To yield further insights into the aetiology of cardiovascular diseases, such as myocardial infarction and stroke, the CEU leads efforts to identify novel genetic risk factors for these diseases. As of 2016, the CEU has provided leadership for the discovery of ~20 coronary disease loci through establishment of the CHD Exome+ Consortium, and has contributed to discovery of a further ~25 coronary disease loci through involvement in the CARDIoGRAMplusC4D Consortium (Nat Genet 2015;47:1121-30; Nat Genet 2013;45:25-33 ) and C4D Consortium. Increasingly we have begun exploring rare variants, helping to discover rare alleles in several genes that causally implicated triglyceride(TG)-rich lipoproteins in coronary disease (Stitziel, NEJM 2016;374:1134-44, Do, Nature 2015;518:102-6).
We are continuing this work in four main ways:
- Co-leadership of the CARDIoGRAMplusC4D 1M+ Heart project, a global consortium of imputed genotype array data involving >250,000 coronary disease cases and >1 million controls
- Sequencing studies of multi-ethnic early-onset myocardial infarction cases with Dr Sekar Kathiresan at the Broad Institute. Within this global consortium of >25,000 cases and >25,000 controls will be participants from our studies in Bangladesh (BRAVE), Malaysia (MAVERIK ) and Pakistan (PROMIS ).
- Study of mitochondrial DNA parameters and coronary disease using array data and sequencing data from our CHD Exome+ Consortium, the INTERVAL bioresource and UK Biobank. Since mtDNA has previously been understudied, there may be potential to identify novel causal CVD risk factors through study of germ-line variants, heteroplasmy or mtDNA levels, in collaboration with Profs. Patrick Chinnery and Nicole Soranzo
- Through the EPIC-CVD study, which includes >8000 incident stroke cases, the CEU is a key collaborator in the global MEGASTROKE consortium, a meta-analysis of imputed array-based data for stroke subtypes (~64,000 cases, ~457,000 controls).