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The complex genetics of gait speed: genome-wide meta-analysis approach.

Publication ,  Journal Article
Ben-Avraham, D; Karasik, D; Verghese, J; Lunetta, KL; Smith, JA; Eicher, JD; Vered, R; Deelen, J; Arnold, AM; Buchman, AS; Tanaka, T; Faul, JD ...
Published in: Aging (Albany NY)
January 10, 2017

Emerging evidence suggests that the basis for variation in late-life mobility is attributable, in part, to genetic factors, which may become increasingly important with age. Our objective was to systematically assess the contribution of genetic variation to gait speed in older individuals. We conducted a meta-analysis of gait speed GWASs in 31,478 older adults from 17 cohorts of the CHARGE consortium, and validated our results in 2,588 older adults from 4 independent studies. We followed our initial discoveries with network and eQTL analysis of candidate signals in tissues. The meta-analysis resulted in a list of 536 suggestive genome wide significant SNPs in or near 69 genes. Further interrogation with Pathway Analysis placed gait speed as a polygenic complex trait in five major networks. Subsequent eQTL analysis revealed several SNPs significantly associated with the expression of PRSS16, WDSUB1 and PTPRT, which in addition to the meta-analysis and pathway suggested that genetic effects on gait speed may occur through synaptic function and neuronal development pathways. No genome-wide significant signals for gait speed were identified from this moderately large sample of older adults, suggesting that more refined physical function phenotypes will be needed to identify the genetic basis of gait speed in aging.

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Published In

Aging (Albany NY)

DOI

EISSN

1945-4589

Publication Date

January 10, 2017

Volume

9

Issue

1

Start / End Page

209 / 246

Location

United States

Related Subject Headings

  • Walking Speed
  • Serine Endopeptidases
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
 

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Ben-Avraham, D., Karasik, D., Verghese, J., Lunetta, K. L., Smith, J. A., Eicher, J. D., … Atzmon, G. (2017). The complex genetics of gait speed: genome-wide meta-analysis approach. Aging (Albany NY), 9(1), 209–246. https://doi.org/10.18632/aging.101151
Ben-Avraham, Dan, David Karasik, Joe Verghese, Kathryn L. Lunetta, Jennifer A. Smith, John D. Eicher, Rotem Vered, et al. “The complex genetics of gait speed: genome-wide meta-analysis approach.Aging (Albany NY) 9, no. 1 (January 10, 2017): 209–46. https://doi.org/10.18632/aging.101151.
Ben-Avraham D, Karasik D, Verghese J, Lunetta KL, Smith JA, Eicher JD, et al. The complex genetics of gait speed: genome-wide meta-analysis approach. Aging (Albany NY). 2017 Jan 10;9(1):209–46.
Ben-Avraham, Dan, et al. “The complex genetics of gait speed: genome-wide meta-analysis approach.Aging (Albany NY), vol. 9, no. 1, Jan. 2017, pp. 209–46. Pubmed, doi:10.18632/aging.101151.
Ben-Avraham D, Karasik D, Verghese J, Lunetta KL, Smith JA, Eicher JD, Vered R, Deelen J, Arnold AM, Buchman AS, Tanaka T, Faul JD, Nethander M, Fornage M, Adams HH, Matteini AM, Callisaya ML, Smith AV, Yu L, De Jager PL, Evans DA, Gudnason V, Hofman A, Pattie A, Corley J, Launer LJ, Knopman DS, Parimi N, Turner ST, Bandinelli S, Beekman M, Gutman D, Sharvit L, Mooijaart SP, Liewald DC, Houwing-Duistermaat JJ, Ohlsson C, Moed M, Verlinden VJ, Mellström D, van der Geest JN, Karlsson M, Hernandez D, McWhirter R, Liu Y, Thomson R, Tranah GJ, Uitterlinden AG, Weir DR, Zhao W, Starr JM, Johnson AD, Ikram MA, Bennett DA, Cummings SR, Deary IJ, Harris TB, Kardia SLR, Mosley TH, Srikanth VK, Windham BG, Newman AB, Walston JD, Davies G, Evans DS, Slagboom EP, Ferrucci L, Kiel DP, Murabito JM, Atzmon G. The complex genetics of gait speed: genome-wide meta-analysis approach. Aging (Albany NY). 2017 Jan 10;9(1):209–246.

Published In

Aging (Albany NY)

DOI

EISSN

1945-4589

Publication Date

January 10, 2017

Volume

9

Issue

1

Start / End Page

209 / 246

Location

United States

Related Subject Headings

  • Walking Speed
  • Serine Endopeptidases
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study