@article {9172, title = {The complex genetics of gait speed: genome-wide meta-analysis approach.}, journal = {Aging (Albany NY)}, volume = {9}, year = {2017}, pages = {209-246}, abstract = {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.}, keywords = {Genetics, GWAS}, issn = {1945-4589}, doi = {10.18632/aging.101151}, author = {Ben-Avraham, Dan and Karasik, David and Joe Verghese and Kathryn L Lunetta and John D Eicher and Vered, Rotem and Deelen, Joris and Alice M. Arnold and Aron S Buchman and Toshiko Tanaka and Jessica Faul and Nethander, Maria and Myriam Fornage and Hieab H Adams and Amy M Matteini and Michele L Callisaya and Albert Vernon Smith and Lei Yu and Philip L de Jager and Denis A Evans and Gudnason, Vilmundur and Hofman, Albert and Pattie, Alison and Corley, Janie and Lenore J Launer and David S Knopman and Parimi, Neeta and Stephen T Turner and Bandinelli, Stefania and Beekman, Marian and Gutman, Danielle and Sharvit, Lital and Simon P Mooijaart and David C Liewald and Jeanine J Houwing-Duistermaat and Ohlsson, Claes and Moed, Matthijs and Vincent J Verlinden and Mellstr{\"o}m, Dan and Jos N van der Geest and Karlsson, Magnus and Dena G Hernandez and McWhirter, Rebekah and Yongmei Liu and Thomson, Russell and Tranah, Gregory J and Andr{\'e} G Uitterlinden and David R Weir and Wei Zhao and John M Starr and Mohammed Arfan Ikram and David A Bennett and Steven R Cummings and Ian J Deary and Tamara B Harris and Sharon L R Kardia and Thomas H Mosley and Velandai K Srikanth and Beverly G Windham and Anne B Newman and Jeremy D Walston and Gail Davies and Daniel S Evans and Eline P Slagboom and Luigi Ferrucci and Douglas P Kiel and Joanne M Murabito and Atzmon, Gil} }