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Genetics of coronary artery disease in the light of genome-wide association studies

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Abstract

As clinicians, we understand the development of atherosclerosis as a consequence of cholesterol deposition and inflammation in the arterial wall, both being triggered by traditional risk factors such as hypertension, hyperlipidaemia or diabetes mellitus. Another risk factor is genetic predisposition, as indicated by the predictive value of a positive family history. However, we had to wait until recently to appreciate the abundant contribution of genetic variation to the manifestation of atherosclerosis. Indeed, by now 164 chromosomal loci have been identified by genome-wide association studies (GWAS) to affect the risk of coronary artery disease. By design, practically all risk variants discovered by GWAS are frequently found in our population, resulting in the fact that principally every Western European individual carries between 130 and 190 risk alleles at the known, genome-wide significant loci (there are 0, 1, or 2 risk alleles per locus). One can assume that it is this widespread disposition that makes mankind susceptible to the detrimental effects of lifestyle factors, which likewise increase the risk of atherosclerosis. In this review, we summarize the recent genetic discoveries and attempt to group the multiple genetic risk variants in functional groups that may become actionable from a preventive or therapeutic perspective.

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Abbreviations

CAD:

Coronary artery disease

GWAS:

Genome-wide association study/studies

MI:

Myocardial infarction

NO:

Nitric oxide

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Funding

This work was supported by grants from the Fondation Leducq [CADgenomics, 12CVD02], the German Federal Ministry of Education and Research (BMBF) within the framework of ERA-NET on Cardiovascular Disease, Joint Transnational Call 2017 [ERA-CVD: grant JTC2017_21-040], within the framework of target validation [BlockCAD: 16GW0198K], within the framework of the e:Med research and funding concept [AbCD-Net: grant 01ZX1706C and e:AtheroSysMed: grant 01ZX1313A-2014], and the European Union Seventh Framework Programme FP7/2007–2013, under grant agreement no. HEALTH-F2-2013-601456 (CVgenes-at-target). Further grants were received from the Deutsche Forschungsgemeinschaft (DFG) as part of the Sonderforschungsbereich CRC 1123 (B2).

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  1. Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität München, 80636, Munich, Germany

    Heribert Schunkert, Moritz von Scheidt, Thorsten Kessler, Barbara Stiller, Lingyao Zeng & Baiba Vilne

  2. DZHK (German Center for Cardiovascular Research) e.V., Partner Site Munich Heart Alliance, 80636, Munich, Germany

    Heribert Schunkert, Moritz von Scheidt, Thorsten Kessler, Lingyao Zeng & Baiba Vilne

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This article is part of the Spotlight Issue of Clinical Research in Cardiology with the title “German cardiac society welcomes ESC”.

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Schunkert, H., von Scheidt, M., Kessler, T. et al. Genetics of coronary artery disease in the light of genome-wide association studies. Clin Res Cardiol 107 (Suppl 2), 2–9 (2018). https://doi.org/10.1007/s00392-018-1324-1

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