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Recent genomic studies have identified a locus near the gene <jats:italic>PALMD<\/jats:italic> (palmdelphin) strongly associated with CAVS. Here, we show that genetically-determined expression of <jats:italic>PALMD<\/jats:italic> in the aortic valve is inversely associated with CAVS, with a stronger effect in women, in a meta-analysis of two large cohorts totaling 2359 cases and 350,060 controls. We further demonstrate the specificity of this relationship by showing the absence of other significant association between the genetically-determined expression of <jats:italic>PALMD<\/jats:italic> in 9 tissues and 852 phenotypes. Using genome-wide association studies meta-analyses of cardiovascular traits, we identify a significant colocalized positive association between genetically-determined expression of <jats:italic>PALMD<\/jats:italic> in four non-cardiac tissues (brain anterior cingulate cortex, esophagus muscularis, tibial nerve and subcutaneous adipose tissue) and atrial fibrillation. The present work further establishes <jats:italic>PALMD<\/jats:italic> as a promising molecular target for CAVS.<\/jats:p>","DOI":"10.1038\/s42003-020-01210-x","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T10:09:48Z","timestamp":1598609388000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Phenome-wide analyses establish a specific association between aortic valve PALMD expression and calcific aortic valve stenosis"],"prefix":"10.1038","volume":"3","author":[{"given":"Zhonglin","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5351-596X","authenticated-orcid":false,"given":"Nathalie","family":"Gaudreault","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benoit J.","family":"Arsenault","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3805-2004","authenticated-orcid":false,"given":"Patrick","family":"Mathieu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3067-3711","authenticated-orcid":false,"given":"Yohan","family":"Boss\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1893-8307","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Th\u00e9riault","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,8,28]]},"reference":[{"key":"1210_CR1","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1016\/0735-1097(93)90249-Z","volume":"21","author":"M Lindroos","year":"1993","unstructured":"Lindroos, M., Kupari, M., Heikkila, J. & Tilvis, R. 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