使用两样本孟德尔随机化研究收入对健康的因果效应。
Investigating causal effects of income on health using two-sample Mendelian randomisation.
作者信息
Igelström Erik, Munafò Marcus R, Brumpton Ben M, Davies Neil M, Davey Smith George, Martikainen Pekka, Campbell Desmond, Craig Peter, Lewsey Jim, Katikireddi S Vittal
机构信息
MRC/CSO Social and Public Health Sciences Unit, School of Health and Wellbeing, University of Glasgow, Glasgow, UK.
MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Bristol, UK.
出版信息
BMC Glob Public Health. 2025 Feb 10;3(1):12. doi: 10.1186/s44263-025-00130-4.
BACKGROUND
Income is associated with many health outcomes, but it is unclear how far this reflects a causal relationship. Mendelian randomisation (MR) uses genetic variation between individuals to investigate causal effects and may overcome some of the confounding issues inherent in many observational study designs.
METHODS
We used two-sample MR using data from unrelated individuals to estimate the effect of log occupational income on indicators of mental health, physical health, and health-related behaviours. We investigated pleiotropy (direct effects of genotype on the outcome) using robust MR estimators, CAUSE, and multivariable MR including education as a co-exposure. We also investigated demographic factors and dynastic effects using within-family analyses, and misspecification of the primary phenotype using bidirectional MR and Steiger filtering.
RESULTS
We found that a 10% increase in income lowered the odds of depression (OR 0.92 [95% CI 0.86-0.98]), death (0.91 [0.86-0.96]), and ever-smoking (OR 0.91 [0.86-0.96]), and reduced BMI (- 0.06 SD [- 0.11, - 0.003]). We found little evidence of an effect on alcohol consumption (- 0.02 SD [- 0.01, 0.05]) or subjective wellbeing (0.02 SD [- 0.003, 0.04]), or on two negative control outcomes, childhood asthma (OR 0.99 [0.87, 1.13]) and birth weight (- 0.02 SD, [- 0.01, 0.05]). Within-family analysis and multivariable MR including education and income were imprecise, and there was substantial overlap between the genotypes associated with income and education: out of 36 genetic variants significantly associated with income, 29 were also significantly associated with education.
CONCLUSIONS
MR evidence provides some limited support for causal effects of income on some mental health outcomes and health behaviours, but the lack of reliable evidence from approaches accounting for family-level confounding and potential pleiotropic effects of education places considerable caveats on this conclusion. MR may nevertheless be a useful complement to other observational study designs since its assumptions and limitations are radically different. Further research is needed using larger family-based genetic cohorts, and investigating the overlap between income and other socioeconomic measures.
背景
收入与多种健康结果相关，但尚不清楚这在多大程度上反映了因果关系。孟德尔随机化（MR）利用个体间的基因变异来研究因果效应，可能克服许多观察性研究设计中固有的一些混杂问题。
方法
我们使用两样本孟德尔随机化方法，利用无关个体的数据来估计对数职业收入对心理健康、身体健康和健康相关行为指标的影响。我们使用稳健的孟德尔随机化估计器、CAUSE以及包括教育作为共同暴露因素的多变量孟德尔随机化来研究基因多效性（基因型对结果的直接影响）。我们还使用家庭内部分析研究人口统计学因素和家族效应，并使用双向孟德尔随机化和施泰格过滤来研究主要表型的错误设定。
结果
我们发现收入增加10%会降低患抑郁症的几率（比值比0.92 [95%置信区间0.86 - 0.98]）、死亡几率（0.91 [0.86 - 0.96]）和曾经吸烟的几率（比值比0.91 [0.86 - 0.96]），并降低体重指数（-0.06标准差[-0.11, -0.003]）。我们几乎没有发现对饮酒量（-0.02标准差[-0.01, 0.05]）或主观幸福感（0.02标准差[-0.003, 0.04]）有影响的证据，也没有发现对两个阴性对照结果，即儿童哮喘（比值比0.99 [0.87, 1.13]）和出生体重（-0.02标准差，[-0.01, 0.05]）有影响的证据。家庭内部分析以及包括教育和收入的多变量孟德尔随机化并不精确，并且与收入和教育相关的基因型之间存在大量重叠：在36个与收入显著相关的基因变异中，有29个也与教育显著相关。
结论
孟德尔随机化证据为收入对某些心理健康结果和健康行为的因果效应提供了一些有限的支持，但考虑家庭层面混杂因素和教育潜在基因多效性效应的方法缺乏可靠证据，这给该结论带来了相当大的限制。然而，孟德尔随机化可能是其他观察性研究设计的有用补充，因为其假设和局限性截然不同。需要使用更大的基于家庭的基因队列进行进一步研究，并调查收入与其他社会经济指标之间的重叠情况。
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