Identification of novel and rare variants associated with handgrip strength using whole genome sequence data from the NHLBI Trans-Omics in Precision Medicine (TOPMed) Program.

Handgrip 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. W...

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Autores principales:	Chloé Sarnowski, Han Chen, Mary L Biggs, Sylvia Wassertheil-Smoller, Jan Bressler, Marguerite R Irvin, Kathleen A Ryan, David Karasik, Donna K Arnett, L Adrienne Cupples, David W Fardo, Stephanie M Gogarten, Benjamin D Heavner, Deepti Jain, Hyun Min Kang, Charles Kooperberg, Arch G Mainous, Braxton D Mitchell, Alanna C Morrison, Jeffrey R O'Connell, Bruce M Psaty, Kenneth Rice, Albert V Smith, Ramachandran S Vasan, B Gwen Windham, Douglas P Kiel, Joanne M Murabito, Kathryn L Lunetta, TOPMed Longevity and Healthy Aging Working Group, from the NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c6f9d153af14487282b1e003198122ed
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spelling	oai:doaj.org-article:c6f9d153af14487282b1e003198122ed2021-12-02T20:15:40ZIdentification of novel and rare variants associated with handgrip strength using whole genome sequence data from the NHLBI Trans-Omics in Precision Medicine (TOPMed) Program.1932-620310.1371/journal.pone.0253611https://doaj.org/article/c6f9d153af14487282b1e003198122ed2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253611https://doaj.org/toc/1932-6203Handgrip 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.Chloé SarnowskiHan ChenMary L BiggsSylvia Wassertheil-SmollerJan BresslerMarguerite R IrvinKathleen A RyanDavid KarasikDonna K ArnettL Adrienne CupplesDavid W FardoStephanie M GogartenBenjamin D HeavnerDeepti JainHyun Min KangCharles KooperbergArch G MainousBraxton D MitchellAlanna C MorrisonJeffrey R O'ConnellBruce M PsatyKenneth RiceAlbert V SmithRamachandran S VasanB Gwen WindhamDouglas P KielJoanne M MurabitoKathryn L LunettaTOPMed Longevity and Healthy Aging Working Groupfrom the NHLBI Trans-Omics for Precision Medicine (TOPMed) ConsortiumPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0253611 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chloé Sarnowski Han Chen Mary L Biggs Sylvia Wassertheil-Smoller Jan Bressler Marguerite R Irvin Kathleen A Ryan David Karasik Donna K Arnett L Adrienne Cupples David W Fardo Stephanie M Gogarten Benjamin D Heavner Deepti Jain Hyun Min Kang Charles Kooperberg Arch G Mainous Braxton D Mitchell Alanna C Morrison Jeffrey R O'Connell Bruce M Psaty Kenneth Rice Albert V Smith Ramachandran S Vasan B Gwen Windham Douglas P Kiel Joanne M Murabito Kathryn L Lunetta TOPMed Longevity and Healthy Aging Working Group from the NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium Identification of novel and rare variants associated with handgrip strength using whole genome sequence data from the NHLBI Trans-Omics in Precision Medicine (TOPMed) Program.
description	Handgrip 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.
format	article
author	Chloé Sarnowski Han Chen Mary L Biggs Sylvia Wassertheil-Smoller Jan Bressler Marguerite R Irvin Kathleen A Ryan David Karasik Donna K Arnett L Adrienne Cupples David W Fardo Stephanie M Gogarten Benjamin D Heavner Deepti Jain Hyun Min Kang Charles Kooperberg Arch G Mainous Braxton D Mitchell Alanna C Morrison Jeffrey R O'Connell Bruce M Psaty Kenneth Rice Albert V Smith Ramachandran S Vasan B Gwen Windham Douglas P Kiel Joanne M Murabito Kathryn L Lunetta TOPMed Longevity and Healthy Aging Working Group from the NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
author_facet	Chloé Sarnowski Han Chen Mary L Biggs Sylvia Wassertheil-Smoller Jan Bressler Marguerite R Irvin Kathleen A Ryan David Karasik Donna K Arnett L Adrienne Cupples David W Fardo Stephanie M Gogarten Benjamin D Heavner Deepti Jain Hyun Min Kang Charles Kooperberg Arch G Mainous Braxton D Mitchell Alanna C Morrison Jeffrey R O'Connell Bruce M Psaty Kenneth Rice Albert V Smith Ramachandran S Vasan B Gwen Windham Douglas P Kiel Joanne M Murabito Kathryn L Lunetta TOPMed Longevity and Healthy Aging Working Group from the NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
author_sort	Chloé Sarnowski
title	Identification of novel and rare variants associated with handgrip strength using whole genome sequence data from the NHLBI Trans-Omics in Precision Medicine (TOPMed) Program.
title_short	Identification of novel and rare variants associated with handgrip strength using whole genome sequence data from the NHLBI Trans-Omics in Precision Medicine (TOPMed) Program.
title_full	Identification of novel and rare variants associated with handgrip strength using whole genome sequence data from the NHLBI Trans-Omics in Precision Medicine (TOPMed) Program.
title_fullStr	Identification of novel and rare variants associated with handgrip strength using whole genome sequence data from the NHLBI Trans-Omics in Precision Medicine (TOPMed) Program.
title_full_unstemmed	Identification of novel and rare variants associated with handgrip strength using whole genome sequence data from the NHLBI Trans-Omics in Precision Medicine (TOPMed) Program.
title_sort	identification of novel and rare variants associated with handgrip strength using whole genome sequence data from the nhlbi trans-omics in precision medicine (topmed) program.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/c6f9d153af14487282b1e003198122ed
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Identification of novel and rare variants associated with handgrip strength using whole genome sequence data from the NHLBI Trans-Omics in Precision Medicine (TOPMed) Program.

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