Genome-wide association studies (GWASs) have revealed substantial genetic components comprised of single nucleotide polymorphisms (SNPs) in the heritable risk of psychiatric disorders. However, genetic risk factors not covered by GWAS also play pivotal roles in these illnesses. Tandem repeats, which are likely functional but frequently overlooked by GWAS, may account for an important proportion in the “missing heritability” of psychiatric disorders. Despite difficulties in characterizing and quantifying tandem repeats in the genome, studies have been carried out in an attempt to describe impact of tandem repeats on gene regulation and human phenotypes. In this review, we have introduced recent research progress regarding the genomic distribution and regulatory mechanisms of tandem repeats. We have also summarized the current knowledge of the genetic architecture and biological underpinnings of psychiatric disorders brought by studies of tandem repeats. These findings suggest that tandem repeats, in candidate psychiatric risk genes or in different levels of linkage disequilibrium (LD) with psychiatric GWAS SNPs and haplotypes, may modulate biological phenotypes related to psychiatric disorders (e.g., cognitive function and brain physiology) through regulating alternative splicing, promoter activity, enhancer activity and so on. In addition, many tandem repeats undergo tight natural selection in the human lineage, and likely exert crucial roles in human brain evolution. Taken together, the putative roles of tandem repeats in the pathogenesis of psychiatric disorders is strongly implicated, and using examples from previous literatures, we wish to call for further attention to tandem repeats in the post-GWAS era of psychiatric disorders.

全基因组关联研究 (GWAS) 揭示了精神疾病的遗传风险中由单核苷酸多态性 (SNP) 组成的大量遗传成分。然而，GWAS 未涵盖的遗传风险因素也在这些疾病中发挥着关键作用。可能具有功能但经常被 GWAS 忽视的串联重复序列可能在精神疾病的“遗传缺失”中占重要比例。尽管难以表征和量化基因组中的串联重复，但已经进行了研究以试图描述串联重复对基因调控和人类表型的影响。在这篇综述中，我们介绍了串联重复的基因组分布和调控机制的最新研究进展。我们还总结了串联重复研究带来的精神疾病的遗传结构和生物学基础的当前知识。这些发现表明，在候选精神病风险基因中或在与精神病 GWAS SNP 和单倍型不同水平的连锁不平衡 (LD) 中，串联重复可能通过调节可变剪接来调节与精神疾病相关的生物表型（例如，认知功能和脑生理学） 、启动子活性、增强子活性等。此外，许多串联重复在人类谱​​系中经历了严格的自然选择，并可能在人类大脑进化中发挥关键作用。综上所述，串联重复在精神疾病发病机制中的推定作用是密切相关的，并且使用以前文献中的例子，