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dc.contributor.authorSarnowski, Chloé
dc.contributor.authorChen, Han
dc.contributor.authorBiggs, Mary L
dc.contributor.authorWassertheil-Smoller, Sylvia
dc.contributor.authorBressler, Jan
dc.contributor.authorIrvin, Marguerite R
dc.contributor.authorRyan, Kathleen A
dc.contributor.authorKarasik, David
dc.contributor.authorArnett, Donna K
dc.contributor.authorCupples, L Adrienne
dc.contributor.authorFardo, David W
dc.contributor.authorGogarten, Stephanie M
dc.contributor.authorHeavner, Benjamin D
dc.contributor.authorJain, Deepti
dc.contributor.authorKang, Hyun Min
dc.contributor.authorKooperberg, Charles
dc.contributor.authorMainous, Arch G
dc.contributor.authorMitchell, Braxton D
dc.contributor.authorMorrison, Alanna C
dc.contributor.authorO'Connell, Jeffrey R
dc.contributor.authorPsaty, Bruce M
dc.contributor.authorRice, Kenneth
dc.contributor.authorSmith, Albert V
dc.contributor.authorVasan, Ramachandran S
dc.contributor.authorWindham, B Gwen
dc.contributor.authorKiel, Douglas P
dc.contributor.authorMurabito, Joanne M
dc.contributor.authorLunetta, Kathryn L
dc.date.accessioned2021-07-06T14:14:22Z
dc.date.available2021-07-06T14:14:22Z
dc.date.issued2021-07-02
dc.identifier.urihttp://hdl.handle.net/10713/16135
dc.description.abstractHandgrip strength is a widely used measure of muscle strength and a predictor of a range of morbidities including cardiovascular diseases and all-cause mortality. Previous genome-wide association studies of handgrip strength have focused on common variants primarily in persons of European descent. We aimed to identify rare and ancestry-specific genetic variants associated with handgrip strength by conducting whole-genome sequence association analyses using 13,552 participants from six studies representing diverse population groups from the Trans-Omics in Precision Medicine (TOPMed) Program. By leveraging multiple handgrip strength measures performed in study participants over time, we increased our effective sample size by 7-12%. Single-variant analyses identified ten handgrip strength loci among African-Americans: four rare variants, five low-frequency variants, and one common variant. One significant and four suggestive genes were identified associated with handgrip strength when aggregating rare and functional variants; all associations were ancestry-specific. We additionally leveraged the different ancestries available in the UK Biobank to further explore the ancestry-specific association signals from the single-variant association analyses. In conclusion, our study identified 11 new loci associated with handgrip strength with rare and/or ancestry-specific genetic variations, highlighting the added value of whole-genome sequencing in diverse samples. Several of the associations identified using single-variant or aggregate analyses lie in genes with a function relevant to the brain or muscle or were reported to be associated with muscle or age-related traits. Further studies in samples with sequence data and diverse ancestries are needed to confirm these findings.en_US
dc.description.urihttps://doi.org/10.1371/journal.pone.0253611en_US
dc.language.isoenen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.ispartofPLoS ONEen_US
dc.subject.meshGenetic Locien_US
dc.subject.meshGenetic Variationen_US
dc.subject.meshHand Strengthen_US
dc.subject.meshWhole Genome Sequencingen_US
dc.titleIdentification of novel and rare variants associated with handgrip strength using whole genome sequence data from the NHLBI Trans-Omics in Precision Medicine (TOPMed) Program.en_US
dc.typeArticleen_US
dc.identifier.doi10.1371/journal.pone.0253611
dc.identifier.pmid34214102
dc.source.journaltitlePloS one
dc.source.volume16
dc.source.issue7
dc.source.beginpagee0253611
dc.source.endpage
dc.source.countryUnited States


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