Genome-wide analysis yields new loci associating with aortic valve stenosis

Aortic valve stenosis (AS) is the most common valvular heart disease, characterized by a thickened and calcified valve causing left ventricular outflow obstruction. Severe AS is a significant cause of morbidity and mortality, affecting approximately 5% of those over 70 years of age 1,2,3 . Little is known about the genetics of AS, although recently a variant at the LPA locus 4 and a rare MYH6 missense variant were found to associate with AS 5 . We report a large genome-wide association study (GWAS) with a follow-up in up to 7,307 AS cases and 801,073 controls. We identified two new AS loci, on chromosome 1p21 near PALMD (rs7543130; OR=1.20, P =1.2×10 −22 ) and on chromosome 2q22 in TEX41 (rs1830321; OR=1.15, P =1.8×10 −13 ). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR=1.28, P =6.6×10 −10 ) and aortic root diameter ( P =1.30×10 −8 ) and rs1830321 associates with BAV (OR=1.12, P =5.3×10 −3 and coronary artery disease (CAD) (OR=1.05, P=9.3×10 −5) . These results indicate that AS is partly rooted in the same processes as cardiac development and atherosclerosis.