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Nat Commun. 2017 Jul 12;8:16015. doi: 10.1038/ncomms16015.

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

Author information

1
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK.
2
Department of Internal Medicine, Erasmus Medical Center, 3015 CE Rotterdam, The Netherlands.
3
Department of Epidemiology, Erasmus Medical Center, 3015 CE Rotterdam, The Netherlands.
4
Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH8 9AB, UK.
5
Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec, Canada QC H3T 1E2.
6
Department of Human Genetics, McGill University, Montreal, Quebec, Canada H3G 0B1.
7
Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
8
Queensland Brain Institute, University of Queensland, St Lucia, Queensland 4072, Australia.
9
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
10
Lund University Diabetes Center, Department of Clinical Sciences, Diabetes and Endocrinology, Skånes University Hospital, 222 41 Lund, Sweden.
11
Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, New South Wales 2031, Australia.
12
Department of Twin Research &Genetic Epidemiology, Kings College London, London SE1 7EH, UK.
13
NIHR Biomedical Research Centre at Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK.
14
Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
15
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Maryland 02114, USA.
16
Harvard Medical School, Boston, Maryland 02115, USA.
17
Centre for Sport and Exercise Science and Medicine (SESAME), University of Brighton, Eastbourne BN20 7SN, UK.
18
Hunter Medical Research Institute, Newcastle, New South Wales 2305, Australia.
19
Department of Pediatrics, University of California San Diego, La Jolla, California 92093, USA.
20
Japan Society for the Promotion of Science, Tokyo 102-0083, Japan.
21
Department of Sports and Life Science, National Institute of Fitness and Sports, Kanoya, Kagoshima 891-2393, Japan.
22
Department of Biomedical Data Sciences, Stanford University, Stanford, California 94305, USA.
23
BROAD Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
24
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.
25
Research Centre for Prevention and Health, Capital Region of Denmark, Glostrup University Hospital, DK-2600 Glostrup, Denmark.
26
Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales 2308, Australia.
27
John Hunter Hospital, New Lambton, New South Wales 2305, Australia.
28
Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland 4072, Australia.
29
Division of Endocrinology Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
30
Faculty of Physical Education, Gdańsk University of Physical Education and Sport, 80-336 Gdańsk, Poland.
31
Department of Movement and Sports Sciences, Ghent University, 9000 Ghent, Belgium.
32
Institute of Sport, Exercise &Active Living (ISEAL), Victoria University, Melbourne, Victoria 8001, Australia.
33
Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria 3052, Australia.
34
Department of Clinical Experimental Research, Rigshospitalet, 2600 Glostrup, Denmark.
35
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
36
Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Madrid, Spain.
37
Research Institute 'i+12', Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.
38
Department of Life and Environmental Sciences, University of Cagliari, 09124 Cagliari, Italy.
39
Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, Maryland 21201, USA.
40
National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo 162-8636, Japan.
41
British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
42
Target Sciences, GlaxoSmithKline, King of Prussia, Pennsylvania 19406, USA.
43
Musculoskeletal Physiology Research Group, Sport, Health and Performance Enhancement (SHAPE) Research Centre, Nottingham Trent University, Nottingham NG1 4FQ, UK.
44
Department of Clinical and Experimental Medicine, Medical Genetics, University of Foggia, 71122 Foggia FG, Italy.
45
Department of Health Sciences, University of Leicester, Leicester LE1 7RH, UK.
46
National Institute for Health Research, Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK.
47
The Big Data Institute, University of Oxford, Oxford OX3 7BN, UK.
48
Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
49
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LE, UK.
50
NIHR Oxford Biomedical Research Centre, Oxford OX3 7LE, UK.
51
Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 0SR, UK.
52
Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts 02131, USA.
53
Department of Medicine, Beth Israel Deaconess Medical Centre, Boston, Massachusetts 02215, USA.
54
Graduate School of Health and Sports Science, Juntendo University, Chiba 270-1695, Japan.
55
Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Skånes University Hospital, 222 41 Lund, Sweden.
56
Public Health and Clinical Medicine, Section for Medicine, Umeå University, 901 87 Umeå, Sweden.
57
Biobank Research, Umeå University, 901 87 Umeå, Sweden.
58
Faculty of Health Sciences, University of Southern Denmark, 5230 Odense M, Denmark.
59
Boston University School of Medicine, Department of Medicine, Section of General Internal Medicine, Boston, Massachusetts 02118, USA.
60
National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts 01702, USA.
61
Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4.

Abstract

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.

PMID:
29313844
PMCID:
PMC5510175
DOI:
10.1038/ncomms16015
[Indexed for MEDLINE]
Free PMC Article

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