Daily Digest

To elucidate the genetics of coronary artery disease (CAD) in the Japanese population, researchers conducted a large-scale genome-wide association study of 168,228 individuals of Japanese ancestry (25,892 cases and 142,336 controls) with genotype imputation using a newly developed reference panel of Japanese haplotypes including 1,781 CAD cases and 2,636 controls. They detected eight new susceptibility loci and Japanese-specific rare variants contributing to disease severity and increased cardiovascular mortality. They then conducted a trans-ancestry meta-analysis and discovered 35 additional new loci. Using the meta-analysis results, they derived a polygenic risk score (PRS) for CAD, which outperformed those derived from either Japanese or European genome-wide association studies. Researchers manually curated a set of 255 splice events detected in a large-scale tissue-based proteomics experiment and found that more than a third had evidence of significant tissue-specific differences.