Objective To determine whether educational attainment is a causal risk factor in the development of coronary heart disease.Design Mendelian randomisation study, using genetic data as proxies for education to minimise confounding.Setting The main analysis used genetic data from two large consortia (CARDIoGRAMplusC4D and SSGAC), comprising 112 studies from predominantly high income countries. Findings from mendelian randomisation analyses were then compared against results from traditional observational studies (164 170 participants). Finally, genetic data from six additional consortia were analysed to investigate whether longer education can causally alter the common cardiovascular risk factors.Participants The main analysis was of 543 733 men and women (from CARDIoGRAMplusC4D and SSGAC), predominantly of European origin.Exposure A one standard deviation increase in the genetic predisposition towards higher education (3.6 years of additional schooling), measured by 162 genetic variants that have been previously associated with education.Main outcome measure Combined fatal and non-fatal coronary heart disease (63 746 events in CARDIoGRAMplusC4D).Results Genetic predisposition towards 3.6 years of additional education was associated with a one third lower risk of coronary heart disease (odds ratio 0.67, 95% confidence interval 0.59 to 0.77; P=3×10-8). This was comparable to findings from traditional observational studies (prevalence odds ratio 0.73, 0.68 to 0.78; incidence odds ratio 0.80, 0.76 to 0.83). Sensitivity analyses were consistent with a causal interpretation in which major bias from genetic pleiotropy was unlikely, although this remains an untestable possibility. Genetic predisposition towards longer education was additionally associated with less smoking, lower body mass index, and a favourable blood lipid profile.Conclusions This mendelian randomisation study found support for the hypothesis that low education is a causal risk factor in the development of coronary heart disease. Potential mechanisms could include smoking, body mass index, and blood lipids. In conjunction with the results from studies with other designs, these findings suggest that increasing education may result in substantial health benefits.

Centre for Environmental Health Monitoring National Institute of Public Health Prague Czech Republic

Chair of Epidemiology and Population Studies Institute of Public Health Faculrty of Health Sciences Jagiellonian University Medical College Krakow Poland

Clinical Trial Service Unit and Epidemiological Studies Unit Nuffield Department of Population Health Big Data Institute University of Oxford Oxford UK

Department of Complex Trait Genetics Vrije Universiteit Amsterdam Amsterdam Netherlands

Department of Epidemiology and Public Health University College London London UK

Department of Internal Medicine Lausanne University Hospital Lausanne Switzerland

Department of Mathematics and Statistics Lancaster University Lancaster UK

Estonian Genome Center University of Tartu Tartu Estonia

Institute of Cardiology Lithuanian University of Health Sciences Kaunas Lithuania

Medical Research Council Integrative Epidemiology Unit at the University of Bristol Bristol UK

Medical Research Council Population Health Research Unit at the University of Oxford Oxford UK

National Institute for Health Research Oxford Biomedical Research Centre Oxford University Hospital Oxford UK

Novosibirsk State Medical University Novosibirsk Russia

Postgraduate Programme in Epidemiology Federal University of Pelotas Pelotas Brazil

Research Center in Epidemiology and Preventive Medicine University of Insubria Varese Italy

Research Institute of Internal and Preventive Medicine Branch of the Institute of Cytology and Genetics SB RAS Novosibirsk Russia

School of Social and Community Medicine University of Bristol Bristol UK

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BMJ. 2017 Aug 30;358:j3849. doi: 10.1136/bmj.j3849. PubMed

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