Gene transcripts associated with muscle strength: A CHARGE meta-analysis of 7,781 persons

Pilling, L.C., Joehanes, R., Kacprowski,T., Peters, M., Jansen, R., Karasik, D., Kiel, D.P., Harries, L.W., Teumer, A., Powell, J., Levy, D., Lin, H., Lunetta, K., Munson, P., Bandinelli, S., Henley, W., Hernandez, D., Singleton, A., Tanaka, T., van Grootheest, G., Hofman, A., Uitterlinden, A.G., Biffar, R., Glaser, S., Homuth, G., Malsch, C., Volker, U., Penninx, B., van Meurs, J.B.J., Ferrucci, L., Kocher, T., Murabito, J. and Melzer, D. (2016) Gene transcripts associated with muscle strength: A CHARGE meta-analysis of 7,781 persons. Physiological Genomics, 48 1: 1-11. doi:10.1152/physiolgenomics.00054.2015


Author Pilling, L.C.
Joehanes, R.
Kacprowski,T.
Peters, M.
Jansen, R.
Karasik, D.
Kiel, D.P.
Harries, L.W.
Teumer, A.
Powell, J.
Levy, D.
Lin, H.
Lunetta, K.
Munson, P.
Bandinelli, S.
Henley, W.
Hernandez, D.
Singleton, A.
Tanaka, T.
van Grootheest, G.
Hofman, A.
Uitterlinden, A.G.
Biffar, R.
Glaser, S.
Homuth, G.
Malsch, C.
Volker, U.
Penninx, B.
van Meurs, J.B.J.
Ferrucci, L.
Kocher, T.
Murabito, J.
Melzer, D.
Title Gene transcripts associated with muscle strength: A CHARGE meta-analysis of 7,781 persons
Journal name Physiological Genomics   Check publisher's open access policy
ISSN 1531-2267
1094-8341
Publication date 2016-01-01
Year available 2015
Sub-type Article (original research)
DOI 10.1152/physiolgenomics.00054.2015
Open Access Status Not Open Access
Volume 48
Issue 1
Start page 1
End page 11
Total pages 11
Place of publication Bethesda, United States
Publisher American Physiological Society
Language eng
Subject 1314 Physiology
1311 Genetics
Abstract Lower muscle strength in midlife predicts disability and mortality in later life. Blood-borne 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. 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 yr, weighted mean = 56), adjusted for age, sex, height, weight, and leukocyte subtypes. Separate analyses were performed in subsets (older/younger than 60, men/women). 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 associated only in younger individuals, four in men only and one in women only. For example, PIK3R2 (a negative regulator of PI3K/AKT growth pathway) was negatively associated with muscle strength in younger (<60 yr) individuals but not older (≥60 yr). We also show that 115 genes (52%) have not previously been linked to muscle in NCBI PubMed abstracts. 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.
Formatted abstract
Lower muscle strength in midlife predicts disability and mortality in later life. Blood-borne 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. 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 yr, weighted mean = 56), adjusted for age, sex, height, weight, and leukocyte subtypes. Separate analyses were performed in subsets (older/younger than 60, men/women). 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 associated only in younger individuals, four in men only and one in women only. For example, PIK3R2 (a negative regulator of PI3K/AKT growth pathway) was negatively associated with muscle strength in younger (<60 yr) individuals but not older (≥60 yr). We also show that 115 genes (52%) have not previously been linked to muscle in NCBI PubMed abstracts. 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.
Keyword Blood
Gene-expression
Human
Leukocyte
Muscle
Strength
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Published online 20 October 2015

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
Centre for Neurogenetics and Statistical Genomics Publications
 
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