Educational attainment as a modifier for the effect of polygenic scores for cardiovascular risk factors: cross-sectional and prospective analysis of UK Biobank

Author:

Carter Alice R12ORCID,Harrison Sean12ORCID,Gill Dipender3456ORCID,Davey Smith George127ORCID,Taylor Amy E127,Howe Laura D12,Davies Neil M128ORCID

Affiliation:

1. MRC Integrative Epidemiology Unit, University of Bristol Bristol, UK

2. Population Health Sciences, Bristol Medical School, University of Bristol , Bristol, UK

3. Clinical Pharmacology and Therapeutics Section, Institute of Medical and Biomedical Education and Institute for Infection and Immunity, St George’s, University of London , London, UK

4. Clinical Pharmacology Group, Pharmacy and Medicines Directorate, St George’s University Hospitals NHS Foundation Trust , London, UK

5. Novo Nordisk Research Centre Oxford, Old Road Campus , Oxford, UK

6. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London , London, UK

7. NIHR Bristol Biomedical Research Centre, University of Bristol , Bristol, UK

8. K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology , Trondheim, Norway

Abstract

Abstract Background Understanding the interplay between educational attainment and genetic predictors of cardiovascular risk may improve our understanding of the aetiology of educational inequalities in cardiovascular disease. Methods In up to 320 120 UK Biobank participants of White British ancestry (mean age = 57 years, female 54%), we created polygenic scores for nine cardiovascular risk factors or diseases: alcohol consumption, body mass index, low-density lipoprotein cholesterol, lifetime smoking behaviour, systolic blood pressure, atrial fibrillation, coronary heart disease, type 2 diabetes and stroke. We estimated whether educational attainment modified genetic susceptibility to these risk factors and diseases. Results On the additive scale, higher educational attainment reduced genetic susceptibility to higher body mass index, smoking, atrial fibrillation and type 2 diabetes, but increased genetic susceptibility to higher LDL-C and higher systolic blood pressure. On the multiplicative scale, there was evidence that higher educational attainment increased genetic susceptibility to atrial fibrillation and coronary heart disease, but little evidence of effect modification was found for all other traits considered. Conclusions Educational attainment modifies the genetic susceptibility to some cardiovascular risk factors and diseases. The direction of this effect was mixed across traits considered and differences in associations between the effect of the polygenic score across strata of educational attainment was uniformly small. Therefore, any effect modification by education of genetic susceptibility to cardiovascular risk factors or diseases is unlikely to substantially explain the development of inequalities in cardiovascular risk.

Funder

UK Medical Research Council Integrative Epidemiology Unit

University of Bristol

British Heart Foundation University of Bristol Accelerator Award

UK Medical Research Council and University of Bristol

British Heart Foundation Centre of Research Excellence

Imperial College London and a National Institute for Health Research Clinical Lectureship

Publisher

Oxford University Press (OUP)

Subject

General Medicine,Epidemiology

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