Table_6_Causal effects of socioeconomic traits on frailty: a Mendelian randomization study.DOCX

BackgroundThe relationship between socioeconomic status and frailty has been extensively investigated in the literature, but it remains unclear whether a causal relationship exists. Our goal is to evaluate the causal relationship between six socioeconomic traits and the frailty index using summary-level data for single nucleotide polymorphisms from large genome-wide association studies with individuals of European ancestry.MethodsA two-sample MR was performed. We applied the inverse variance weighted (IVW) method for the primary estimate, with sensitivity analyses conducted using alternative MR methods to evaluate the robustness of the findings. A subsequent multivariable MR was undertaken to adjust for the effects of body mass index (BMI). Finally, the MR Steiger directionality test was performed to confirm the causal direction.ResultsThe IVW MR analysis revealed significant associations between various socioeconomic factors and the frailty index. Specifically, genetically predicated age completed full time education (β = −0.477, 95% confidence interval [CI]: −0.634 to −0.319) and average total household income before tax (β = −0.321, 95% CI: −0.410 to −0.232) were negatively associated with the frailty index. On the other hand, genetically predicted job involves heavy manual or physical work (β = 0.298, 95% CI: 0.113 to 0.484), job involves mainly walking or standing (β = 0.179, 95% CI: 0.013 to 0.345), Townsend deprivation index at recruitment (β = 0.535, 95% CI: 0.285 to 0.785), and social isolation/loneliness (β = 1.344, 95% CI: 0.834 to 1.853) were positively associated with the frailty index. Sensitivity analysis using other MR methods and multivariable MR analysis adjusting for BMI yielded stable results. The MR Steiger directionality test confirmed the causal direction.ConclusionOur findings highlight the importance of socioeconomic factors in affecting frailty risk. Future research should focus on unraveling the pathways through which these socioeconomic factors exert their effects on frailty, with the ultimate goal of developing targeted strategies to mitigate the risk of frailty.

背景社会经济地位与脆弱性之间的关系在文献中已得到广泛探讨，然而，是否存在因果关系仍不明确。本研究旨在评估六个社会经济特征与脆弱性指数之间的因果关系，通过使用来自大型全基因组关联研究（涉及欧洲血统个体）的单核苷酸多态性水平数据的汇总数据进行分析。方法我们进行了双样本孟德尔随机化分析。对主要估计值，我们采用了逆方差加权法（IVW），并使用其他孟德尔随机化方法进行敏感性分析，以评估结果的稳健性。随后，进行了多变量孟德尔随机化分析，以调整体重指数（BMI）的影响。最后，通过孟德尔随机化Steiger方向性检验，以确认因果方向。结果IVW孟德尔随机化分析揭示了各种社会经济因素与脆弱性指数之间的显著关联。具体而言，基于遗传的完成全职教育年龄（β = −0.477，95%置信区间[CI]：−0.634至−0.319）和税前平均总家庭收入（β = −0.321，95%置信区间[CI]：−0.410至−0.232）与脆弱性指数呈负相关。另一方面，基于遗传的涉及重体力劳动或物理劳动的工作（β = 0.298，95%置信区间[CI]：0.113至0.484）、主要涉及行走或站立的工作（β = 0.179，95%置信区间[CI]：0.013至0.345）、招募时的Townsend剥夺指数（β = 0.535，95%置信区间[CI]：0.285至0.785）以及社会隔离/孤独感（β = 1.344，95%置信区间[CI]：0.834至1.853）与脆弱性指数呈正相关。使用其他孟德尔随机化方法进行的敏感性分析和调整BMI的多变量孟德尔随机化分析产生了稳定的结果。孟德尔随机化Steiger方向性检验确认了因果方向。结论我们的研究结果突出了社会经济因素在影响脆弱性风险中的重要性。未来的研究应专注于揭示这些社会经济因素如何通过何种途径影响脆弱性，最终目标是开发针对性的策略以减轻脆弱性的风险。