Most comprehensive genetic study for CAD in 185,000 cases and controls revealed novel insights in disease pathology

Members of the IIEG together with colleagues from the CARDIoGRAMplusC4D consortium published the most comprehensive genetic study for CAD. Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185,000 CAD cases and controls, interrogating 6.7 million common as well as 2.7 million low frequency variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. Moreover, we observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size. Furthermore, we report that only 20% of loci are related to known cardiovascular risk factors. This work has been published in Nature Genetics online ahead of print on September 7th, 2015. A Comprehensive 1000 Genomes-based GWAS meta-analysis of Coronary Artery Disease

A circular Manhattan plot summarizing the 1000 Genomes Project CAD association results.

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