IUMSP Institut universitaire de médecine sociale et préventive, Lausanne Exploring the association of the CYP1A1- CYP1A2 locus with blood pressure in CoLaus Diana Marek and Murielle Bochud

IUMSP Institut universitaire de médecine sociale et préventive, Lausanne 2 Background information  High blood pressure leads to hypertension, a major modifiable cardiovascular risk factor.  In Switzerland, hypertension affects 1 in 3 adults.  Hypertension increases the risk of stroke, myocardial infarction and kidney diseases.  So far, the exact biological mechanism underlying hypertension is unknown in 95% of cases.  Hypertension aggregates in families, which suggests that genes play a role.  Genetic association studies are used to identify new blood pressure candidate genes.

IUMSP Institut universitaire de médecine sociale et préventive, Lausanne 3 New loci associated with blood pressure (International Consortium on blood pressure genetics) Ehret et al, Nature 2011, September 11 Genome-wide meta-analysis for systolic and diastolic blood pressure Chromosomes Significance of the statistical association 29 genetic variants identified Includes data from the CoLaus study in Lausanne

IUMSP Institut universitaire de médecine sociale et préventive, Lausanne 4 29 SNPs genome-wide significant in 28 loci 8/29 SNPs are in high LD (r 2 > 0.8) with a non-synonymous coding SNP. Some evidence that the 29 SNPs are enriched for eSNPs. The phenotypic variance explained by the 29 variants is ~1%.

IUMSP Institut universitaire de médecine sociale et préventive, Lausanne 5 Locus 1: association signal with blood pressure at a locus where the causal gene is NOT clear Ehret et al, Nature 2011

IUMSP Institut universitaire de médecine sociale et préventive, Lausanne 6 Locus 2: the causal gene is NOT clear as well

IUMSP Institut universitaire de médecine sociale et préventive, Lausanne 7 Aims of this project  to analyze the association of two ICBP loci (rs and rs ) with systolic and diastolic blood pressure in CoLaus.  to search the literature on the CYP1A1, CYP1A2 and CSK genes and to choose the most likely causal gene for the rs locus.  to search the literature on the CYP17A1, C10orf32, AS3MT, CNNM2 genes and choose the most likely gene for the.rs locus.  to conduct stratified analyses by selected covariates (the choice of covariates needs to be decided by the group) to confirm the most likely causal gene.