Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
Mol Psychiatry. 2022 Sep;27(9):3692-3698. doi: 10.1038/s41380-022-01575-x. Epub 2022 May 12.
Tandem repeat expansions (TREs) can cause neurological diseases but their impact in schizophrenia is unclear. Here we analyzed genome sequences of adults with schizophrenia and found that they have a higher burden of TREs that are near exons and rare in the general population, compared with non-psychiatric controls. These TREs are disproportionately found at loci known to be associated with schizophrenia from genome-wide association studies, in individuals with clinically-relevant genetic variants at other schizophrenia loci, and in families where multiple individuals have schizophrenia. We showed that rare TREs in schizophrenia may impact synaptic functions by disrupting the splicing process of their associated genes in a loss-of-function manner. Our findings support the involvement of genome-wide rare TREs in the polygenic nature of schizophrenia.
串联重复扩展（TREs）可导致神经疾病，但它们在精神分裂症中的影响尚不清楚。在这里，我们分析了精神分裂症患者的基因组序列，发现与非精神疾病对照组相比，他们的 TRE 负担更高，这些 TRE 靠近外显子且在一般人群中罕见。这些 TRE 不成比例地存在于全基因组关联研究中与精神分裂症相关的已知基因座，在其他精神分裂症基因座具有临床相关遗传变异的个体中，以及在多个个体患有精神分裂症的家族中。我们表明，精神分裂症中的罕见 TRE 可能通过以功能丧失的方式破坏其相关基因的剪接过程来影响突触功能。我们的研究结果支持全基因组罕见 TRE 参与精神分裂症的多基因性质。
