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The complex genetics of gait speed: genome-wide meta-analysis approach.
Monday,2017-05-01 15:57 America/Los_Angeles — ecterry
| Title | The complex genetics of gait speed: genome-wide meta-analysis approach. |
| Publication Type | Journal Article |
| Year of Publication | 2017 |
| Authors | 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, AM, 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 |
| Journal | Aging (Albany NY) |
| Volume | 9 |
| Issue | 1 |
| Pagination | 209-246 |
| Date Published | 2017 Jan 10 |
| ISSN | 1945-4589 |
| Abstract | <p>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.</p> |
| DOI | 10.18632/aging.101151 |
| Alternate Journal | Aging (Albany NY) |
| PubMed ID | 28077804 |
| PubMed Central ID | PMC5310665 |
| Grant List | HHSN268201100012C / HL / NHLBI NIH HHS / United States RC4 AG039029 / AG / NIA NIH HHS / United States R01 NS041558 / NS / NINDS NIH HHS / United States HHSN268201100009I / HL / NHLBI NIH HHS / United States HHSN268201100010C / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States U01 AG009740 / AG / NIA NIH HHS / United States N01 AG062101 / AG / NIA NIH HHS / United States HHSN268201100008C / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States R01 NS078009 / NS / NINDS NIH HHS / United States HHSN268201100005G / HL / NHLBI NIH HHS / United States HHSN268201100008I / HL / NHLBI NIH HHS / United States R01 AR035583 / AR / NIAMS NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States R01 HL087660 / HL / NHLBI NIH HHS / United States HHSN268201100007C / HL / NHLBI NIH HHS / United States R01 MD009164 / MD / NIMHD NIH HHS / United States R01 AG030146 / AG / NIA NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States R01 AR035584 / AR / NIAMS NIH HHS / United States HHSN268201100011I / HL / NHLBI NIH HHS / United States HHSN268201100011C / HL / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States R01 AG017917 / AG / NIA NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States N01 AG062106 / AG / NIA NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States MR/K026992/1 / / Medical Research Council / United Kingdom R01 AG027576 / AG / NIA NIH HHS / United States U01 AR045614 / AR / NIAMS NIH HHS / United States R01 HL093029 / HL / NHLBI NIH HHS / United States R01 AR041398 / AR / NIAMS NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 HL119443 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States U01 AR045654 / AR / NIAMS NIH HHS / United States R01 AG032098 / AG / NIA NIH HHS / United States U10 HL054457 / HL / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States HHSN268200782096C / HG / NHGRI NIH HHS / United States HHSN268201100006C / HL / NHLBI NIH HHS / United States R01 AG005407 / AG / NIA NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States P30 AG010161 / AG / NIA NIH HHS / United States HHSN268201100005I / HL / NHLBI NIH HHS / United States U01 HL054457 / HL / NHLBI NIH HHS / United States N01 AG062103 / AG / NIA NIH HHS / United States R01 AG029451 / AG / NIA NIH HHS / United States U01 AR045583 / AR / NIAMS NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States U24 AG051129 / AG / NIA NIH HHS / United States R01 AR051124 / AR / NIAMS NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States HHSN268201100009C / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States HHSN268201100005C / HL / NHLBI NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States U01 AR045647 / AR / NIAMS NIH HHS / United States RC2 AR058973 / AR / NIAMS NIH HHS / United States HHSN268201100007I / HL / NHLBI NIH HHS / United States R01 AR035582 / AR / NIAMS NIH HHS / United States RC2 AG036495 / AG / NIA NIH HHS / United States U01 AG027810 / AG / NIA NIH HHS / United States R01 AG005394 / AG / NIA NIH HHS / United States BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom UL1 RR024140 / RR / NCRR NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States R56 AG023629 / AG / NIA NIH HHS / United States U01 AR045580 / AR / NIAMS NIH HHS / United States R01 AG027574 / AG / NIA NIH HHS / United States U01 AG018197 / AG / NIA NIH HHS / United States R01 AG015819 / AG / NIA NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States U01 AR045632 / AR / NIAMS NIH HHS / United States |
ePub date:
17/01