Helgadottir, AnnaThorleifsson, GudmarGretarsdottir, SolveigStefansson, Olafur A.Tragante, ViniciusThorolfsdottir, Rosa B.Jonsdottir, IngileifBjornsson, ThorsteinnSteinthorsdottir, ValgerdurVerweij, NiekNielsen, Jonas B.Zhou, WeiFolkersen, LasseMartinsson, AndreasHeydarpour, MahyarPrakash, SiddharthOskarsson, GylfiGudbjartsson, TomasGeirsson, ArnarOlafsson, IsleifurSigurdsson, Emil L.Almgren, PeterMelander, OlleFranco-Cereceda, AndersHamsten, AndersFritsche, LarsLin, MaoxuanYang, BoHornsby, WhitneyGuo, DongchuanBrummett, Chad M.Abecasis, GonçaloMathis, MichaelMilewicz, DiannaBody, SimonEriksson, PerWiller, Cristen J.Hveem, KristianNewton-Cheh, ChristopherSmith, J. GustavDanielsen, RagnarThorgeirsson, GudmundurThorsteinsdottir, UnnurGudbjartsson, Daniel F.Holm, HilmaStefansson, Kari2018-04-192018Helgadottir, A., G. Thorleifsson, S. Gretarsdottir, O. A. Stefansson, V. Tragante, R. B. Thorolfsdottir, I. Jonsdottir, et al. 2018. “Genome-wide analysis yields new loci associating with aortic valve stenosis.” Nature Communications 9 (1): 987. doi:10.1038/s41467-018-03252-6. http://dx.doi.org/10.1038/s41467-018-03252-6.http://nrs.harvard.edu/urn-3:HUL.InstRepos:35982008Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (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 (OR = 1.05, P = 9.3 × 10−5). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.en-USJournal Article2018-04-1910.1038/s41467-018-03252-6