TY - JOUR T1 - The complex genetics of gait speed: genome-wide meta-analysis approach. JF - Aging (Albany NY) Y1 - 2017 A1 - Ben-Avraham, Dan A1 - Karasik, David A1 - Joe Verghese A1 - Kathryn L Lunetta A1 - John D Eicher A1 - Vered, Rotem A1 - Deelen, Joris A1 - Alice M. Arnold A1 - Aron S Buchman A1 - Toshiko Tanaka A1 - Jessica Faul A1 - Nethander, Maria A1 - Myriam Fornage A1 - Hieab H Adams A1 - Amy M Matteini A1 - Michele L Callisaya A1 - Albert Vernon Smith A1 - Lei Yu A1 - Philip L de Jager A1 - Denis A Evans A1 - Gudnason, Vilmundur A1 - Hofman, Albert A1 - Pattie, Alison A1 - Corley, Janie A1 - Lenore J Launer A1 - David S Knopman A1 - Parimi, Neeta A1 - Stephen T Turner A1 - Bandinelli, Stefania A1 - Beekman, Marian A1 - Gutman, Danielle A1 - Sharvit, Lital A1 - Simon P Mooijaart A1 - David C Liewald A1 - Jeanine J Houwing-Duistermaat A1 - Ohlsson, Claes A1 - Moed, Matthijs A1 - Vincent J Verlinden A1 - Mellström, Dan A1 - Jos N van der Geest A1 - Karlsson, Magnus A1 - Dena G Hernandez A1 - McWhirter, Rebekah A1 - Yongmei Liu A1 - Thomson, Russell A1 - Tranah, Gregory J A1 - André G Uitterlinden A1 - David R Weir A1 - Wei Zhao A1 - John M Starr A1 - Mohammed Arfan Ikram A1 - David A Bennett A1 - Steven R Cummings A1 - Ian J Deary A1 - Tamara B Harris A1 - Sharon L R Kardia A1 - Thomas H Mosley A1 - Velandai K Srikanth A1 - Beverly G Windham A1 - Anne B Newman A1 - Jeremy D Walston A1 - Gail Davies A1 - Daniel S Evans A1 - Eline P Slagboom A1 - Luigi Ferrucci A1 - Douglas P Kiel A1 - Joanne M Murabito A1 - Atzmon, Gil KW - Genetics KW - GWAS AB - 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. VL - 9 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28077804?dopt=Abstract ER -