Abstract：
BACKGROUND: Major depression is a public health problem facing the world. This study aimed to identify the risk factors for major depression and clarify their causal effects.
METHODS: Data from the National Health and Nutrition Examination Survey (NHANES). Multifactorial logistic regression analysis was used to calculate the effect of each variable on major depression. Subgroup analyses and interaction tests were conducted to observe the stability of the association between them. Nonlinear correlations were explored using restricted cubic spline plots. The causal effects of serum Klotho on major depression were assessed using Mendelian randomization (MR) analysis.
RESULTS: A total of 8359 participated in the study. After adjusting for all covariates, the risk of having major depression was 1.47 times higher for each unit rise in serum Klotho (OR = 1.47, 95 % CI = 1.07-2.02; P = 0.0183). MR analysis showed no causal relationship between serum Klotho levels and risk of major depression (OR = 1.09, 95 % CI = 0.91-1.30; P = 0.4120). Sensitivity analysis verified the reliability of the results.
CONCLUSIONS: Serum Klotho is positively associated with an increased risk of major depression in the U.S. population, but MR analyses did not show genetic causality between Klotho and major depression in individuals of European ancestry. Based on the results of the current study, no indication maintaining high levels of Klotho may increase the risk of major depression.
CONCLUSIONS: The main limitation of this study is the inconsistency of the cross-sectional study and the MR population.
METHODS: Data from the National Health and Nutrition Examination Survey (NHANES). Multifactorial logistic regression analysis was used to calculate the effect of each variable on major depression. Subgroup analyses and interaction tests were conducted to observe the stability of the association between them. Nonlinear correlations were explored using restricted cubic spline plots. The causal effects of serum Klotho on major depression were assessed using Mendelian randomization (MR) analysis.
RESULTS: A total of 8359 participated in the study. After adjusting for all covariates, the risk of having major depression was 1.47 times higher for each unit rise in serum Klotho (OR = 1.47, 95 % CI = 1.07-2.02; P = 0.0183). MR analysis showed no causal relationship between serum Klotho levels and risk of major depression (OR = 1.09, 95 % CI = 0.91-1.30; P = 0.4120). Sensitivity analysis verified the reliability of the results.
CONCLUSIONS: Serum Klotho is positively associated with an increased risk of major depression in the U.S. population, but MR analyses did not show genetic causality between Klotho and major depression in individuals of European ancestry. Based on the results of the current study, no indication maintaining high levels of Klotho may increase the risk of major depression.
CONCLUSIONS: The main limitation of this study is the inconsistency of the cross-sectional study and the MR population.
摘要：
背景：重度抑郁症是全球面临的公共卫生问题。本研究旨在确定重度抑郁症的危险因素并阐明其因果关系。
方法：数据来自国家健康和营养调查（NHANES）。采用多因素logistic回归分析计算各变量对重度抑郁的影响。进行亚组分析和相互作用测试以观察它们之间关联的稳定性。使用有限的三次样条图探索了非线性相关性。使用孟德尔随机化（MR）分析评估血清Klotho对重度抑郁症的因果影响。
结果：共有8359人参与了这项研究。在调整所有协变量后，血清Klotho每升高一个单位,患重度抑郁症的风险就高1.47倍(OR=1.47,95%CI=1.07-2.02;P=0.0183).MR分析显示，血清Klotho水平与重度抑郁症的风险之间没有因果关系（OR=1.09，95％CI=0.91-1.30；P=0.4120）。灵敏度分析验证了结果的可靠性。
结论：血清Klotho与美国人群患重度抑郁症的风险增加呈正相关，但MR分析未显示Klotho与欧洲血统个体重度抑郁症之间的遗传因果关系.根据目前的研究结果，没有迹象表明维持高水平的Klotho可能会增加重度抑郁症的风险.
结论：本研究的主要局限性是横断面研究与MR人群的不一致。
方法：数据来自国家健康和营养调查（NHANES）。采用多因素logistic回归分析计算各变量对重度抑郁的影响。进行亚组分析和相互作用测试以观察它们之间关联的稳定性。使用有限的三次样条图探索了非线性相关性。使用孟德尔随机化（MR）分析评估血清Klotho对重度抑郁症的因果影响。
结果：共有8359人参与了这项研究。在调整所有协变量后，血清Klotho每升高一个单位,患重度抑郁症的风险就高1.47倍(OR=1.47,95%CI=1.07-2.02;P=0.0183).MR分析显示，血清Klotho水平与重度抑郁症的风险之间没有因果关系（OR=1.09，95％CI=0.91-1.30；P=0.4120）。灵敏度分析验证了结果的可靠性。
结论：血清Klotho与美国人群患重度抑郁症的风险增加呈正相关，但MR分析未显示Klotho与欧洲血统个体重度抑郁症之间的遗传因果关系.根据目前的研究结果，没有迹象表明维持高水平的Klotho可能会增加重度抑郁症的风险.
结论：本研究的主要局限性是横断面研究与MR人群的不一致。
