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dc.contributor.authorKeramati, Ali R.
dc.contributor.authorChen, Ming Huei
dc.contributor.authorRodriguez, Benjamin A.T.
dc.contributor.authorYanek, Lisa R.
dc.contributor.authorBhan, Arunoday
dc.contributor.authorGaynor, Brady J.
dc.contributor.authorRyan, Kathleen
dc.contributor.authorBrody, Jennifer A.
dc.contributor.authorZhong, Xue
dc.contributor.authorWei, Qiang
dc.contributor.authorAbe, Namiko
dc.contributor.authorAbecasis, Goncalo
dc.contributor.authorAguet, Francois
dc.contributor.authorAlbert, Christine
dc.contributor.authorAlmasy, Laura
dc.contributor.authorAlonso, Alvaro
dc.contributor.authorAment, Seth
dc.contributor.authorAnderson, Peter
dc.contributor.authorAnugu, Pramod
dc.contributor.authorApplebaum-Bowden, Deborah
dc.contributor.authorArdlie, Kristin
dc.contributor.authorArking, Dan
dc.contributor.authorArnett, Donna K.
dc.contributor.authorAshley-Koch, Allison
dc.contributor.authorAslibekyan, Stella
dc.contributor.authorAssimes, Tim
dc.contributor.authorAuer, Paul
dc.contributor.authorAvramopoulos, Dimitrios
dc.contributor.authorAyas, Najib
dc.contributor.authorBalasubramanian, Adithya
dc.contributor.authorBarnard, John
dc.contributor.authorBarnes, Kathleen
dc.contributor.authorBarr, R. Graham
dc.contributor.authorBarron-Casella, Emily
dc.contributor.authorBarwick, Lucas
dc.contributor.authorBeaty, Terri
dc.contributor.authorBeck, Gerald
dc.contributor.authorBecker, Diane
dc.contributor.authorBecker, Lewis
dc.contributor.authorBeer, Rebecca
dc.contributor.authorBeitelshees, Amber
dc.contributor.authorBenjamin, Emelia
dc.contributor.authorBenos, Takis
dc.contributor.authorBezerra, Marcos
dc.contributor.authorBielak, Larry
dc.contributor.authorBis, Joshua
dc.contributor.authorBlackwell, Thomas
dc.contributor.authorBlangero, John
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorBowden, Donald W.
dc.contributor.authorBowler, Russell
dc.contributor.authorBrody, Jennifer
dc.contributor.authorBroeckel, Ulrich
dc.contributor.authorBroome, Jai
dc.contributor.authorBrown, Deborah
dc.contributor.authorBunting, Karen
dc.contributor.authorBurchard, Esteban
dc.contributor.authorBustamante, Carlos
dc.contributor.authorButh, Erin
dc.contributor.authorCade, Brian
dc.contributor.authorCardwell, Jonathan
dc.contributor.authorCarey, Vincent
dc.contributor.authorCarrier, Julie
dc.contributor.authorCarty, Cara
dc.contributor.authorCasaburi, Richard
dc.contributor.authorRomero, Juan P.Casas
dc.contributor.authorCasella, James
dc.contributor.authorCastaldi, Peter
dc.contributor.authorChaffin, Mark
dc.contributor.authorChang, Christy
dc.contributor.authorChang, Yi Cheng
dc.contributor.authorChasman, Daniel
dc.contributor.authorChavan, Sameer
dc.contributor.authorChen, Bo Juen
dc.contributor.authorChen, Wei Min
dc.contributor.authorChen, Yii Der Ida
dc.contributor.authorCho, Michael
dc.contributor.authorChoi, Seung Hoan
dc.contributor.authorChuang, Lee Ming
dc.contributor.authorChung, Mina
dc.contributor.authorChung, Ren Hua
dc.contributor.authorClish, Clary
dc.contributor.authorComhair, Suzy
dc.contributor.authorConomos, Matthew
dc.contributor.authorCornell, Elaine
dc.contributor.authorCorrea, Adolfo
dc.contributor.authorCrandall, Carolyn
dc.contributor.authorCrapo, James
dc.contributor.authorCupples, L. Adrienne
dc.contributor.authorCurran, Joanne
dc.contributor.authorCurtis, Jeffrey
dc.contributor.authorCuster, Brian
dc.contributor.authorDamcott, Coleen
dc.contributor.authorDarbar, Dawood
dc.contributor.authorDavid, Sean
dc.contributor.authorDavis, Colleen
dc.contributor.authorDaya, Michelle
dc.contributor.authorde Andrade, Mariza
dc.contributor.authorFuentes, Lisa de las
dc.contributor.authorde Vries, Paul
dc.date.accessioned2021-06-28T14:12:08Z
dc.date.available2021-06-28T14:12:08Z
dc.date.issued2021-06-15
dc.identifier.urihttp://hdl.handle.net/10713/16093
dc.description.abstractPlatelet aggregation at the site of atherosclerotic vascular injury is the underlying pathophysiology of myocardial infarction and stroke. To build upon prior GWAS, here we report on 16 loci identified through a whole genome sequencing (WGS) approach in 3,855 NHLBI Trans-Omics for Precision Medicine (TOPMed) participants deeply phenotyped for platelet aggregation. We identify the RGS18 locus, which encodes a myeloerythroid lineage-specific regulator of G-protein signaling that co-localizes with expression quantitative trait loci (eQTL) signatures for RGS18 expression in platelets. Gene-based approaches implicate the SVEP1 gene, a known contributor of coronary artery disease risk. Sentinel variants at RGS18 and PEAR1 are associated with thrombosis risk and increased gastrointestinal bleeding risk, respectively. Our WGS findings add to previously identified GWAS loci, provide insights regarding the mechanism(s) by which genetics may influence cardiovascular disease risk, and underscore the importance of rare variant and regulatory approaches to identifying loci contributing to complex phenotypes. © 2021, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.en_US
dc.description.sponsorshipNational Institutes of Healthen_US
dc.description.urihttps://doi.org/10.1038/s41467-021-23470-9en_US
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofNature Communicationsen_US
dc.subject.meshCardiovascular Diseases--geneticsen_US
dc.subject.meshGenetic Locien_US
dc.subject.meshHeart Disease Risk Factorsen_US
dc.subject.meshPlatelet Aggregation--geneticsen_US
dc.subject.meshWhole Genome Sequencingen_US
dc.titleGenome sequencing unveils a regulatory landscape of platelet reactivityen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41467-021-23470-9
dc.source.volume12
dc.source.issue1


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