Bidirectional Mendelian randomization of childhood maltreatment and sleep-related phenotypes.

چکیده اصلی

Background: Childhood maltreatment (CM) is associated with sleep disturbance, but observational findings may be affected by confounding, shared familial liability, and reverse-direction explanations. We conducted bidirectional two-sample Mendelian randomization (MR) to examine genetic evidence linking composite CM liability with six sleep-related phenotypes.Methods: Genetic instruments for CM were obtained from a large European-ancestry multi-cohort GWAS meta-analysis. CM was defined as a composite phenotype encompassing multiple abuse and neglect subtypes and ascertainment modes. Summary statistics for chronotype, daytime sleepiness (DS), insomnia symptoms, sleep apnea (SA), daytime napping (DN), and sleep duration (SD) were derived from large European-ancestry GWASs. Inverse-variance weighted MR was the primary method, with weighted median and MR-Egger sensitivity analyses. Benjamini-Hochberg correction was applied and reported as P(BH).Results: In forward MR, genetically proxied CM was associated with higher DS (OR = 1.04, 95% CI 1.01-1.07; P(BH) = 0.030), insomnia symptoms (OR = 1.08, 95% CI 1.01-1.15; P(BH) = 0.030), and DN (β = 0.07, 95% CI 0.03-0.09; P(BH) = 0.002). Little evidence was observed for chronotype, SA, or SD. In exploratory reverse-direction MR, genetic liability to DN (β = 0.16, 95% CI 0.05-0.27; P(BH) = 0.012) and insomnia symptoms (β = 0.21, 95% CI 0.07-0.35; P(BH) = 0.012) was associated with CM liability.Conclusions: This study provides suggestive genetic evidence linking composite CM liability with selected sleep-related phenotypes, particularly self-reported DS, insomnia symptoms, and DN. Reverse-direction findings may reflect shared genetic liability, gene-environment correlation, reporting-related mechanisms, or broader familial pathways rather than temporal effects of adult sleep traits on CM. Given modest effects and uneven sensitivity support, findings should be interpreted cautiously.

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