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Exploring the association of the CYP1A1CYP1A2 locus with blood pressure in
CoLaus
Diana Marek and Murielle Bochud
IUMSP
Institut universitaire de médecine sociale et préventive, Lausanne
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
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New loci associated with blood pressure
(International Consortium on blood pressure genetics)
Significance of the
statistical association
29 genetic variants identified
Chromosomes
Includes data from the CoLaus study in Lausanne
Ehret et al, Nature 2011, September 11
Genome-wide meta-analysis for systolic and diastolic blood pressure
IUMSP
Institut universitaire de médecine sociale et préventive, Lausanne
3
29 SNPs genome-wide significant in 28 loci
8/29 SNPs are in high
LD (r2 > 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
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Locus 1: association signal with blood pressure at a
locus where the causal gene is NOT clear
Ehret et al, Nature 2011
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IUMSP
Institut universitaire de médecine sociale et préventive, Lausanne
Locus 2: the causal gene is NOT clear as well
IUMSP
Institut universitaire de médecine sociale et préventive, Lausanne
6
Aims of this project
 to analyze the association of two ICBP loci (rs1378942 and
rs11191548) 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
rs1378942 locus.
 to search the literature on the CYP17A1, C10orf32, AS3MT,
CNNM2 genes and choose the most likely gene for the
.rs11191548 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.
IUMSP
Institut universitaire de médecine sociale et préventive, Lausanne
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