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.

Chromosome 9p21 genetic variation explains 13% of cardiovascular disease incidence but does not improve risk prediction.

Author

  • Klas Gränsbo
  • Peter Almgren
  • Marketa Sjögren
  • Garrett Smith
  • Gunnar Engström
  • Bo Hedblad
  • Olle Melander

Summary, in English

OBJECTIVES: To evaluate the proportion of cardiovascular disease (CVD) incidence that is explained by genetic variation at chromosome 9p21 and to test whether such variation adds incremental information with regard to CVD prediction, beyond traditional risk factors. DESIGN, SETTING AND PARTICIPANTS: rs4977574 on chromosome 9p21 was genotyped in 24 777 subjects from the Malmö Diet and Cancer study who were free from CVD prior to the baseline examination. Association between genotype and incident CVD (n = 2668) during a median follow-up of 11.7 years was evaluated in multivariate Cox proportional hazard models. Analyses were performed in quartiles of baseline age, and linear trends in effect size across age groups were estimated in logistic regression models. RESULTS: In additive models, chromosome 9p21 significantly predicted CVD in the entire population (hazard ratio 1.17 per G allele, 95% confidence interval 1.11-1.23, P < 0.001). Effect estimates increased from the highest (Q4) to the lowest quartile (Q1) of baseline age, but this trend was not significant. The overall population attributable risk conferred by chromosome 9p21 in fully adjusted models was 13%, ranging from 17% in Q1 to 11% in Q4. Addition of chromosome 9p21 to traditional risk factors only marginally improved predictive accuracy. CONCLUSION: The high population attributable risk conferred by chromosome 9p21 suggests that future interventions interfering with downstream mechanisms of the genetic variation may affect CVD incidence over a broad range of ages. However, variation of chromosome 9p21 alone does not add clinically meaningful information in terms of CVD prediction beyond traditional risk factors at any age.

Department/s

  • Cardiovascular Research - Hypertension
  • Genomics, Diabetes and Endocrinology
  • Bioimplant Research
  • Cardiovascular Research - Epidemiology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2013

Language

English

Pages

233-240

Publication/Series

Journal of Internal Medicine

Volume

274

Issue

3

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Cardiovascular Research - Hypertension
  • Genomics, Diabetes and Endocrinology
  • Bioimplant Research
  • Cardiovascular Research - Epidemiology

ISBN/ISSN/Other

  • ISSN: 1365-2796