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. 2024 Feb 8;47(2):zsad279.
doi: 10.1093/sleep/zsad279.

Genetics of sleep medication purchases suggests causality from sleep problems to psychiatric traits

Martin Broberg  1 , Viola Helaakoski  1 , Tuomo Kiiskinen  1 , Tiina Paunio  2   3 , Samuel E Jones  1 , Nina Mars  1 , Jacqueline M Lane  4 ; FinnGen; Richa Saxena  4   5   6   7 , Hanna M Ollila  1   5   6   7
Affiliations

Genetics of sleep medication purchases suggests causality from sleep problems to psychiatric traits

Martin Broberg et al. Sleep. .

Abstract

Study objectives: Over 10% of the population in Europe and in the United States use sleep medication to manage sleep problems. Our objective was to elucidate genetic risk factors and clinical correlates that contribute to sleep medication purchase and estimate the comorbid impact of sleep problems.

Methods: We performed epidemiological analysis for psychiatric diagnoses, and genetic association studies of sleep medication purchase in 797 714 individuals from FinnGen Release 7 (N = 311 892) and from the UK Biobank (N = 485 822). Post-association analyses included genetic correlation, co-localization, Mendelian randomization (MR), and polygenic risk estimation.

Results: In a GWAS we identified 27 genetic loci significantly associated with sleep medication, located in genes associated with sleep; AUTS2, CACNA1C, MEIS1, KIRREL3, PAX8, GABRA2, psychiatric traits; CACNA1C, HIST1H2BD, NUDT12. TOPAZ1 and TSNARE1. Co-localization and expression analysis emphasized effects on the KPNA2, GABRA2, and CACNA1C expression in the brain. Sleep medications use was epidemiologically related to psychiatric traits in FinnGen (OR [95% (CI)] = 3.86 [3.78 to 3.94], p < 2 × 10-16), and the association was accentuated by genetic correlation and MR; depression (rg = 0.55 (0.027), p = 2.86 × 10-89, p MR = 4.5 × 10-5), schizophrenia (rg = 0.25 (0.026), p = 2.52 × 10-21, p MR = 2 × 10-4), and anxiety (rg = 0.44 (0.047), p = 2.88 × 10-27, p MR = 8.6 × 10-12).

Conclusions: These results demonstrate the genetics behind sleep problems and the association between sleep problems and psychiatric traits. Our results highlight the scientific basis for sleep management in treating the impact of psychiatric diseases.

Keywords: genetics; insomnia; sleep hygiene.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
GWAS highlights distinct genetic patterns between males and females associating with sleep medication purchases. (A) Manhattan plot of the FinnGen study used in this investigation. (B) Miami plot of female and male-only subgroups of the total FinnGen R7 study. (C) LocusZoom plots of the lead SNPs rs2370413, rs279829, rs13262595, and rs1190734.
Figure 2.
Figure 2.
Mendelian randomization reveals causative links between sleep medication purchases and psychiatric traits. Scatter plots of MR results with sleep medication purchases as outcome against exposures/risk-factors anxiety, chronotype, depression, insomnia, multisite chronic pain (MCP), and schizophrenia. For the MCP analysis, only the weighted median and inverse-variance weighted were significant, while the negative trending MR Egger result was not significant.
See this image and copyright information in PMC

Comment in

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