TY - JOUR
T1 - Gene transcripts associated with muscle strength
T2 - A CHARGE meta-analysis of 7,781 persons
AU - Pilling, L. C.
AU - Joehanes, R.
AU - Kacprowski, T.
AU - Peters, M.
AU - Jansen, R.
AU - Karasik, D.
AU - Kiel, D. P.
AU - Harries, L. W.
AU - Teumer, A.
AU - Powell, J.
AU - Levy, D.
AU - Lin, H.
AU - Lunetta, K.
AU - Munson, P.
AU - Bandinelli, S.
AU - Henley, W.
AU - Hernandez, D.
AU - Singleton, A.
AU - Tanaka, T.
AU - van Grootheest, G.
AU - Hofman, A.
AU - Uitterlinden, A. G.
AU - Biffar, R.
AU - Gläser, S.
AU - Homuth, G.
AU - Malsch, C.
AU - Völker, U.
AU - Penninx, B.
AU - van Meurs, J. B J
AU - Ferrucci, L.
AU - Kocher, T.
AU - Murabito, J.
AU - Melzer, D.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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 (
AB - 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 (
KW - Blood
KW - Gene-expression
KW - Human
KW - Leukocyte
KW - Muscle
KW - Strength
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U2 - 10.1152/physiolgenomics.00054.2015
DO - 10.1152/physiolgenomics.00054.2015
M3 - Article
C2 - 26487704
AN - SCOPUS:84953286347
SN - 1094-8341
VL - 48
SP - 1
EP - 11
JO - Physiological Genomics
JF - Physiological Genomics
IS - 1
ER -