Education, intelligence and Alzheimer’s disease: evidence from a multivariable two-sample Mendelian randomization study
Year: 2020
Type: article
Study design: Observational Study
Abstract: OBJECTIVES: To examine whether educational attainment and intelligence have causal effects on risk of Alzheimer's disease (AD), independently of each other. DESIGN: Two-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. PARTICIPANTS: 17 008 AD cases and 37 154 controls from the International Genomics of Alzheimer's Project (IGAP) consortium. MAIN OUTCOME MEASURE: Odds ratio (OR) of AD per standardized deviation increase in years of schooling (SD = 3.6 years) and intelligence (SD = 15 points on intelligence test). 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 [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). CONCLUSIONS: There 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.
DOI: 10.1093/ije/dyz280
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,514
Awards: G1182606701, The causal map of the human phenome, G2451167502, G2452660645, G2538597952, Early life adversity and trajectories of cardiometabolic health, cognitive function and physical function: improving understanding of the mechanisms and potential reversibility, G2957837340, G3233549029, G3288322216, G339059223, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi- generation, longitudinal resource focusing on life course health and well- being., G3696935633, Informing educational interventions using genome-wide data: causal evidence from 573,586 participants of eight cohort studies, What lies behind the causal impact of body mass index (BMI) level and change on human health? Added value from complementary study design and deep metabolomic phenotyping., G5067462658, The causal map of the human phenome, G5470336846, Life course aetiology of dementia and cognitive decline: improving causal inference, G5728235598, G6285097384, Early life adversity and trajectories of cardiometabolic health, cognitive function and physical function: improving understanding of the mechanisms a, G6689231961, Mendelian randomization to hypothesis-free causal inference, G7448564355, Mediation analysis in life course epidemiology: methodological innovation and application to studies of obesity and cardiometabolic health, G7990456425, What lies behind the causal impact of body mass index (BMI) level and change on human health? Added value from complementary study design and deep metabolomic phenotyping., G8502142660, G8907334132
OpenAlex ID: W3003878943