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Education, intelligence and Alzheimer's disease: Evidence from a multivariable two-sample Mendelian randomization study

By Emma L Anderson, Laura D Howe, Kaitlin H Wade, Yoav Ben-Shlomo, W. David Hill, Ian J Deary, Eleanor C Sanderson, Jie Zheng, Roxanna Korologou-Linden, Evie Stergiakouli, George Davey Smith, Neil M Davies, Gibran Hemani

Posted 27 Aug 2018
bioRxiv DOI: 10.1101/401042

Background: Higher levels of educational attainment are associated with lower risk of dementia. However, the mechanisms underlying the association (for example, the role of education-related traits such as intelligence) are unknown. Identifying these mechanisms using observational methods is difficult due to bias from measurement error, confounding and reverse causation. Aims: To estimate the bidirectional causal effects of education on intelligence, and the total and independent effects of both education and intelligence on risk of Alzheimer's disease (AD). Methods: Using univariable and multivariable two-sample Mendelian randomization (MR) we estimated (i) the overall effect of educational attainment on intelligence and vice versa (ii) the overall effects of both educational attainment and intelligence on AD risk and (iii) the effects of educational attainment and intelligence on AD risk that are independent of the other trait. Results: There was strong evidence of a causal, bidirectional relationship between intelligence and educational attainment, with the magnitude of effect being similar in both directions after filtering SNPs to check they are instrumenting the correct exposure. 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, the odds of AD were, on average, 37% (95% CI: 23% to 49%) and 35% (95% CI: 25% to 43%) lower, respectively . There was little evidence from the multivariable MR analysis that educational attainment affected AD risk once intelligence was taken into account, but intelligence affected AD risk independently of educational attainment to a similar magnitude observed in the univariate analysis. Conclusions: There is robust evidence for an independent, causal effect of intelligence in lowering AD risk, potentially supporting a role for cognitive training interventions to improve aspects of intelligence. However, given the causal effect of educational attainment on intelligence observed in this analysis, there may also be support for policies aimed at increasing length of schooling to lower incidence of AD.

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