Characterizing the Genetic Overlap Between Psychiatric Disorders and Sleep-Related Phenotypes

Biol Psychiatry. 2021 Nov 1;90(9):621-631. doi: 10.1016/j.biopsych.2021.07.007. Epub 2021 Jul 14.


Background: A range of sleep disturbances are commonly experienced by patients with psychiatric disorders, and genome-wide genetic analyses have shown some significant genetic correlations between these traits. Here, we applied novel statistical genetic methodologies to better characterize the potential shared genetic architecture between sleep-related phenotypes and psychiatric disorders.

Methods: Using the MiXeR method, which can estimate polygenic overlap beyond genetic correlation, the shared genetic architecture between major psychiatric disorders (bipolar disorder [N = 51,710], depression [N = 480,359], and schizophrenia [N = 77,096]) and sleep-related phenotypes (chronotype [N = 449,734], insomnia [N = 386,533] and sleep duration [N = 446,118]) were quantified on the basis of genetic summary statistics. Furthermore, the conditional/conjunctional false discovery rate framework was used to identify specific shared loci between these phenotypes, for which positional and functional annotation were conducted with FUMA.

Results: Extensive genetic overlap between the sleep-related phenotypes and bipolar disorder (63%-77%), depression (76%-79%), and schizophrenia (64%-79%) was identified, with moderate levels of congruence between most investigated traits (47%-58%). Specific shared loci were identified for all bivariate analyses, and a subset of 70 credible genes were mapped to these shared loci.

Conclusions: The current results provide evidence for substantial polygenic overlap between psychiatric disorders and sleep-related phenotypes, beyond genetic correlation (|rg| = 0.02 to 0.42). Moderate congruency within the shared genetic components suggests a complex genetic relationship and potential subgroups with higher or lower genetic concordance. This work provides new insights and understanding of the shared genetic etiology of sleep-related phenotypes and psychiatric disorders and highlights new opportunities and avenues for future investigation.

Keywords: Genetic overlap; Mental health; Pleiotropy; Psychiatric disorder; Sleep.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Mental Disorders* / genetics
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Sleep / genetics