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

Kevin S O'Connell; Oleksandr Frei; Shahram Bahrami; Olav B Smeland; Francesco Bettella; Weiqiu Cheng; Yunhan Chu; Guy Hindley; Aihua Lin; Alexey Shadrin; Elizabeth Ann Barrett; Trine Vik Lagerberg; Nils Eiel Steen; Anders M Dale; Srdjan Djurovic; Ole A Andreassen

doi:10.1016/j.biopsych.2021.07.007

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.

Authors

Kevin S O'Connell¹, Oleksandr Frei², Shahram Bahrami², Olav B Smeland², Francesco Bettella², Weiqiu Cheng², Yunhan Chu², Guy Hindley³, Aihua Lin², Alexey Shadrin², Elizabeth Ann Barrett⁴, Trine Vik Lagerberg², Nils Eiel Steen², Anders M Dale⁵, Srdjan Djurovic⁶, Ole A Andreassen⁷

Affiliations

¹ NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, University of Oslo, Oslo, Norway. Electronic address: kevin.oconnell@medisin.uio.no.
² NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, University of Oslo, Oslo, Norway.
³ NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, University of Oslo, Oslo, Norway; Psychosis Studies, Institute of Psychiatry, Psychology and Neurosciences, King's College London, London, United Kingdom.
⁴ NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, University of Oslo, Oslo, Norway; Early Intervention in Psychosis Advisory Unit for South East Norway, Division of Mental Health and Addiction, Oslo University Hospital Trust, Oslo, Norway.
⁵ Department of Radiology, University of California San Diego, La Jolla, California; Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, California; Department of Psychiatry, University of California San Diego, La Jolla, California; Department of Neurosciences, University of California San Diego, La Jolla, California.
⁶ Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway.
⁷ NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, University of Oslo, Oslo, Norway. Electronic address: o.a.andreassen@medisin.uio.no.

PMID: 34482950
DOI: 10.1016/j.biopsych.2021.07.007

Abstract

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 (|r_g| = 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