GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium

Amy M. Matteini, Toshiko Tanaka, David Karasik, Gil Atzmon, Wen Chi Chou, John D. Eicher, Andrew D. Johnson, Alice M. Arnold, Michele L. Callisaya, Gail Davies, Daniel S. Evans, Birte Holtfreter, Kurt Lohman, Kathryn L. Lunetta, Massimo Mangino, Albert V. Smith, Jennifer A. Smith, Alexander Teumer, Lei Yu, Dan E. Arking & 47 others Aron S. Buchman, Lori B. Chibinik, Philip L. DeJager, Denis A. Evans, Jessica D. Faul, Melissa E. Garcia, Irina Gillham-Nasenya, Vilmundur Gudnason, Albert Hofman, Yi Hsiang Hsu, Till Ittermann, Lies Lahousse, David C. Liewald, Yongmei Liu, Lorna Lopez, Fernando Rivadeneira, Jerome I. Rotter, Kristin Siggeirsdottir, John M. Starr, Russell Thomson, Gregory J. Tranah, André G. Uitterlinden, Uwe Völker, Henry Völzke, David R. Weir, Kristine Yaffe, Wei Zhao, Wei Vivian Zhuang, Joseph M. Zmuda, David A. Bennett, Steven R. Cummings, Ian J. Deary, Luigi Ferrucci, Tamara B. Harris, Sharon L R Kardia, Thomas Kocher, Stephen B. Kritchevsky, Bruce M. Psaty, Sudha Seshadri, Timothy D. Spector, Velandai K. Srikanth, B. Gwen Windham, M. Carola Zillikens, Anne B. Newman, Jeremy D. Walston, Douglas P. Kiel, Joanne M. Murabito

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    Abstract

    Decline in muscle strength with aging is an important predictor of health trajectory in the elderly. Several factors, including genetics, are proposed contributors to variability in muscle strength. To identify genetic contributors to muscle strength, a meta-analysis of genomewide association studies of handgrip was conducted. Grip strength was measured using a handheld dynamometer in 27 581 individuals of European descent over 65 years of age from 14 cohort studies. Genomewide association analysis was conducted on ~2.7 million imputed and genotyped variants (SNPs). Replication of the most significant findings was conducted using data from 6393 individuals from three cohorts. GWAS of lower body strength was also characterized in a subset of cohorts. Two genomewide significant (P-value< 5 × 10−8) and 39 suggestive (P-value< 5 × 10−5) associations were observed from meta-analysis of the discovery cohorts. After meta-analysis with replication cohorts, genomewide significant association was observed for rs752045 on chromosome 8 (β = 0.47, SE = 0.08, P-value = 5.20 × 10−10). This SNP is mapped to an intergenic region and is located within an accessible chromatin region (DNase hypersensitivity site) in skeletal muscle myotubes differentiated from the human skeletal muscle myoblasts cell line. This locus alters a binding motif of the CCAAT/enhancer-binding protein-β (CEBPB) that is implicated in muscle repair mechanisms. GWAS of lower body strength did not yield significant results. A common genetic variant in a chromosomal region that regulates myotube differentiation and muscle repair may contribute to variability in grip strength in the elderly. Further studies are needed to uncover the mechanisms that link this genetic variant with muscle strength.

    Original languageEnglish (US)
    Pages (from-to)792-800
    Number of pages9
    JournalAging Cell
    Volume15
    Issue number5
    DOIs
    StatePublished - Oct 1 2016

    Fingerprint

    Genome-Wide Association Study
    Muscle Strength
    Meta-Analysis
    Skeletal Muscle Fibers
    Hand Strength
    Single Nucleotide Polymorphism
    Skeletal Muscle
    Skeletal Myoblasts
    CCAAT-Enhancer-Binding Proteins
    Muscles
    Chromosomes, Human, Pair 8
    Intergenic DNA
    Deoxyribonucleases
    Muscle Cells
    Chromatin
    Hypersensitivity
    Cohort Studies
    Cell Line
    Health

