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; 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

doi:10.1111/acel.12468

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. ArkingAron 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

Bar-Ilan University - Azrieli Faculty of Medicine

Research output: Contribution to journal › Article › peer-review

47 Scopus citations

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 language	English
Pages (from-to)	792-800
Number of pages	9
Journal	Aging Cell
Volume	15
Issue number	5
DOIs	https://doi.org/10.1111/acel.12468
State	Published - 1 Oct 2016

Bibliographical note

Publisher Copyright:
© 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Funding

The Longevity Consortium, funded by the National Institute of Aging, grant number U19 AG023122, provided administrative resources for this work. Dr. Bruce Psaty serves on the DSMB for a clinical trial of a device funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Dr. Kiel has received grant funding from Eli Lilly and has served on a scientific advisory board from Novartis.

Funders	Funder number
National Institute on Aging	U19 AG023122, N01AG062106
Eli Lilly and Company
Johnson and Johnson
Novartis

Keywords

SNP
aging
genomewide association
meta-analysis
muscle strength
older adults

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1111/acel.12468

Cite this

Matteini, A. M., Tanaka, T., Karasik, D., Atzmon, G., Chou, W. C., Eicher, J. D., Johnson, A. D., Arnold, A. M., Callisaya, M. L., Davies, G., Evans, D. S., Holtfreter, B., Lohman, K., Lunetta, K. L., Mangino, M., Smith, A. V., Smith, J. A., Teumer, A., Yu, L., ... 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

@article{d4821338a06b4031b1b2c45fd96bc62c,

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.",

keywords = "SNP, aging, genomewide association, meta-analysis, muscle strength, older adults",

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.}",

note = "Publisher Copyright: {\textcopyright} 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.",

year = "2016",

month = oct,

day = "1",

doi = "10.1111/acel.12468",

language = "אנגלית",

volume = "15",

pages = "792--800",

journal = "Aging Cell",

issn = "1474-9718",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "5",

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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

TY - JOUR

T1 - GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium

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.

AU - Holtfreter, Birte

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

AU - Gudnason, Vilmundur

AU - Hofman, Albert

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.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - 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.

AB - 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.

KW - SNP

KW - aging

KW - genomewide association

KW - meta-analysis

KW - muscle strength

KW - older adults

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U2 - 10.1111/acel.12468

DO - 10.1111/acel.12468

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 27325353

AN - SCOPUS:84986184309

SN - 1474-9718

VL - 15

SP - 792

EP - 800

JO - Aging Cell

JF - Aging Cell

IS - 5

ER -

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

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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