Transfer - 50 K Vascular Disease SNP Array

Coordinator:    Prof. Dr. Wolfgang Koenig
Institution: Universität Ulm
The goal of project E2 was the analysis of the association between genetic variants and inflammatory markers, as well as their impact on cardio-metabolic disorders.
Genotyping was performed using two different platforms: on the one hand, the IBC Chip was used to genotype the entire KORA case-cohort study with the endpoints incident MI (N=2,600) as well as 700 additional deaths from MONICA/KORA and about 400 newly validated incident strokes; on the other hand, genotypes of MONICA/KORA S3 participants were determined in a genome-wide approach using the Affymetrix 500K chip.
Statistical analyses of approximately 20 intermediate inflammatory phenotypes, including C reactive protein (CRP), oxLDL and sE-selectin, were performed in collaboration with multiple studies and partners (such as LURIC, GHS, MORGAM, the CRP Coronary Heart Disease Genetics Collaboration, and the ERFC Consortium, etc.). Results indicate that, for example, CRP concentration is unlikely to represent a causal factor in coronary heart disease development. On the other hand, a meta-analysis of the ERFC consortium was able to show that IL-6 very likely is part of the causal chain of atherogenesis.
As part of the CARe consortium, additional phenotypes were analyzed. These analyses identified new loci for lipid traits such as HDL and LDL, type 2 diabetes, blood pressure and anthropometric measures like height and BMI.
Using the genome-wide data from the MONICA/KORA S3 survey, analyses were performed for multiple circulating biomarkers and were in part included in meta-analyses of the CHARGE consortium. These phenotypes amongst others were: fibrinogen, factor VII/VIII/vWF, d-dimers, PAI-1, Fibrinogen, SAA, CRP, IL-6, and Lp-PLA2. New gene loci were identified for factor VII, factor VIII, and von Willebrand factor outside previously known biological pathways, potentially pointing to novel prevention and treatment targets of atherothrombotic/hemostatic disorders. Analysis of fibrinogen highlights biological pathways that may be important in the regulation of inflammation associated with cardiovascular disease.
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