    All Science Journal Classification (ASJC) codes

    • Aging
    • Cell Biology

    Cite this

    Matteini, A. M., Tanaka, T., Karasik, D., Atzmon, G., Chou, W. C., Eicher, J. D., ... Murabito, J. M. (2016). GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium. Aging Cell, 15(5), 792-800. https://doi.org/10.1111/acel.12468

    GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium. / Matteini, Amy M.; Tanaka, Toshiko; Karasik, David; Atzmon, Gil; Chou, Wen Chi; Eicher, John D.; Johnson, Andrew D.; Arnold, Alice M.; Callisaya, Michele L.; Davies, Gail; Evans, Daniel S.; Holtfreter, Birte; Lohman, Kurt; Lunetta, Kathryn L.; Mangino, Massimo; Smith, Albert V.; Smith, Jennifer A.; Teumer, Alexander; Yu, Lei; Arking, Dan E.; Buchman, Aron S.; Chibinik, Lori B.; DeJager, Philip L.; Evans, Denis A.; Faul, Jessica D.; Garcia, Melissa E.; Gillham-Nasenya, Irina; Gudnason, Vilmundur; Hofman, Albert; Hsu, Yi Hsiang; Ittermann, Till; Lahousse, Lies; Liewald, David C.; Liu, Yongmei; Lopez, Lorna; Rivadeneira, Fernando; Rotter, Jerome I.; Siggeirsdottir, Kristin; Starr, John M.; Thomson, Russell; Tranah, Gregory J.; Uitterlinden, André G.; Völker, Uwe; Völzke, Henry; Weir, David R.; Yaffe, Kristine; Zhao, Wei; Zhuang, Wei Vivian; Zmuda, Joseph M.; Bennett, David A.; Cummings, Steven R.; Deary, Ian J.; Ferrucci, Luigi; Harris, Tamara B.; Kardia, Sharon L R; Kocher, Thomas; Kritchevsky, Stephen B.; Psaty, Bruce M.; Seshadri, Sudha; Spector, Timothy D.; Srikanth, Velandai K.; Windham, B. Gwen; Zillikens, M. Carola; Newman, Anne B.; Walston, Jeremy D.; Kiel, Douglas P.; Murabito, Joanne M.

    In: Aging Cell, Vol. 15, No. 5, 01.10.2016, p. 792-800.

