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Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women

Author

Listed:
  • Garan Jones

    (University of Exeter Medical School)

  • Katerina Trajanoska

    (Erasmus Medical Center
    Erasmus Medical Center)

  • Adam J. Santanasto

    (University of Pittsburgh, Department of Epidemiology)

  • Najada Stringa

    (Amsterdam UMC- Vrije Universiteit, Amsterdam Public Health Research Institute)

  • Chia-Ling Kuo

    (Biostatistics Center, Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health)

  • Janice L. Atkins

    (University of Exeter Medical School)

  • Joshua R. Lewis

    (Edith Cowan University
    School fo Public Health University of Sydney
    Medical School, University of Western Australia)

  • ThuyVy Duong

    (Johns Hopkins University School of Medicine)

  • Shengjun Hong

    (University of Lübeck)

  • Mary L. Biggs

    (University of Washington)

  • Jian’an Luan

    (University of Cambridge School of Clinical Medicine)

  • Chloe Sarnowski

    (Boston University School of Public Health)

  • Kathryn L. Lunetta

    (Boston University School of Public Health)

  • Toshiko Tanaka

    (National Institute on Aging)

  • Mary K. Wojczynski

    (Washington University School of Medicine)

  • Ryan Cvejkus

    (University of Pittsburgh, Department of Epidemiology)

  • Maria Nethander

    (Institute of Medicine, Sahlgrenska Academy, University of Gothenburg
    University of Gothenburg)

  • Sahar Ghasemi

    (University Medicine Greifswald
    University Medicine Greifswald)

  • Jingyun Yang

    (Rush University Medical Center)

  • M. Carola Zillikens

    (Erasmus Medical Center)

  • Stefan Walter

    (Rey Juan Carlos University
    CIBER of Frailty and Healthy Aging (CIBERFES))

  • Kamil Sicinski

    (University of Wisconsin-Madison)

  • Erika Kague

    (University of Bristol)

  • Cheryl L. Ackert-Bicknell

    (University of Colorado)

  • Dan E. Arking

    (Johns Hopkins University School of Medicine)

  • B. Gwen Windham

    (University of Mississippi School of Medicine)

  • Eric Boerwinkle

    (The University of Texas Health Science Center at Houston
    Human Genome Sequencing Center, Baylor College of Medicine)

  • Megan L. Grove

    (The University of Texas Health Science Center at Houston)

  • Misa Graff

    (University of North Carolina)

  • Dominik Spira

    (Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin
    Berlin Institute of Health, Department of Endocrinology and Metabolism)

  • Ilja Demuth

    (Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin
    Berlin Institute of Health, Department of Endocrinology and Metabolism
    Charité - Universitätsmedizin Berlin, BCRT - Berlin Institute of Health Center for Regenerative Therapies)

  • Nathalie Velde

    (University of Amsterdam)

  • Lisette C. P. G. M. Groot

    (Wageningen University, Division of Human Nutrition)

  • Bruce M. Psaty

    (Epidemiology, and Health services, University of Washington
    Kaiser Permanente Washington Health Research Institute)

  • Michelle C. Odden

    (Stanford University)

  • Alison E. Fohner

    (University of Washington)

  • Claudia Langenberg

    (University of Cambridge School of Clinical Medicine)

  • Nicholas J. Wareham

    (University of Cambridge School of Clinical Medicine)

  • Stefania Bandinelli

    (Geriatric Unit, Azienda Sanitaria Firenze (ASF))

  • Natasja M. Schoor

    (Amsterdam UMC- Vrije Universiteit, Amsterdam Public Health Research Institute)

  • Martijn Huisman

    (Amsterdam UMC- Vrije Universiteit, Amsterdam Public Health Research Institute)

  • Qihua Tan

    (University of Southern Denmark)

  • Joseph Zmuda

    (University of Pittsburgh, Department of Epidemiology)

  • Dan Mellström

    (Institute of Medicine, Sahlgrenska Academy, University of Gothenburg
    Geriatric Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg)

  • Magnus Karlsson

    (Lund University, Skåne University Hospital)

  • David A. Bennett

    (Rush University Medical Center)

  • Aron S. Buchman

    (Rush University Medical Center)

  • Philip L. Jager

    (Columbia University Medical Center
    Program in Medical and Population Genetics, Broad Institute)

  • Andre G. Uitterlinden

    (Erasmus Medical Center)

  • Uwe Völker

    (University Medicine Greifswald)

  • Thomas Kocher

    (University Medicine Greifswald)

  • Alexander Teumer

    (University Medicine Greifswald)

  • Leocadio Rodriguéz-Mañas

    (CIBER of Frailty and Healthy Aging (CIBERFES)
    Getafe University Hospital)

  • Francisco J. García

    (CIBER of Frailty and Healthy Aging (CIBERFES)
    Complejo Hospitalario de Toledo)

  • José A. Carnicero

    (CIBER of Frailty and Healthy Aging (CIBERFES))

  • Pamela Herd

    (Georgetown University)

  • Lars Bertram

    (University of Lübeck)

  • Claes Ohlsson

    (Institute of Medicine, Sahlgrenska Academy, University of Gothenburg
    Sahlgrenska University Hospital, Department of Drug Treatment)

  • Joanne M. Murabito

    (Boston University School of Medicine)

  • David Melzer

    (University of Exeter Medical School)

  • George A. Kuchel

    (Center on Aging, University of Connecticut Health)

  • Luigi Ferrucci

    (National Institute on Aging)

  • David Karasik

    (Marcus Institute for Aging Research, Hebrew SeniorLife
    Bar Ilan University)

  • Fernando Rivadeneira

    (Erasmus Medical Center
    Erasmus Medical Center)

  • Douglas P. Kiel

    (Beth Israel Deaconess Medical Center and Harvard Medical School, Broad Institute of MIT & Harvard)

  • Luke C. Pilling

    (University of Exeter Medical School)

Abstract

Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p = 4 × 10−17), arthritis (GDF5 p = 4 × 10−13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.

Suggested Citation

  • Garan Jones & Katerina Trajanoska & Adam J. Santanasto & Najada Stringa & Chia-Ling Kuo & Janice L. Atkins & Joshua R. Lewis & ThuyVy Duong & Shengjun Hong & Mary L. Biggs & Jian’an Luan & Chloe Sarno, 2021. "Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-20918-w
    DOI: 10.1038/s41467-021-20918-w
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    Cited by:

    1. Rosalie B. T. M. Sterenborg & Inga Steinbrenner & Yong Li & Melissa N. Bujnis & Tatsuhiko Naito & Eirini Marouli & Tessel E. Galesloot & Oladapo Babajide & Laura Andreasen & Arne Astrup & Bjørn Olav Å, 2024. "Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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