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Promises and perils of genome-wide association studies in coronary artery disease

Basic Science

Recently an enormous amount of information has become available with regard to the genetic background of coronary artery disease. Especially genome-wide association studies (GWAS) have contributed to this. This technique, where per patient in general > 500,000 genetic markers are checked, does lead to new clues, but does this GWAS technique answer (all) questions or does it mainly lead to confusion?

These questions were essential in this interesting ESC session called ‘promises and perils of genome-wide association studies in coronary artery disease’.

One should realize that in common complex diseases like CAD, genetic information can often explain <10% of the disease, but we do know that in twins, for example, around 30-50% of these CAD traits seem heritable. Where is the ‘missing heritability’? The first speaker (H. Snieder, Groningen, NL) did emphasize in this regard the complex gene-environment interaction, using blood pressure as an example. Factors like (mental and physical) stress, age and night/day differences already interact with genes. ‘No wonder we have difficulty in finding the rights genes for complex diseases’! Subsequently, A Pfeufer (Munchen, DE) highlighted the implications of GWAS.

Currently, GWAS are suitable for providing new insights in CAD, but putting the data in an appropriate predictive model is still challenging. This was also highlighted by N. Samani (Leicester, GB), where he also showed that the newly found genetic variants very often are in pathways that have nothing to do with common known risk factors for CAD and that in addition, some loci affect other disease phenotypes as well (pleiotropy).

The session was ended (by R. Clarke, Oxford, UK) with a very specific example, i.e. variants in the LPA gene, showing the value of GWAS, and he beautifully elucidated, by combining GWAS and plasma data, that very probably Lp(a) has a causal role in the development of CAD and therefore may be a suitable therapeutic target. In conclusion, considerable progress in genetic research is being made, especially by GWAS analyses in combination with gene-environment interaction research. This is leading to a better understanding of CAD and may provide new therapeutic targets. Making and applying appropriate predictive model s (partially) based on GWAS results is, however, currently still challenging.




Promises and perils of genome-wide association studies in coronary artery disease
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.