MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK.
Br Med Bull. 2009;91:61-74. doi: 10.1093/bmb/ldp017. Epub 2009 May 14.
Schizophrenia is a debilitating psychiatric disorder that imposes a considerable burden on sufferers, their families and society. The prominent involvement of genes, combined with the complexity and relative inaccessibility of the brain has led many to suggest that the identification of specific risk loci offers the best chance of understanding pathogenesis.
Recent genome-wide association studies (GWAS) and copy number variation (CNV) publications have been included in this review along with key papers from the fields of schizophrenia, functional psychoses and complex disease mapping.
Recent GWAS have now shown that both common alleles of small effect and rare alleles of moderate to large effect contribute to the high heritability of schizophrenia.
It is well known that many schizophrenic patients suffer symptoms seen in patients with bipolar disease and vice versa. There is now considerable interest in using aetiologically relevant risk factors, including genes, to explore the validity of the contemporary system of classification.
Rare CNVs have been shown to play a role in at least some cases of schizophrenia and it is highly predictable that this figure will rise with the use of technologies with higher resolution or that are better designed to assay common CNVs reliably.
The findings with common alleles thus far point to overlap in the genetic risk for schizophrenia and bipolar disorder, while the specific CNVs implicated in schizophrenia also increase susceptibility to a range of developmental disorders, including autism, mental retardation, attention deficit-hyperactivity disorder (ADHD) and epilepsy.
精神分裂症是一种使人衰弱的精神疾病，给患者、他们的家庭和社会带来了相当大的负担。基因的显著参与，加上大脑的复杂性和相对难以接近，导致许多人认为，确定特定的风险基因座最有机会了解发病机制。
本综述纳入了最近的全基因组关联研究（GWAS）和拷贝数变异（CNV）出版物，以及精神分裂症、功能性精神病和复杂疾病图谱领域的重要论文。
最近的 GWAS 表明，常见的小效应等位基因和罕见的中到大效应等位基因都对精神分裂症的高遗传性有贡献。
众所周知，许多精神分裂症患者都有双相情感障碍患者的症状，反之亦然。现在人们非常感兴趣的是，使用病因相关的风险因素，包括基因，来探索当代分类系统的有效性。
已经表明，罕见的 CNV 在至少一些精神分裂症病例中起作用，随着使用分辨率更高或更能可靠检测常见 CNV 的技术，这一数字将会上升，这是可以预见的。
到目前为止，常见等位基因的发现表明，精神分裂症和双相情感障碍的遗传风险存在重叠，而与精神分裂症有关的特定 CNV 也增加了一系列发育障碍的易感性，包括自闭症、智力迟钝、注意力缺陷多动障碍（ADHD）和癫痫。
