GWAS on Calcific Aortic Valve Stenosis in Quebec (QUEBEC-CAVS)

Calcific aortic valve stenosis (CAVS) is a common and life-threatening heart disease with no drug that can stop or delay its progression. A genome-wide association study (GWAS) on 1,009 cases and 1,017 ethnically-matched controls was performed to identify susceptibility genes for CAVS. ]]>
A genome-wide association study (GWAS) on 1,009 cases and 1,017 ethnically-matched controls was performed to identify susceptibility genes for calcific aortic valve stenosis (CAVS). All cases and controls were collected from a single institution located in Quebec City, Canada. Genotyping was performed using the Illumina HumanOmniExpress BeadChip and the data was imputed using the HRC.r1-1 set. Genetic association tests were performed using additive logistic regression models based on expected genotype counts (dosages) as implemented in the software SNPTEST v2.5.2, adjusting for age, sex, and the first ten ancestry-based principal components. The 1000 Genome data set from dbSNP was used to annotate and display the association results in the dbGaP genome browser. Inclusion - Cases: Patients with severe tricuspid nonrheumatic CAVS undergoing aortic valve replacement. European descent. Inclusion - Controls: Absence of CAVS confirmed by echocardiography. Matched in a 1:1 ratio with cases for age, gender, type 2 diabetes and hypertension. European descent. Exclusion - Cases: Severe regurgitation or other severe valvular heart diseases. Exclusion - Controls: Patients with a history of severe valvular heart disease (at any of the 4 valves), with significant aortic valve regurgitation (grade > 2) or with end stage renal disease (eGFR < 15 mL/min/1.73m2). ]]>
We have previously performed a GWAS on CAVS (Guauque-Olarte et al. Circ Cardiovasc Genet, 2015). This GWAS was completed with nearly 500 cases that are also part of the current analysis. Corresponding controls for this previous GWAS were taken from dbGaP. Accordingly, there is no overlap with controls use in this study.]]>