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

TitleGWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium.
Publication TypeJournal Article
Year of Publication2016
AuthorsMatteini, AM, Tanaka, T, Karasik, D, Atzmon, G, Chou, W-C, Eicher, JD, Johnson, AD, Arnold, AM, Callisaya, ML, Davies, G, Evans, DS, Holtfreter, B, Lohman, K, Lunetta, KL, Mangino, M, Smith, AVernon, Smith, JA, Teumer, A, Yu, L, Arking, DE, Buchman, AS, Chibinik, LB, De Jager, PL, Faul, JD, Garcia, ME, Gillham-Nasenya, I, Gudnason, V, Hofman, A, Hsu, Y-H, 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, M Zillikens, C, Newman, AB, Walston, JD, Kiel, DP, Murabito, JM
JournalAging Cell
Volume15
Issue5
Pagination792-800
Date Published2016 10
ISSN Number1474-9726
KeywordsAdult, Aged, Chromatin Immunoprecipitation, Cohort Studies, Epigenesis, Genetic, Genome-Wide Association Study, Hand Strength, Humans, Molecular Sequence Annotation, Muscle Strength, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Reproducibility of Results
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.

DOI10.1111/acel.12468
User Guide Notes

http://www.ncbi.nlm.nih.gov/pubmed/27325353?dopt=Abstract

Alternate JournalAging Cell
Citation Key8614
PubMed ID27325353
PubMed Central IDPMC5013019
Grant ListUL1 RR024140 / RR / NCRR NIH HHS / United States
/ BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
P30 AG010161 / AG / NIA NIH HHS / United States
R01 AR035582 / AR / NIAMS NIH HHS / United States
R01 AG005407 / AG / NIA NIH HHS / United States
R01 AR051124 / AR / NIAMS NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
R01 AG040039 / AG / NIA NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
U01 AR045583 / AR / NIAMS NIH HHS / United States
P30 AG024827 / AG / NIA NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
R01 AR035583 / AR / NIAMS NIH HHS / United States
RC2 AR058973 / AR / NIAMS NIH HHS / United States
RF1 AG015819 / AG / NIA NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
N01 AG062103 / AG / NIA NIH HHS / United States
R01 AG030146 / AG / NIA NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
U01 AG009740 / AG / NIA NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
U19 AG023122 / AG / NIA NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
N01 AG062106 / AG / NIA NIH HHS / United States
U01 AG018197 / AG / NIA NIH HHS / United States
P30 AG021334 / AG / NIA NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
R01 AG027576 / AG / NIA NIH HHS / United States
N01 HC085086 / HC / NHLBI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
R56 AG029451 / AG / NIA NIH HHS / United States
MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom
R01 AG015819 / AG / NIA NIH HHS / United States
FP7/2007–2013 / WT_ / Wellcome Trust / United Kingdom
R01 AR041398 / AR / NIAMS NIH HHS / United States
U01 AR045647 / AR / NIAMS NIH HHS / United States
U01 AR045632 / AR / NIAMS NIH HHS / United States
N02 HL64278 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
HHSN271201200022C / AG / NIA NIH HHS / United States
N01AG12100 / AG / NIA NIH HHS / United States
R01 AR035584 / AR / NIAMS NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 AG032098 / AG / NIA NIH HHS / United States
RC1 AG035835 / AG / NIA NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
U01 AR045654 / AR / NIAMS NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
R01 AG029451 / AG / NIA NIH HHS / United States
N01 AG062101 / AG / NIA NIH HHS / United States
RC2 AG036495 / AG / NIA NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
U01 AG027810 / AG / NIA NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268200782096C / HG / NHGRI NIH HHS / United States
U24 AG051129 / AG / NIA NIH HHS / United States
U01 AR045580 / AR / NIAMS NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
R01 AG005394 / AG / NIA NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
R01 AG024480 / AG / NIA NIH HHS / United States
R01 AG027574 / AG / NIA NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
U01 AR066160 / AR / NIAMS NIH HHS / United States
U01 AR045614 / AR / NIAMS NIH HHS / United States