Genetics of coronary disease

Abstract

Coronary artery disease (CAD), including its severe form, myocardial infarction (MI), is a common serious disorder, and a leading cause of death in industrial countries. The pathogenesis depends on multiple interactions on an environmental and genetic basis. As genetic heritability of CAD comprises ~ 50% of the pathogenesis, elucidating the detailed genetic architecture of CAD would facilitate development of a future precision medicine. Initially, we started a genome-wide association study (GWAS) for MI with about 100,000 single nucleotide polymorphisms (SNP) in Japanese from early 2000, and identified the SNPs in lymphotoxin-α gene (LTA) associated with the increased risk of MI. As far as we know, this study is the first GWAS for common disease worldwide. This hypothesis-free GWAS ultimately led to identification of a possible MI pathological condition by mediating an inflammatory cascade including IKK signalosome and BRAP, encoded by the gene that was robustly associated with an increased risk of MI in Asian population. On the other hand, recent mega-GWASs for more than 200 traits have collectively revealed many genetic risk factors for common diseases. To date, GWASs from around the world have shown 98 genetic risk factors for CAD.