Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, United States.
Schizophr Res. 2010 Nov;123(2-3):234-43. doi: 10.1016/j.schres.2010.08.022. Epub 2010 Sep 15.
The co-occurrence of schizophrenia (SCZ) and type 2 diabetes mellitus (T2D) has been well documented. This review article focuses on the hypothesis that the co-occurrence of SCZ and T2D may be, at least in part, driven by shared genetic factors. Previous genetic studies of T2D and SCZ evidence have disclosed a number of overlapped risk loci. However, the putative common genetic factors for SCZ and T2D remain inconclusive due to inconsistent findings. A systemic review of methods of identifying genetic loci contributing to the comorbidity link between SCZ and T2D is hence needed. In the current review article, we have discussed several different approaches to localizing the shared susceptibility genes for these two diseases. To begin with, one could start with probing the gene involved in both glucose and dopamine metabolisms. Additionally, hypothesis-free genome-wide association studies (GWAS) may provide more clues to the common genetic basis for these two diseases. Genetic similarities inferred from GWAS may shed some light on the genetic mechanism underlying the comorbidity link between SCZ and T2D. Meanwhile, endophenotypes (e.g., adiponectin level in T2D and working memory in SCZ) may serve as alternative phenotypes that are more directly influenced by genes than target diseases. Hence, endophenotypes of these diseases may be more tractable to identification. To summarize, novel approaches are needed to dissect the complex genetic basis of the comorbidity of SCZ and T2D.
精神分裂症（SCZ）和 2 型糖尿病（T2D）的共病现象已有充分记录。本文综述的重点是这样一种假设，即 SCZ 和 T2D 的共病可能至少部分是由共同的遗传因素驱动的。先前对 T2D 和 SCZ 证据的遗传研究揭示了许多重叠的风险位点。然而，由于研究结果不一致，SCZ 和 T2D 的潜在共同遗传因素仍不确定。因此，需要对识别 SCZ 和 T2D 共病关联中遗传位点的方法进行系统综述。在本文中，我们讨论了几种不同的方法来定位导致这两种疾病共病的共同易感基因。首先，可以从研究涉及葡萄糖和多巴胺代谢的基因开始。此外，无假设的全基因组关联研究（GWAS）可能为这两种疾病的共同遗传基础提供更多线索。从 GWAS 推断出的遗传相似性可能为 SCZ 和 T2D 共病的遗传机制提供一些启示。同时，表型（如 T2D 中的脂联素水平和 SCZ 中的工作记忆）可以作为替代表型，它们比目标疾病更直接受基因影响。因此，这些疾病的表型可能更容易识别。总之，需要新的方法来剖析 SCZ 和 T2D 共病的复杂遗传基础。
