@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}
}
@article {8614,
	title = {GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium.},
	journal = {Aging Cell},
	volume = {15},
	year = {2016},
	month = {2016 10},
	pages = {792-800},
	abstract = {<p>Decline in muscle strength with aging is an important predictor of health trajectory in the elderly. Several factors, including genetics, are proposed contributors to variability in muscle strength. To identify genetic contributors to muscle strength, a meta-analysis of genomewide association studies of handgrip was conducted. Grip strength was measured using a handheld dynamometer in 27~581 individuals of European descent over 65~years of age from 14 cohort studies. Genomewide association analysis was conducted on ~2.7 million imputed and genotyped variants (SNPs). Replication of the most significant findings was conducted using data from 6393 individuals from three cohorts. GWAS of lower body strength was also characterized in a subset of cohorts. Two genomewide significant (P-value< 5~{\texttimes}~10(-8) ) and 39 suggestive (P-value< 5~{\texttimes}~10(-5) ) associations were observed from meta-analysis of the discovery cohorts. After meta-analysis with replication cohorts, genomewide significant association was observed for rs752045 on chromosome 8 (β~=~0.47, SE~=~0.08, P-value~=~5.20~{\texttimes}~10(-10) ). This SNP is mapped to an intergenic region and is located within an accessible chromatin region (DNase hypersensitivity site) in skeletal muscle myotubes differentiated from the human skeletal muscle myoblasts cell line. This locus alters a binding motif of the CCAAT/enhancer-binding protein-β (CEBPB) that is implicated in muscle repair mechanisms. GWAS of lower body strength did not yield significant results. A common genetic variant in a chromosomal region that regulates myotube differentiation and muscle repair may contribute to variability in grip strength in the elderly. Further studies are needed to uncover the mechanisms that link this genetic variant with muscle strength.</p>},
	keywords = {Adult, Aged, Chromatin Immunoprecipitation, Cohort Studies, Epigenesis, Genetic, Genome-Wide Association Study, Hand Strength, Humans, Molecular Sequence Annotation, Muscle Strength, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Reproducibility of Results},
	issn = {1474-9726},
	doi = {10.1111/acel.12468},
	author = {Amy M Matteini and Toshiko Tanaka and Karasik, David and Atzmon, Gil and Chou, Wen-Chi and John D Eicher and Andrew D Johnson and Alice M. Arnold and Michele L Callisaya and Gail Davies and Daniel S Evans and Holtfreter, Birte and Kurt Lohman and Kathryn L Lunetta and Mangino, Massimo and Albert Vernon Smith and Jennifer A Smith and Teumer, Alexander and Lei Yu and Dan E Arking and Aron S Buchman and Chibinik, Lori B and Philip L de Jager and Jessica Faul and Melissa E Garcia and Gillham-Nasenya, Irina and Gudnason, Vilmundur and Hofman, Albert and Hsu, Yi-Hsiang and Ittermann, Till and Lahousse, Lies and David C Liewald and Yongmei Liu and Lopez, Lorna and Fernando Rivadeneira and Rotter, Jerome I and Siggeirsdottir, Kristin and John M Starr and Thomson, Russell and Tranah, Gregory J and Andr{\'e} G Uitterlinden and V{\"o}lker, Uwe and V{\"o}lzke, Henry and David R Weir and Kristine Yaffe and Wei Zhao and Wei Vivian Zhuang and Zmuda, Joseph M and David A Bennett and Steven R Cummings and Ian J Deary and Luigi Ferrucci and Tamara B Harris and Sharon L R Kardia and Kocher, Thomas and Stephen B Kritchevsky and Psaty, Bruce M and Seshadri, Sudha and Timothy Spector and Velandai K Srikanth and Beverly G Windham and Zillikens, M Carola and Anne B Newman and Jeremy D Walston and Douglas P Kiel and Joanne M Murabito}
}