    Research output: Contribution to journalArticle

    Matteini, AM, Tanaka, T, Karasik, D, Atzmon, G, Chou, WC, Eicher, JD, Johnson, AD, Arnold, AM, Callisaya, ML, Davies, G, Evans, DS, Holtfreter, B, Lohman, K, Lunetta, KL, Mangino, M, Smith, AV, Smith, JA, Teumer, A, Yu, L, Arking, DE, Buchman, AS, Chibinik, LB, DeJager, PL, Evans, DA, Faul, JD, Garcia, ME, Gillham-Nasenya, I, Gudnason, V, Hofman, A, Hsu, YH, Ittermann, T, Lahousse, L, Liewald, DC, Liu, Y, Lopez, L, Rivadeneira, F, Rotter, JI, Siggeirsdottir, K, Starr, JM, Thomson, R, Tranah, GJ, Uitterlinden, AG, Völker, U, Völzke, H, Weir, DR, Yaffe, K, Zhao, W, Zhuang, WV, Zmuda, JM, Bennett, DA, Cummings, SR, Deary, IJ, Ferrucci, L, Harris, TB, Kardia, SLR, Kocher, T, Kritchevsky, SB, Psaty, BM, Seshadri, S, Spector, TD, Srikanth, VK, Windham, BG, Zillikens, MC, Newman, AB, Walston, JD, Kiel, DP & Murabito, JM 2016, 'GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium', Aging Cell, vol. 15, no. 5, pp. 792-800. https://doi.org/10.1111/acel.12468
    Matteini AM, Tanaka T, Karasik D, Atzmon G, Chou WC, Eicher JD et al. GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium. Aging Cell. 2016 Oct 1;15(5):792-800. https://doi.org/10.1111/acel.12468
    Matteini, Amy M. ; Tanaka, Toshiko ; Karasik, David ; Atzmon, Gil ; Chou, Wen Chi ; Eicher, John D. ; Johnson, Andrew D. ; Arnold, Alice M. ; Callisaya, Michele L. ; Davies, Gail ; Evans, Daniel S. ; Holtfreter, Birte ; Lohman, Kurt ; Lunetta, Kathryn L. ; Mangino, Massimo ; Smith, Albert V. ; Smith, Jennifer A. ; Teumer, Alexander ; Yu, Lei ; Arking, Dan E. ; Buchman, Aron S. ; Chibinik, Lori B. ; DeJager, Philip L. ; Evans, Denis A. ; Faul, Jessica D. ; Garcia, Melissa E. ; Gillham-Nasenya, Irina ; Gudnason, Vilmundur ; Hofman, Albert ; Hsu, Yi Hsiang ; Ittermann, Till ; Lahousse, Lies ; Liewald, David C. ; Liu, Yongmei ; Lopez, Lorna ; Rivadeneira, Fernando ; Rotter, Jerome I. ; Siggeirsdottir, Kristin ; Starr, John M. ; Thomson, Russell ; Tranah, Gregory J. ; Uitterlinden, André G. ; Völker, Uwe ; Völzke, Henry ; Weir, David R. ; Yaffe, Kristine ; Zhao, Wei ; Zhuang, Wei Vivian ; Zmuda, Joseph M. ; Bennett, David A. ; Cummings, Steven R. ; Deary, Ian J. ; Ferrucci, Luigi ; Harris, Tamara B. ; Kardia, Sharon L R ; Kocher, Thomas ; Kritchevsky, Stephen B. ; Psaty, Bruce M. ; Seshadri, Sudha ; Spector, Timothy D. ; Srikanth, Velandai K. ; Windham, B. Gwen ; Zillikens, M. Carola ; Newman, Anne B. ; Walston, Jeremy D. ; Kiel, Douglas P. ; Murabito, Joanne M. / GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium. In: Aging Cell. 2016 ; Vol. 15, No. 5. pp. 792-800.
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    title = "GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium",
    abstract = "Decline in muscle strength with aging is an important predictor of health trajectory in the elderly. Several factors, including genetics, are proposed contributors to variability in muscle strength. To identify genetic contributors to muscle strength, a meta-analysis of genomewide association studies of handgrip was conducted. Grip strength was measured using a handheld dynamometer in 27 581 individuals of European descent over 65 years of age from 14 cohort studies. Genomewide association analysis was conducted on ~2.7 million imputed and genotyped variants (SNPs). Replication of the most significant findings was conducted using data from 6393 individuals from three cohorts. GWAS of lower body strength was also characterized in a subset of cohorts. Two genomewide significant (P-value< 5 × 10−8) and 39 suggestive (P-value< 5 × 10−5) associations were observed from meta-analysis of the discovery cohorts. After meta-analysis with replication cohorts, genomewide significant association was observed for rs752045 on chromosome 8 (β = 0.47, SE = 0.08, P-value = 5.20 × 10−10). This SNP is mapped to an intergenic region and is located within an accessible chromatin region (DNase hypersensitivity site) in skeletal muscle myotubes differentiated from the human skeletal muscle myoblasts cell line. This locus alters a binding motif of the CCAAT/enhancer-binding protein-β (CEBPB) that is implicated in muscle repair mechanisms. GWAS of lower body strength did not yield significant results. A common genetic variant in a chromosomal region that regulates myotube differentiation and muscle repair may contribute to variability in grip strength in the elderly. Further studies are needed to uncover the mechanisms that link this genetic variant with muscle strength.",
    author = "Matteini, {Amy M.} and Toshiko Tanaka and David Karasik and Gil Atzmon and Chou, {Wen Chi} and Eicher, {John D.} and Johnson, {Andrew D.} and Arnold, {Alice M.} and Callisaya, {Michele L.} and Gail Davies and Evans, {Daniel S.} and Birte Holtfreter and Kurt Lohman and Lunetta, {Kathryn L.} and Massimo Mangino and Smith, {Albert V.} and Smith, {Jennifer A.} and Alexander Teumer and Lei Yu and Arking, {Dan E.} and Buchman, {Aron S.} and Chibinik, {Lori B.} and DeJager, {Philip L.} and Evans, {Denis A.} and Faul, {Jessica D.} and Garcia, {Melissa E.} and Irina Gillham-Nasenya and Vilmundur Gudnason and Albert Hofman and Hsu, {Yi Hsiang} and Till Ittermann and Lies Lahousse and Liewald, {David C.} and Yongmei Liu and Lorna Lopez and Fernando Rivadeneira and Rotter, {Jerome I.} and Kristin Siggeirsdottir and Starr, {John M.} and Russell Thomson and Tranah, {Gregory J.} and Uitterlinden, {Andr{\'e} G.} and Uwe V{\"o}lker and Henry V{\"o}lzke and Weir, {David R.} and Kristine Yaffe and Wei Zhao and Zhuang, {Wei Vivian} and Zmuda, {Joseph M.} and Bennett, {David A.} and Cummings, {Steven R.} and Deary, {Ian J.} and Luigi Ferrucci and Harris, {Tamara B.} and Kardia, {Sharon L R} and Thomas Kocher and Kritchevsky, {Stephen B.} and Psaty, {Bruce M.} and Sudha Seshadri and Spector, {Timothy D.} and Srikanth, {Velandai K.} and Windham, {B. Gwen} and Zillikens, {M. Carola} and Newman, {Anne B.} and Walston, {Jeremy D.} and Kiel, {Douglas P.} and Murabito, {Joanne M.}",
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    AU - Matteini, Amy M.

