The PROCARDIS study is a case-control study of coronary heart disease (CHD), involving 5000 cases and 5000 controls, designed to investigate genetic susceptibility to CHD. It is a collaborative study between CTSU and the Radcliffe Department of Medicine (University of Oxford) and universities in Sweden, Germany and Italy.
We discovered two LPA SNPs (rs10455872 and rs3798220) that encode lipoprotein (a) levels and small apo(a) isoform size that are strongly associated with CHD. A meta-analysis of 8000 CHD cases found an odds ratio of 1.51 (95% CI: 1.38-1.66) for one variant and 2.57 (1.80-3.67) for two variants, which provided strong support for the role of Lp(a) as a therapeutic target for prevention of CHD. The PROCARDIS data were combined with other similar studies in CARDIoGRAMplusC4D consortium, involving 61,000 CHD cases and 123,000 controls, to investigate the genetic architecture of CHD. Using imputation with 1000 Genomes data, we examined associations of CHD with 38,000 variants and confirmed associations with 48 significant loci. Our results concluded that the genetic susceptibility to CHD is largely determined by common variants of small effect size.
We are currently assessing the relevance of inflammatory cytokines for risk of CHD to understand the role of inflammation in CHD. We are also studying the role of oxidised phospholipids carried on Lp(a) and oxidised phospholipids carried on plasminogen for risk of CHD to understand the mechanisms by which elevated levels of Lp(a) cause CHD.