Education, intelligence and Alzheimer's disease: Evidence from a multivariable two-sample Mendelian randomization study
Education, intelligence and Alzheimer's disease: Evidence from a multivariable two-sample Mendelian randomization study
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教育、智力和阿尔茨海默病：来自多变量两样本孟德尔随机化研究的证据
DOI：
10.1101/401042
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Anderson E
中科院分区：
文献类型：
--
作者：
Anderson E
目的检验教育程度和智力对阿尔茨海默病(AD)发病风险的因果效应是否相互独立。设计两个样本单变量和多变量孟德尔随机化(MR)来估计教育对智力的因果效应，反之亦然。以及教育和智力对AD风险的总体和独立的因果关系。来自国际阿尔茨海默氏症计划(IGAP)财团的17,008例AD病例和37,154名对照。主要结果测量AD在受教育年限(SD = 3.6年 年)和智力(SD=15分智力测试)的标准偏差增加的奇比(OR)。结果有强有力的证据表明，智力和教育程度之间存在因果的双向关系，两个方向的影响程度相似[教育智力OR=0.51SD单位，95%可信区间(CI)：0.49，0.54；或智力教育=0.57 SD单位，95%CI：0.48，0.66]。在单变量MR分析中，教育程度和智力对AD风险的总体影响相似；受教育年限和智力每增加一次SD，AD的患病几率平均降低37%(95%可信区间：23-49%)和35%(95%可信区间：25-43%)。在多变量MR分析中，几乎没有证据表明教育程度对AD风险有影响(OR = 1.15，95%CI：0.68-1.93)，但在单变量分析中，智力对AD风险的影响独立于教育程度(OR = 0.69，95%CI：0.44-0.88)。结论有强有力的证据表明智力在降低AD风险方面具有独立的因果效应。受教育程度对阿尔茨海默病风险的因果影响很可能是通过智力来调节的。
ObjectivesTo examine whether educational attainment and intelligence have causal effects on risk of Alzheimer’s disease (AD), independently of each other.DesignTwo-sample univariable and multivariable Mendelian randomization (MR) to estimate the causal effects of education on intelligence and vice versa, and the total and independent causal effects of both education and intelligence on AD risk.Participants17 008 AD cases and 37 154 controls from the International Genomics of Alzheimer’s Project (IGAP) consortium.Main outcome measureOdds ratio (OR) of AD per standardized deviation increase in years of schooling (SD = 3.6 years) and intelligence (SD = 15 points on intelligence test).ResultsThere was strong evidence of a causal, bidirectional relationship between intelligence and educational attainment, with the magnitude of effect being similar in both directions [OR for intelligence on education = 0.51 SD units, 95% confidence interval (CI): 0.49, 0.54; OR for education on intelligence = 0.57 SD units, 95% CI: 0.48, 0.66]. Similar overall effects were observed for both educational attainment and intelligence on AD risk in the univariable MR analysis; with each SD increase in years of schooling and intelligence, odds of AD were, on average, 37% (95% CI: 23–49%) and 35% (95% CI: 25–43%) lower, respectively. There was little evidence from the multivariable MR analysis that educational attainment affected AD risk once intelligence was taken into account (OR = 1.15, 95% CI: 0.68–1.93), but intelligence affected AD risk independently of educational attainment to a similar magnitude observed in the univariate analysis (OR = 0.69, 95% CI: 0.44–0.88).ConclusionsThere is robust evidence for an independent, causal effect of intelligence in lowering AD risk. The causal effect of educational attainment on AD risk is likely to be mediated by intelligence.