Genetic determinants of coronary artery calcification progression in the Heinz Nixdorf Recall Study: A Genome-wide association study

• Applicant: Dr. Sonali Pechlivanis, Ph.D.
• Subject Area: Epidemiology and Medical Biometry/Statistics
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 278740940

Atherosclerosis is the primary cause of coronary artery disease (CAD) and precedes the onset of most cases of clinically apparent coronary heart disease (CHD) by decades. Coronary artery calcification (CAC) is one of the most sensitive and specific markers of coronary atherosclerotic. The heritability of CAC progression has been reported to be strong, accounting for around 40% of the observed variance with 14% of variation explained by genetic factors. However, the genetic factors that are associated with progression of CAC are almost unknown. The importance of genome-wide association study (GWAS) is highlighted by its success to identify and reproduce genetic loci associated with various diseases. In this study we propose to carry out a GWAS approach in 3,481 Heinz Nixdorf Recall participants to find genetic variants associated with progression of CAC. We will adopt a two-stage strategy (a) discovery phase and (b) validation phase. In the discovery phase we will screen 3,481 Heinz Nixdorf Recall participants using latest genotyping chips to find signals associated with progression of CAC during a 5-year follow-up period. In the validation phase we will validate the top significant signals (up to 1000 markers selected based on P-values) in independent samples from NELSON Study. The proposed study will help to identify and validate genetic variants affecting progression of CAC which may help explain the essential mechanisms leading to CAD and might aid development of strategies to prevent, predict and treat CAD.

• DFG Programme: Research Grants
• International Connection: Netherlands
• Cooperation Partner: Professor Dr. Paul de Bakker