    AU - Tanaka, Toshiko

    AU - Karasik, David

    AU - Atzmon, Gil

    AU - Chou, Wen Chi

    AU - Eicher, John D.

    AU - Johnson, Andrew D.

    AU - Arnold, Alice M.

    AU - Callisaya, Michele L.

    AU - Davies, Gail

    AU - Evans, Daniel S.

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    AU - Lohman, Kurt

    AU - Lunetta, Kathryn L.

    AU - Mangino, Massimo

    AU - Smith, Albert V.

    AU - Smith, Jennifer A.

    AU - Teumer, Alexander

    AU - Yu, Lei

    AU - Arking, Dan E.

    AU - Buchman, Aron S.

    AU - Chibinik, Lori B.

    AU - DeJager, Philip L.

    AU - Evans, Denis A.

    AU - Faul, Jessica D.

    AU - Garcia, Melissa E.

    AU - Gillham-Nasenya, Irina

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    AU - Hsu, Yi Hsiang

    AU - Ittermann, Till

    AU - Lahousse, Lies

    AU - Liewald, David C.

    AU - Liu, Yongmei

    AU - Lopez, Lorna

    AU - Rivadeneira, Fernando

    AU - Rotter, Jerome I.

    AU - Siggeirsdottir, Kristin

    AU - Starr, John M.

    AU - Thomson, Russell

    AU - Tranah, Gregory J.

    AU - Uitterlinden, André G.

    AU - Völker, Uwe

    AU - Völzke, Henry

    AU - Weir, David R.

    AU - Yaffe, Kristine

    AU - Zhao, Wei

    AU - Zhuang, Wei Vivian

    AU - Zmuda, Joseph M.

    AU - Bennett, David A.

    AU - Cummings, Steven R.

    AU - Deary, Ian J.

    AU - Ferrucci, Luigi

    AU - Harris, Tamara B.

    AU - Kardia, Sharon L R

    AU - Kocher, Thomas

    AU - Kritchevsky, Stephen B.

    AU - Psaty, Bruce M.

    AU - Seshadri, Sudha

    AU - Spector, Timothy D.

    AU - Srikanth, Velandai K.

    AU - Windham, B. Gwen

    AU - Zillikens, M. Carola

    AU - Newman, Anne B.

    AU - Walston, Jeremy D.

    AU - Kiel, Douglas P.

    AU - Murabito, Joanne M.

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