Article open access publication

Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness

Nature Communications, Springer Nature, ISSN 2041-1723

Volume 8, 1, 2017

DOI:10.1038/ncomms16015, Dimensions: pub.1090616280, PMC: PMC5510175, PMID: 29313844,

Authors

Morris, John A (4) (5)
Mangino, Massimo (11) (12)
Liu, Jun (2)
Demirkan, Ayse (2) (13)
Lek, Monkol (14) (15)
Xu, Liwen (14) (15)
Wang, Guan (16)
Rivas, Manuel A (21) (22)
Loh, Po-Ru (14) (22)
Attia, John R. (17) (24) (25)
Eynon, Nir (29) (30)
Linneberg, Allan (8) (23) (31)
Lucia, Alejandro (32) (33)
Shrine, Nick (41) (42)
Tobin, Martin D (41) (42)
Wain, Louise V (41) (42)
Lindgren, Cecilia M. (22) (43) (44)
McCarthy, Mark I. (43) (44) (45)
Kiel, Douglas P (14) (46)
Franks, Paul W. (9) (48)
Hansen, Torben (8) (49)
Murabito, Joanne M (50) (51)
Richards, J. Brent (4) (5) (12)

* Corresponding author

Affiliations

Organisations

  1. (1) University of Cambridge, grid.5335.0
  2. (2) Erasmus University Medical Center, grid.5645.2
  3. (3) University of Edinburgh, grid.4305.2
  4. (4) Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, QC H3T 1E2, Montreal, Quebec, Canada
  5. (5) McGill University, grid.14709.3b
  6. (6) Johns Hopkins University, grid.21107.35
  7. (7) University of Queensland, grid.1003.2
  8. (8) University of Copenhagen, grid.5254.6, KU
  9. (9) Lund University, grid.4514.4
  10. (10) UNSW Sydney, grid.1005.4
  11. (11) National Institute for Health Research, grid.451056.3
  12. (12) King's College London, grid.13097.3c
  13. (13) Leiden University Medical Center, grid.10419.3d
  14. (14) Harvard University, grid.38142.3c
  15. (15) Massachusetts General Hospital, grid.32224.35
  16. (16) University of Brighton, grid.12477.37
  17. (17) Hunter Medical Research Institute, grid.413648.c
  18. (18) University of California, San Diego, grid.266100.3
  19. (19) Japan Society for the Promotion of Science, grid.54432.34
  20. (20) National Institute of Fitness and Sports in Kanoya, grid.419589.8
  21. (21) Stanford University, grid.168010.e
  22. (22) Broad Institute, grid.66859.34
  23. (23) Rigshospitalet, grid.475435.4, Capital Region
  24. (24) John Hunter Hospital, grid.414724.0
  25. (25) University of Newcastle Australia, grid.266842.c
  26. (26) University of Maryland, Baltimore, grid.411024.2
  27. (27) Gdansk University of Physical Education and Sport, grid.445131.6
  28. (28) Ghent University, grid.5342.0
  29. (29) Victoria University, grid.1019.9
  30. (30) Murdoch Children’s Research Institute, Royal Children’s Hospital, 3052, Melbourne, Victoria, Australia
  31. (31) Department of Clinical Experimental Research, 2600, Rigshospitalet, Glostrup, Denmark
  32. (32) European University of Madrid, grid.119375.8
  33. (33) Hospital Universitario 12 De Octubre, grid.144756.5
  34. (34) University of Cagliari, grid.7763.5
  35. (35) Baltimore VA Medical Center, grid.280711.d
  36. (36) National Institute of Biomedical Innovation, Health and Nutrition, grid.482562.f
  37. (37) University of Glasgow, grid.8756.c
  38. (38) GlaxoSmithKline (United States), grid.418019.5
  39. (39) Nottingham Trent University, grid.12361.37
  40. (40) University of Foggia, grid.10796.39
  41. (41) Glenfield Hospital, grid.412925.9
  42. (42) University of Leicester, grid.9918.9
  43. (43) University of Oxford, grid.4991.5
  44. (44) Wellcome Centre for Human Genetics, grid.270683.8
  45. (45) NIHR Oxford Musculoskeletal Biomedical Research Centre, grid.454382.c
  46. (46) Beth Israel Deaconess Medical Center, grid.239395.7
  47. (47) Juntendo University, grid.258269.2
  48. (48) Umeå University, grid.12650.30
  49. (49) University of Southern Denmark, grid.10825.3e, SDU
  50. (50) Boston University School of Medicine, grid.475010.7
  51. (51) National Heart Lung and Blood Institute, grid.279885.9

Description

Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10-8) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.

Funders

Funders and Grants

Research Categories

Main Subject Area

Fields of Research

Sustainable Development Goals

Links & Metrics

NORA University Profiles

University of Copenhagen

University of Southern Denmark

Danish Open Access Indicator

2017: Realized

Research area: Medicine

Danish Bibliometrics Indicator

2017: Level 2

Research area: Medicine

Dimensions Citation Indicators

Times Cited: 51

Field Citation Ratio (FCR): 10.72

Relative Citation ratio (RCR): 3.49

Open Access Info

Pure Gold