Genome-wide tandem repeat expansions contribute to schizophrenia risk

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.

Automated summary

This study found that adults with schizophrenia have a higher burden of rare tandem repeat expansions (TREs) near exons in their genomes compared with non-psychiatric controls. These TREs are disproportionately located at loci associated with schizophrenia from genome-wide association studies, present in individuals with clinically-relevant genetic variants at other schizophrenia loci, and found in families with multiple individuals affected by schizophrenia. The study also showed that these rare TREs may disrupt synaptic function by affecting the splicing process of their associated genes.