Coelewij Leda, Curtis David
UCL Genetics Institute, University College London, UK.
Centre for Psychiatry, Barts and the London School of Medicine and Dentistry, London, UK.
Ann Hum Genet. 2018 Sep;82(5):239-243. doi: 10.1111/ahg.12259. Epub 2018 Jun 20.
A number of important findings have recently emerged relevant to identifying genetic risk factors for schizophrenia. Findings using common variants point towards gene sets of interest and also demonstrate an overlap with other psychiatric and nonpsychiatric disorders. Imputation of variants of the gene for complement component 4 (C4) from GWAS data has shown that the predicted expression of the C4A product is associated with schizophrenia risk. Very rare variants disrupting SETD1A, RBM12 or NRXN1 have a large effect on risk. Other rare, damaging variants are enriched in genes that are loss of function intolerant and/or whose products localise to the synapse. These and particular copy number variants can result in increased risk of schizophrenia but also of other neurodevelopmental disorders. The findings for C4 and NRXN1 may be especially helpful for elucidating the biological mechanisms that can lead to disease.
最近出现了一些与确定精神分裂症遗传风险因素相关的重要发现。使用常见变异的研究结果指向了感兴趣的基因集，并且还表明与其他精神疾病和非精神疾病存在重叠。从全基因组关联研究（GWAS）数据中对补体成分4（C4）基因的变异进行推断表明，C4A产物的预测表达与精神分裂症风险相关。破坏SETD1A、RBM12或NRXN1的非常罕见的变异对风险有很大影响。其他罕见的、有害的变异在功能丧失不耐受和/或其产物定位于突触的基因中富集。这些以及特定的拷贝数变异可导致精神分裂症风险增加，也会导致其他神经发育障碍风险增加。C4和NRXN1的研究结果可能对阐明导致疾病的生物学机制特别有帮助。
