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Genome-Wide Association Meta-Analysis Supports Genes Involved in Valve and Cardiac Development to Associate With Mitral Valve Prolapse

dc.rights.licenseopenen_US
dc.contributor.authorYU, Mengyao
dc.contributor.authorKYRYACHENKO, Sergiy
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.contributor.authorAMOUYEL, Philippe
dc.contributor.authorSCHOTT, Jean Jacques
dc.contributor.authorLE TOURNEAU, Thierry
dc.contributor.authorDINA, Christian
dc.contributor.authorNORRIS, Russell A.
dc.contributor.authorHAGEGE, Albert A.
dc.contributor.authorJEUNEMAITRE, Xavier
dc.contributor.authorBOUATIA-NAJI, Nabila
dc.date.accessioned2021-11-08T15:29:48Z
dc.date.available2021-11-08T15:29:48Z
dc.date.issued2021-08-31
dc.identifier.issn2574-8300 (Electronic) 2574-8300 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/123784
dc.description.abstractEnBACKGROUND: Mitral valve prolapse (MVP) is a common cardiac valve disease, which affects 1 in 40 in the general population. Previous genome-wide association study have identified 6 risk loci for MVP. But these loci explained only partially the genetic risk for MVP. We aim to identify additional risk loci for MVP by adding data set from the UK Biobank. METHODS: We reanalyzed 1007/479 cases from the MVP-France study, 1469/862 controls from the MVP-Nantes study for reimputation genotypes using HRC and TOPMed panels. We also incorporated 434 MVP cases and 4527 controls from the UK Biobank for discovery analyses. Genetic association was conducted using SNPTEST and meta-analyses using METAL. We used FUMA for post-genome-wide association study annotations and MAGMA for gene-based and gene-set analyses. RESULTS: We found TOPMed imputation to perform better in terms of accuracy in the lower ranges of minor allele frequency below 0.1. Our updated meta-analysis included UK Biobank study for ≈8 million common single-nucleotide polymorphisms (minor allele frequency >0.01) and replicated the association on Chr2 as the top association signal near TNS1. We identified an additional risk locus on Chr1 (SYT2) and 2 suggestive risk loci on chr8 (MSRA) and chr19 (FBXO46), all driven by common variants. Gene-based association using MAGMA revealed 6 risk genes for MVP with pronounced expression levels in cardiovascular tissues, especially the heart and globally part of enriched GO terms related to cardiac development. CONCLUSIONS: We report an updated meta-analysis genome-wide association study for MVP using dense imputation coverage and an improved case-control sample. We describe several loci and genes with MVP spanning biological mechanisms highly relevant to MVP, especially during valve and heart development.
dc.language.isoENen_US
dc.subject.enHeart valve diseases
dc.subject.enMitral valve prolapse
dc.subject.enAssociation
dc.subject.enMeta-analysis
dc.subject.enComputational biology
dc.title.enGenome-Wide Association Meta-Analysis Supports Genes Involved in Valve and Cardiac Development to Associate With Mitral Valve Prolapse
dc.typeArticle de revueen_US
dc.identifier.doi10.1161/CIRCGEN.120.003148en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed34461747en_US
bordeaux.journalCirculation-Genomic and Precision Medicineen_US
bordeaux.pageCIRCGEN120003148en_US
bordeaux.volume14en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue5en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamVINTAGEen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03419733
hal.version1
hal.date.transferred2021-11-08T15:29:54Z
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
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