiatry. 2006 Mar;19(2):158-64. doi: 10.1097/01.yco.0000214341.52249.59.
This paper reviews recent molecular genetic studies of schizophrenia and evaluates claims implicating specific genes as susceptibility loci.
Molecular genetic studies have identified several potential regions of linkage and two associated chromosomal abnormalities, and the evidence is accumulating in favour of several positional candidate genes. Currently, the strongest evidence for putative schizophrenia susceptibility loci relates to the genes encoding dysbindin (DTNBP1) and neuregulin (NRG1). For other genes, disrupted in schizophrenia (DISC1), D-amino acid oxidase activator (DAOA), regulator of G-protein signalling 4 (RGS4) and V-AKT murine thymoma viral oncogene homolog 1 (AKT1) the data are promising but not yet compelling. In the most convincing cases, the risk haplotypes appear to be associated with small effect sizes and do not fully explain the linkage findings that prompted each study.
The ability of positional genetics to implicate novel genes and pathways will open up new vistas for neurobiological research. Despite the accumulation of significant genetic data, however, the susceptibility variants have yet to be identified and detailed follow-up studies are now required.
本文回顾了近期关于精神分裂症的分子遗传学研究，并评估了有关特定基因作为易感位点的说法。
分子遗传学研究已确定了几个潜在的连锁区域和两种相关的染色体异常，支持几个定位候选基因的证据也在不断积累。目前，关于假定的精神分裂症易感位点的最有力证据与编码失调素（DTNBP1）和神经调节蛋白（NRG1）的基因有关。对于其他基因，如精神分裂症相关基因（DISC1）、D-氨基酸氧化酶激活剂（DAOA）、G蛋白信号调节因子4（RGS4）和V-AKT小鼠胸腺瘤病毒癌基因同源物1（AKT1），数据很有前景，但尚不具有说服力。在最有说服力的案例中，风险单倍型似乎与较小的效应大小相关，并且不能完全解释促使每项研究的连锁研究结果。
定位遗传学识别新基因和新通路的能力将为神经生物学研究开辟新的前景。然而，尽管积累了大量的遗传数据，但尚未确定易感变异体现在需要进行详细的后续研究。
