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Abstract：
BACKGROUND: Depression and chronic pain are significant contributors to the global burden of disease. Previous research has revealed complex relationships between these two conditions, which may be influenced by sleep quality. However, observational studies have limitations, including confounding factors and reverse causation. This study aims to explore the mediating effects of sleep on the relationship between depression and chronic pain using Mendelian randomization (MR).
METHODS: We conducted a two-step, two-sample MR study using mediation analysis. We obtained major depressive disorder (MDD) Genome-Wide Association Studdies (GWAS) data from Wray et al.\'s GWAS meta-analysis. Phenotypic data related to sleep were collected from the UK Biobank. Chronic pain data were obtained from the Finnish database.
RESULTS: MR analysis revealed significant genetic associations between MDD and chronic localized pain [IVW: odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.16-1.38, p = 2.52 × 10-7] as well as fibromyalgia (IVW: OR = 2.17, 95% CI = 1.34-3.52, p = .002). Genetic susceptibility for MDD was also associated with insomnia (IVW: OR = 1.10, 95% CI = 1.06-1.13, p = 3.57 × 10-8) and self-reported short sleep duration (IVW: OR = 1.03, 95% CI = 1.00-1.06, p = .047). The mediating effects of insomnia and fibromyalgia on the pathway from depression to chronic regional pain were 1.04 and 1.03, respectively, with mediation proportions of 12.8% and 15.2%. Insomnia mediated the pathway between depression and fibromyalgia with an effect of 1.12, accounting for 15.2% of the total effect.
CONCLUSIONS: This two-step MR analysis strengthens the evidence of genetic predictive associations between depression and chronic pain, highlighting the mediating roles of insomnia and short sleep duration. It further elucidates the specific roles of distinct sleep disorders, differentiating insomnia and short sleep duration from other sleep-related phenotypes.
METHODS: We conducted a two-step, two-sample MR study using mediation analysis. We obtained major depressive disorder (MDD) Genome-Wide Association Studdies (GWAS) data from Wray et al.\'s GWAS meta-analysis. Phenotypic data related to sleep were collected from the UK Biobank. Chronic pain data were obtained from the Finnish database.
RESULTS: MR analysis revealed significant genetic associations between MDD and chronic localized pain [IVW: odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.16-1.38, p = 2.52 × 10-7] as well as fibromyalgia (IVW: OR = 2.17, 95% CI = 1.34-3.52, p = .002). Genetic susceptibility for MDD was also associated with insomnia (IVW: OR = 1.10, 95% CI = 1.06-1.13, p = 3.57 × 10-8) and self-reported short sleep duration (IVW: OR = 1.03, 95% CI = 1.00-1.06, p = .047). The mediating effects of insomnia and fibromyalgia on the pathway from depression to chronic regional pain were 1.04 and 1.03, respectively, with mediation proportions of 12.8% and 15.2%. Insomnia mediated the pathway between depression and fibromyalgia with an effect of 1.12, accounting for 15.2% of the total effect.
CONCLUSIONS: This two-step MR analysis strengthens the evidence of genetic predictive associations between depression and chronic pain, highlighting the mediating roles of insomnia and short sleep duration. It further elucidates the specific roles of distinct sleep disorders, differentiating insomnia and short sleep duration from other sleep-related phenotypes.
摘要：
背景：抑郁症和慢性疼痛是全球疾病负担的重要因素。先前的研究揭示了这两个条件之间的复杂关系，这可能会受到睡眠质量的影响。然而,观察性研究有局限性，包括混杂因素和反向因果关系。本研究旨在通过孟德尔随机化(MR)探讨睡眠在抑郁与慢性疼痛关系中的中介作用。
方法：我们进行了两步，使用中介分析的双样本MR研究。我们从Wray等人获得了重度抑郁症（MDD）全基因组关联研究（GWAS）数据。GWAS荟萃分析。从英国生物库收集与睡眠相关的表型数据。慢性疼痛数据来自芬兰数据库。
结果：MR分析显示，MDD与慢性局部疼痛[IVW：比值比（OR）=1.26，95％置信区间（CI）=1.16-1.38，p=2.52×10-7]以及纤维肌痛（IVW：OR=2.17，95％CI=1.34-3.52，p=0.002）之间存在显着的遗传关联。MDD的遗传易感性还与失眠（IVW：OR=1.10，95％CI=1.06-1.13，p=3.57×10-8）和自我报告的短睡眠时间（IVW：OR=1.03，95％CI=1.00-1.06，p=0.047）有关。失眠和纤维肌痛在抑郁到慢性局部疼痛通路中的中介作用分别为1.04和1.03,调解比例分别为12.8%和15.2%。失眠介导抑郁与纤维肌痛之间的通路效应为1.12，占总效应的15.2%。
结论：这种两步MR分析加强了抑郁症和慢性疼痛之间遗传预测关联的证据，强调失眠和睡眠时间短的中介作用。它进一步阐明了不同睡眠障碍的具体作用，将失眠和睡眠持续时间短与其他睡眠相关表型区分开来。
方法：我们进行了两步，使用中介分析的双样本MR研究。我们从Wray等人获得了重度抑郁症（MDD）全基因组关联研究（GWAS）数据。GWAS荟萃分析。从英国生物库收集与睡眠相关的表型数据。慢性疼痛数据来自芬兰数据库。
结果：MR分析显示，MDD与慢性局部疼痛[IVW：比值比（OR）=1.26，95％置信区间（CI）=1.16-1.38，p=2.52×10-7]以及纤维肌痛（IVW：OR=2.17，95％CI=1.34-3.52，p=0.002）之间存在显着的遗传关联。MDD的遗传易感性还与失眠（IVW：OR=1.10，95％CI=1.06-1.13，p=3.57×10-8）和自我报告的短睡眠时间（IVW：OR=1.03，95％CI=1.00-1.06，p=0.047）有关。失眠和纤维肌痛在抑郁到慢性局部疼痛通路中的中介作用分别为1.04和1.03,调解比例分别为12.8%和15.2%。失眠介导抑郁与纤维肌痛之间的通路效应为1.12，占总效应的15.2%。
结论：这种两步MR分析加强了抑郁症和慢性疼痛之间遗传预测关联的证据，强调失眠和睡眠时间短的中介作用。它进一步阐明了不同睡眠障碍的具体作用，将失眠和睡眠持续时间短与其他睡眠相关表型区分开来。
