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Interplay of genetic, nutrient and lifestyle factors on incidence of coronary disease: EPIC-Heart

Final Report Summary - EPICHEART (Interplay of genetic, nutrient and lifestyle factors on incidence of coronary disease: EPIC-Heart)

Coronary heart disease (CHD) - the single leading cause of death in Europe - is jointly determined by genetic and lifestyle factors. It is unknown, however, how diet, nutrients, and lifestyle factors modulate genetic susceptibility. For scientific and public health reasons, there is a strategic need to study such interactions reliably.

The EPIC-Heart study built on work already conducted to identify ~12k incident CHD cases with detailed assessment of diet and lifestyle factors from 520k participants in a pan-European
prospective study. Lipid and other biomarker measurements had been made for these 12k cases and 15k referents from a random sub-cohort. The ERC-funded component of this project successfully assayed: >700k genetic variants in 12,000 incident CHD cases and 15,000 referents; 37 fatty acids in 12,000 incident CHD cases and; vitamin D metabolites in 12,000 incident CHD cases and 15,000 referents.

Significant added value was brought to this project, with supplementary funding enablingr: assay of 37 fatty acids in 15,000 referents from EPIC-InterAct and in 10,000 incident stroke cases from EPIC-CVD (FP7 grant agreement 279233); expansion of vitamin D assays to include vitamin C and a panel of 6 carotenoids from EPIC-CVD; assay of vitamins and carotenoids in 12,000 type 2 diabetes cases and 10,000 stroke cases from EPIC-CVD; genotyping of >200,000 SNPs in an additional 23,000 samples using the customised Metabochip; genotyping of ~450,000 low-frequency and rare genetic variants in 27,000 participants from EPIC-Heart and a further 73,0000 participants using the same array for comparison; genotyping of ~500,000 genomewide variants in 27,000 participants from EPIC-Heart; DNA extraction from 27,000 samples from the BHF/MRC funded EPIC-Heart project; sample retrieval for 12,000 incident CHD cases and 15,000 referents from the EPIC-Heart project.

Analyses of the EPIC-Heart study have included observational epidemiological studies (ie, the associations of lifestyle factors and blood biomarkers with incident cardiovascular outcomes), genetic discovery studies (ie, the association of genetic variants with risk of cardiovascular diseases and candidate biomarkers), causal evaluation (ie, Mendelian randomisation studies integrating genetic, biochemical and clinical data to identify causal biomarkers of disease) and methodological studies (ie, identifying novel analytical strategies to handle studies and data of the type in this project). In addition to the anticipated focus on vitamins, carotenoids and plasma fatty acids, the dataset funded by this grant has enabled the study of a diverse range of cardiovascular risk factors, including obesity, parity and breastfeeding, blood pressure and multimorbidity, as well as candidate causal pathways, such as the interleukin-1 receptor and lipoprotein-associated phospholipase A2 pathways. As of July 2017, nine publications are in print, with a further two dozen likely to emerge in the next few years. In summary, this world-leading study has enhanced Europe’s strengths in public health, nutrition and genetic epidemiology, and created a valuable future resource.