dc.contributor.author | Pilling, Luke, C | |
dc.contributor.author | Joehanes, R | |
dc.contributor.author | Kacprowski, T | |
dc.contributor.author | Peters, M | |
dc.contributor.author | Jansen, R | |
dc.contributor.author | Karasik, D | |
dc.contributor.author | Kiel, D.P. | |
dc.contributor.author | Harries, Lorna W | |
dc.contributor.author | Teumer, A | |
dc.contributor.author | Powell, J | |
dc.contributor.author | Levy, D | |
dc.contributor.author | Lin, H | |
dc.contributor.author | Lunetta, K | |
dc.contributor.author | Munson, P | |
dc.contributor.author | Bandinelli, S | |
dc.contributor.author | Henley, William E | |
dc.contributor.author | Hernandez, D | |
dc.contributor.author | Singleton, A | |
dc.contributor.author | Tanaka, T | |
dc.contributor.author | van Grootheest, G | |
dc.contributor.author | Hofman, A | |
dc.contributor.author | Uitterlinden, A.G. | |
dc.contributor.author | Biffar, R | |
dc.contributor.author | Gläser, S | |
dc.contributor.author | Homuth, G | |
dc.contributor.author | Malsch, C | |
dc.contributor.author | Völker, U | |
dc.contributor.author | Penninx, B | |
dc.contributor.author | van Meurs, J.B.J. | |
dc.contributor.author | Ferrucci, L | |
dc.contributor.author | Kocher, T | |
dc.contributor.author | Murabito, J | |
dc.contributor.author | Melzer, David | |
dc.date.accessioned | 2016-05-11T10:29:40Z | |
dc.date.issued | 2015-10-20 | |
dc.description.abstract | Background: Lower muscle strength in midlife predicts disability and mortality in later life. Bloodborne factors, including growth differentiation factor 11 (GDF11), have been linked to muscle regeneration in animal models. We aimed to identify gene transcripts associated with muscle strength in adults. Methods: Meta-analysis of whole blood gene expression (overall 17,534 unique genes measured by microarray) and hand-grip strength in four independent cohorts (n=7,781, ages: 20-104 years, weighted mean=56), adjusted for age, sex, height, weight, and leukocyte subtypes. Separate analyses were performed in subsets (older/younger than 60, male/female). Results: Expression levels of 221 genes were associated with strength after adjustment for cofactors and for multiple statistical testing, including ALAS2 (rate limiting enzyme in heme synthesis), PRF1 (perforin, a cytotoxic protein associated with inflammation), IGF1R and IGF2BP2 (both insulin like growth factor related). We identified statistical enrichment for hemoglobin biosynthesis, innate immune activation and the stress response. Ten genes were only associated in younger individuals, four in males only and one in females only. For example PIK3R2 (a negative regulator of PI3K/AKT growth pathway) was negatively associated with muscle strength in younger (<60 years) individuals but not older (>=60 years). We also show that 115 genes (52%) have not previously been linked to muscle in NCBI PubMed abstracts Conclusions: This first large-scale transcriptome study of muscle strength in human adults confirmed associations with known pathways and provides new evidence for over half of the genes identified. There may be age and sex specific gene expression signatures in blood for muscle strength. | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | FHS gene expression profiling was funded through the Division of Intramural Research
(Principal Investigator, Daniel Levy), National Heart, Lung, and Blood Institute, National
Institutes of Health, Bethesda, MD. Dr. Murabito is supported by NIH grant R01AG029451.
Dr. Kiel is supported by NIH R01 AR41398. The Framingham Heart Study is supported by
National Heart, Lung, and Blood Institute contract N01-HC-25195. | en_GB |
dc.description.sponsorship | The InCHIANTI study was supported in part by the Intramural Research Program, National
Institute on Aging, NIH, Baltimore MD USA. D.M. and L.W.H. were generously supported by
a Wellcome Trust Institutional Strategic Support Award (WT097835MF). W.E.H. was funded
by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied
Health Research and Care (CLAHRC) for the South West Peninsula. The views expressed in
this publication are those of the authors and not necessarily those of the NHS, the NIHR or
the Department of Health in England | en_GB |
dc.description.sponsorship | The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht
program of the Netherlands Organisation for Health Research and Development (Zon-Mw,
grant number 10-000-1002) and is supported by participating universities and mental health
care organizations (VU University Medical Center, GGZ inGeest, Arkin, Leiden University
Medical Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis, GGZ
Friesland, GGZ Drenthe, Scientific Institute for Quality of Healthcare (IQ healthcare),
Netherlands Institute for Health Services Research (NIVEL) and Netherlands Institute of
Mental Health and Addiction (Trimbos Institute). | en_GB |
dc.description.sponsorship | The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University,
Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw),
the Netherlands Organisation of Scientific Research NWO Investments (nr.
175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93-
28
015; RIDE2), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare
and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The
authors are grateful to the study participants, the staff from the Rotterdam Study and the
participating general practitioners and pharmacists. The generation and management of
RNA-expression array data for the Rotterdam Study was executed and funded by the Human
Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine,
Erasmus MC, the Netherlands. We thank Marjolein Peters, MSc, Ms. Mila Jhamai, Ms.
Jeannette M. Vergeer-Drop, Ms. Bernadette van Ast-Copier, Mr. Marijn Verkerk and Jeroen
van Rooij, BSc for their help in creating the RNA array expression database | en_GB |
dc.description.sponsorship | SHIP is part of the Community Medicine Research net of the University of Greifswald,
Germany, which is funded by the Federal Ministry of Education and Research (grants no.
01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social
Ministry of the Federal State of Mecklenburg-West Pomerania, and the network ‘Greifswald
Approach to Individualized Medicine (GANI_MED)’ funded by the Federal Ministry of
Education and Research (grant 03IS2061A). The University of Greifswald is a member of the
'Center of Knowledge Interchange' program of the Siemens AG and the Caché Campus
program of the InterSystems GmbH. | en_GB |
dc.identifier.citation | 1 January 2016 Vol. 48 no. 1, 1-11 DOI: 10.1152/physiolgenomics.00054.2015 | en_GB |
dc.identifier.doi | 10.1152/physiolgenomics.00054.2015 | |
dc.identifier.uri | http://hdl.handle.net/10871/21472 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/pubmed/26487704 | |
dc.language.iso | en | en_GB |
dc.publisher | American Physiological Society | en_GB |
dc.rights | Licensed under Creative Commons Attribution CC-BY 3.0: © the American Physiological Society. | en_GB |
dc.subject | Gene-expression | en_GB |
dc.subject | muscle | en_GB |
dc.subject | strength | en_GB |
dc.subject | blood | en_GB |
dc.subject | human | en_GB |
dc.subject | leukocy | en_GB |
dc.title | Gene transcripts associated with muscle strength: a CHARGE meta-analysis of 7,781 persons | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2016-05-11T10:29:40Z | |
dc.identifier.issn | 1094-8341 | |
dc.description | This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record. | en_GB |
dc.identifier.journal | Physiological Genomics | en_GB |
dc.identifier.pmid | 26487704 | |