Abstract
Insomnia and restless leg syndrome (RLS) are associated with increased risk for suicidal behavior (SB), which is often comorbid with mood or thought disorders; however, it is unclear whether these relationships are causal. We performed a two-sample Mendelian randomization study using summary-level genetic associations with insomnia symptoms and RLS against the outcomes of risk of major depressive disorder (MDD), bipolar disorder (BP), schizophrenia (SCZ), and SB. The inverse-variance weighted method was used in the main analysis. We performed replication and sensitivity analyses to examine the robustness of the results. We identified outcome cohorts for MDD (n = 170,756 cases/329,443 controls), BP (n = 20,352/31,358), SCZ (n = 69,369/236,642), SB-Cohort-2019 (n = 6569/14,996 all with MDD, BP or SCZ; and SB within individual disease categories), and SB-Cohort-2020 (n = 29,782/519,961). Genetically proxied liability to insomnia symptoms significantly associated with increased risk of MDD (odds ratio (OR) = 1.23, 95% confidence interval (CI) = 1.2–1.26, P = 1.37 × 10–61), BP (OR = 1.15, 95% CI = 1.07–1.23, P = 5.11 × 10–5), SB-Cohort-2019 (OR = 1.17, 95% CI = 1.07–1.27, P = 2.30 × 10–4), SB-Cohort-2019 in depressed patients (OR = 1.34, 95% CI = 1.16–1.54, P = 5.97 × 10–5), and SB-Cohort-2020 (OR = 1.24, 95% CI = 1.18–1.3, P = 1.47 × 10–18). Genetically proxied liability to RLS did not significantly influence the risk of any of the outcomes (all corrected P > 0.05). Results were replicated for insomnia with MDD and SB in Mass General Brigham Biobank and were consistent in multiple lines of sensitivity analyses. In conclusion, human genetic evidence supports for the first time a potentially independent and causal effect of insomnia on SB and encourages further clinical investigation of treatment of insomnia for prevention or treatment of SB.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1672-1679 |
| Number of pages | 8 |
| Journal | Neuropsychopharmacology |
| Volume | 47 |
| Issue number | 9 |
| DOIs | |
| State | Published - Aug 2022 |
Funding
RS and JW are partially supported by NIH grant R01HL146751. We thank the GWAS consortia that have made their data publicly available. We thank the International Suicide Genetics Consortium that shared its summary statistics with us. None of the individual authors have conflict of interest to disclose. International Suicide Genetics Consortium disclosures for their GWAS of suicidal behavior: statistical analyses were carried out on the NL Genetic Cluster Computer ( http://www.geneticcluster.org ) hosted by SURFsara and the Mount Sinai high performance computing cluster ( http://hpc.mssm.edu ), which is supported by the Office of Research Infrastructure of the National Institutes of Health under award numbers S10OD018522 and S10OD026880. This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work is supported by R01MH116269 (DMR) and R01MH121455 (DMR). Research reported was also supported by NIGMS of the National Institutes of Health under award number T32GM007347 (JK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
ASJC Scopus subject areas
- Psychiatry and Mental health
- Pharmacology