Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Olle Melander

Principal investigator

Default user image.

Metabolic Mediators of the Effects of Family History and Genetic Risk Score on Coronary Heart Disease-Findings from the Malmö Diet and Cancer Study

Author

  • Josef Fritz
  • Dov Shiffman
  • Olle Melander
  • Hayato Tada
  • Hanno Ulmer

Summary, in English

Background--Family history of coronary heart disease (CHD) as well as genetic predisposition to CHD assessed by a genetic risk score (GRS) are predictors of CHD risk. It is, however, uncertain to what extent these risk predictors are mediated by major metabolic pathways. Methods and Results--Total effects of self-reported family history and a 50-variant GRS (GRS50), as well as effects mediated by apolipoprotein B and A-I (apoB, apoA-I), blood pressure, and diabetes mellitus, on incidence of CHD were estimated in 23 595 participants of the Malmö Diet and Cancer study (a prospective, population-based study). During a median follow-up of 14.4 years, 2213 participants experienced a first CHD event. Family history of CHD and GRS50 (highest versus other quintiles) were associated with incident CHD, with hazard ratios of 1.52 (95% CI: 1.39-1.65) and 1.53 (95% CI: 1.39-1.68), respectively, after adjusting for age, sex, and smoking status. Small proportions of the family history effect were mediated by metabolic risk factors: 8.3% (95% CI: 5.8-11.7%) by the apoB pathway, 1.7% (95% CI: 0.2-3.4%) by apoA-I, 8.5% (95% CI: 5.9-12.0%) by blood pressure, and 1.5% (95% CI: 0.8% to 3.8%) by diabetes mellitus. Similarly, small proportions of GRS50 were mediated: 8.1% (95% CI: 5.5-11.8%) by apoB, 1.2% (95% CI: 0.5-3.0%) by apoA-I, 4.2% (95% CI: 1.3-7.5%) by blood pressure, and 0.9% (95% CI: 3.7% to 1.6%) by diabetes mellitus. Conclusions--A fraction of the CHD risk associated with family history or with GRS50 is mediated through elevated blood lipids and hypertension, but not through diabetes mellitus. However, a major part (≥80%) of the genetic effect operates independently of established metabolic risk factor pathways.

Department/s

  • Cardiovascular Research - Hypertension
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2017

Language

English

Publication/Series

Journal of the American Heart Association

Volume

6

Issue

3

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Cardiac and Cardiovascular Systems

Keywords

  • Coronary heart disease
  • Epidemiology
  • Family history
  • Genetic association
  • Risk factor

Status

Published

Research group

  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 2047-9980