Van Den Bogaert Ann, Del-Favero Jurgen, Van Broeckhoven Christine
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium.
Hum Mutat. 2006 Sep;27(9):833-53. doi: 10.1002/humu.20369.
Psychiatric disorders, including affective disorders (AD) and schizophrenia (SZ) are among the most common disabling brain diseases in Western populations and result in high costs in terms of morbidity as well as mortality. Although their etiology and pathophysiology is largely unknown, family-, twin-, and adoption studies argue for a strong genetic determination of these disorders. These studies indicate that there is between 40 and 85% heritability for these disorders but point also to the importance of environmental factors. Therefore, any research strategy aiming at the identification of genes involved in the development of AD and SZ should account for the complex nature (multifactorial) of these disorders. During the last decade, molecular genetic studies have contributed a great deal to the identification of genetic factors involved in complex disorders. Here we provide a comprehensive review of the most promising genes for AD and SZ, and the methods and approaches that were used for their identification. Also, we discuss the current knowledge and hypotheses that have been formulated regarding the effect of variations on protein functioning as well as recent observations that point to common molecular mechanisms.
精神疾病，包括情感障碍（AD）和精神分裂症（SZ），是西方人群中最常见的致残性脑部疾病，在发病率和死亡率方面造成了高昂的代价。尽管其病因和病理生理学在很大程度上尚不清楚，但家族、双胞胎和收养研究表明这些疾病具有很强的遗传决定性。这些研究表明，这些疾病的遗传度在40%至85%之间，但也指出了环境因素的重要性。因此，任何旨在识别参与AD和SZ发病的基因的研究策略都应考虑到这些疾病的复杂性质（多因素）。在过去十年中，分子遗传学研究为识别复杂疾病中的遗传因素做出了巨大贡献。在此，我们对AD和SZ最有前景的基因以及用于识别它们的方法和途径进行全面综述。此外，我们还讨论了目前关于变异对蛋白质功能影响的知识和假设，以及指向共同分子机制的最新观察结果。
