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Joint association between education and polygenic risk score for incident coronary heart disease events: a longitudinal population-based study of 26 203 men and women
  1. Pekka Martikainen1,2,3,
  2. Kaarina Korhonen1,
  3. Aline Jelenkovic4,5,
  4. Hannu Lahtinen1,
  5. Aki Havulinna6,7,
  6. Samuli Ripatti5,6,8,
  7. Katja Borodulin7,9,
  8. Veikko Salomaa7,
  9. George Davey Smith10,
  10. Karri Silventoinen1
  1. 1Population Research Unit, University of Helsinki Faculty of Social Sciences, Helsinki, Finland
  2. 2Centre for Health Equity Studies, Stockholm University, Stockholm, Sweden
  3. 3Max Planck Institute for Demographic Research, Rostock, Germany
  4. 4Department of Physiology, University of the Basque Country, Bilbao, País Vasco, Spain
  5. 5Department of Public Health, Faculty of Medicine, University of Helsinki, Helsinki, Finland
  6. 6Institute for Molecular Medicine Finland, Helsinki, Finland
  7. 7Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Uusimaa, Finland
  8. 8Broad Institute of MIT and Harvard, Cambridge, MA, USA
  9. 9Age Institute, Helsinki, Finland
  10. 10Department of Social Medicine, University of Bristol, Bristol, Bristol, UK
  1. Correspondence to Professor Pekka Martikainen, Population Research Unit, University of Helsinki Faculty of Social Sciences, Helsinki, Finland; pekka.martikainen{at}helsinki.fi

Abstract

Background Genetic vulnerability to coronary heart disease (CHD) is well established, but little is known whether these effects are mediated or modified by equally well-established social determinants of CHD. We estimate the joint associations of the polygenetic risk score (PRS) for CHD and education on CHD events.

Methods The data are from the 1992, 1997, 2002, 2007 and 2012 surveys of the population-based FINRISK Study including measures of social, behavioural and metabolic factors and genome-wide genotypes (N=26 203). Follow-up of fatal and non-fatal incident CHD events (N=2063) was based on nationwide registers.

Results Allowing for age, sex, study year, region of residence, study batch and principal components, those in the highest quartile of PRS for CHD had strongly increased risk of CHD events compared with the lowest quartile (HR=2.26; 95% CI: 1.97 to 2.59); associations were also observed for low education (HR=1.58; 95% CI: 1.32 to 1.89). These effects were largely independent of each other. Adjustment for baseline smoking, alcohol use, body mass index, igh-density lipoprotein (HDL) and total cholesterol, blood pressure and diabetes attenuated the PRS associations by 10% and the education associations by 50%. We do not find strong evidence of interactions between PRS and education.

Conclusions PRS and education predict CHD events, and these associations are independent of each other. Both can improve CHD prediction beyond behavioural risks. The results imply that observational studies that do not have information on genetic risk factors for CHD do not provide confounded estimates for the association between education and CHD.

  • social epidemiology
  • gene environment interactions
  • education
  • coronary heart disease
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Footnotes

  • Contributors All authors contributed to the study design, interpretation and revising of the manuscript and approved the final version. PM drafted the first version of the manuscript. KK and AH carried out the analyses.

  • Funding This work was supported by grants 308247 and 294861 from the Academy of Finland, Horizon 2020 innovation action award number 667661 from the European Commission (project MINDMAP) and the Finnish Foundation for Cardiovascular Research.

  • Competing interests VS reports personal fees and non-financial support from Novo Nordisk, personal fees from Sanofi and grants from Bayer, outside the scope of the submitted work. All the other authors have nothing further to declare.

  • Patient consent for publication Not required.

  • Ethics approval Ethical approval has been obtained according to required procedures over the study years. The Coordinating Ethics Committee of the Helsinki and Uusimaa Hospital District approved the study, which followed the Declaration of Helsinki.

  • Data availability statement Data may be obtained from a third party and are not publicly available. FINRISK data are available from the THL Biobank based on written application and following the instructions given in the website of the Biobank (https://thl.fi/en/web/thl-biobank/for-researchers).

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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