TY - JOUR
T1 - Identification of a Novel Locus for Gait Speed Decline with Aging
T2 - The Long Life Family Study
AU - Santanasto, Adam J.
AU - Wojczynski, Mary K.
AU - Cvejkus, Ryan K.
AU - Lin, Shiow
AU - Wang, Lihua
AU - Thyagarajan, Bharat
AU - Christensen, Kaare
AU - Schupf, Nicole
AU - Feitosa, Mary F.
AU - An, Ping
AU - Zmuda, Joseph M.
N1 - Funding Information:
This work was supported by the National Institute on Aging (U19-AG063893-01, U01-AG023712, U01-AG23744, U01-AG023746, U01-AG023749, and U01-AG023755). A.J.S. was supported by a career development award from the National Institute on Aging (K01 AG057726).
Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: [email protected].
PY - 2021/10/1
Y1 - 2021/10/1
N2 - Background: Gait speed is a powerful indicator of health with aging. Potential genetic contributions to gait speed and its decline with aging are not well defined. We determined the heritability of and potential genetic regions underlying change in gait speed using longitudinal data from 2379 individuals belonging to 509 families in the Long Life Family Study (mean age 64 ± 12, range 30-110 years; 45% men). Methods: Gait speed was measured over 4 m at baseline and follow-up (7 ± 1 years). Quantitative trait linkage analyses were completed using pedigree-based maximum likelihood methods with logarithm of the odds (LOD) scores greater than 3.0, indicating genome-wide significance. We also performed linkage analysis in the top 10% of families contributing to LOD scores to allow for heterogeneity among families (HLOD). Data were adjusted for age, sex, height, and field center. Results: At baseline, 26.9% of individuals had "slow"gait speed less than 1.0 m/s (mean: 1.1 ± 0.2 m/s) and gait speed declined at a rate of -0.02 ± 0.03 m/s per year (p <. 0001). Baseline and change in gait speed were significantly heritable (h2 = 0.24-0.32, p <. 05). We did not find significant evidence for linkage for baseline gait speed; however, we identified a significant locus for change in gait speed on chromosome 16p (LOD = 4.2). A subset of 21 families contributed to this linkage peak (HLOD = 6.83). Association analyses on chromosome 16 showed that the strongest variant resides within the ADCY9 gene. Conclusion: Further analysis of the chromosome 16 region, and ADCY9 gene, may yield new insight on the biology of mobility decline with aging.
AB - Background: Gait speed is a powerful indicator of health with aging. Potential genetic contributions to gait speed and its decline with aging are not well defined. We determined the heritability of and potential genetic regions underlying change in gait speed using longitudinal data from 2379 individuals belonging to 509 families in the Long Life Family Study (mean age 64 ± 12, range 30-110 years; 45% men). Methods: Gait speed was measured over 4 m at baseline and follow-up (7 ± 1 years). Quantitative trait linkage analyses were completed using pedigree-based maximum likelihood methods with logarithm of the odds (LOD) scores greater than 3.0, indicating genome-wide significance. We also performed linkage analysis in the top 10% of families contributing to LOD scores to allow for heterogeneity among families (HLOD). Data were adjusted for age, sex, height, and field center. Results: At baseline, 26.9% of individuals had "slow"gait speed less than 1.0 m/s (mean: 1.1 ± 0.2 m/s) and gait speed declined at a rate of -0.02 ± 0.03 m/s per year (p <. 0001). Baseline and change in gait speed were significantly heritable (h2 = 0.24-0.32, p <. 05). We did not find significant evidence for linkage for baseline gait speed; however, we identified a significant locus for change in gait speed on chromosome 16p (LOD = 4.2). A subset of 21 families contributed to this linkage peak (HLOD = 6.83). Association analyses on chromosome 16 showed that the strongest variant resides within the ADCY9 gene. Conclusion: Further analysis of the chromosome 16 region, and ADCY9 gene, may yield new insight on the biology of mobility decline with aging.
KW - Epidemiology
KW - Gait
KW - Genetics
KW - Physical function
UR - https://www.scopus.com/pages/publications/85116954280
U2 - 10.1093/gerona/glab177
DO - 10.1093/gerona/glab177
M3 - Article
C2 - 34156441
AN - SCOPUS:85116954280
SN - 1079-5006
VL - 76
SP - E307-E313
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 10
ER -