Evidence for causal effects of sleep disturbances on risk for osteoarthritis: a univariable and multivariable Mendelian randomization study

Dec 10, 2021Osteoarthritis and cartilage

Sleep problems may increase the risk of osteoarthritis: genetic analysis using single and multiple factors

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Abstract

Genetically determined insomnia is associated with a 22% increased risk of osteoarthritis.

Genetic factors linked to insomnia and short sleep duration may have a causal effect on the risk of osteoarthritis.
The odds ratio for insomnia was 1.22, indicating a significant association with osteoarthritis risk.
Short sleep duration was associated with an odds ratio of 1.04 for osteoarthritis, suggesting a potential adverse effect.
Increasing genetic liability to insomnia or short sleep duration remained linked to osteoarthritis risk even when considering body mass index, type 2 diabetes, and depression.
Findings indicate that addressing sleep disturbances could be important for reducing the risk of osteoarthritis.

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OBJECTIVE: To disentangle whether sleep disturbances have a causal effect on the risk of osteoarthritis (OA) using genetically based approaches.

METHOD: We performed univariable and multivariable Mendelian randomization (MR) analyses using publicly released genome-wide association studies summary statistics to estimate the causal associations of sleep disturbances with OA risk. The inverse-variance weighted (IVW) method was utilized as primary MR analysis, whereas complementary methods including weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO) were applied to detect and correct for the presence of pleiotropy.

RESULTS: There were 228 independent instrumental variables (IVs) for insomnia and 78, 27 and 8 IVs for sleep duration, short sleep duration and long sleep duration, respectively. Univariable MR analysis suggested that genetically determined insomnia or short sleep duration exerted a causal effect on overall OA in an unfavorable manner (Insomnia: OR = 1.22, 95%CI = 1.15-1.30, P = 8.05 × 10; Short sleep duration: OR = 1.04, 95%CI = 1.02-1.07, P = 2.20 × 10). More compelling, increasing genetic liability to insomnia or short sleep duration was also associated with OA risk, after accounting for effects of insomnia or short sleep duration on body mass index, type 2 diabetes and depression individually, and in a combined model considering all three confounders. -10 -3

CONCLUSIONS: Findings suggested consisted evidence for an adverse effect of increased insomnia or short sleep duration on OA risk. Strategies to mitigate sleep disturbances may be one of the cornerstones protects against OA.

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Evidence for causal effects of sleep disturbances on risk for osteoarthritis: a univariable and multivariable Mendelian randomization study

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