title: Heritability and Genome-Wide Association Analyses of Human Gait Suggest Contribution of Common Variants.
abstract: Human gait is a complex neurological and musculoskeletal function, of which the genetic basis remains largely unknown. To determine the influence of common genetic variants on gait parameters, we studied 2,946 participants of the Rotterdam Study, a population-based cohort of unrelated elderly individuals. We assessed 30 gait parameters using an electronic walkway, which yielded seven independent gait domains after principal component analysis. Genotypes of participants were imputed to the 1,000 Genomes reference panel for generating genetic relationship matrices to estimate heritability of gait parameters, and for subsequent genome-wide association scans (GWASs) to identify specific variants. Gait domains with the highest age- and sex-adjusted heritability were Variability (h (2) = 61%), Rhythm (37%), and Tandem (32%). For other gait domains, heritability estimates attenuated after adjustment for height and weight. Genome-wide association scans identified a variant on 1p22.3 that was significantly associated with single support time, a variable from the Rhythm domain (rs72953990; N = 2,946; β [SE] = 0.0069 (0.0012), p = 2.30×10(-8)). This variant did not replicate in an independent sample (N = 362; p = .78). In conclusion, human gait has highly heritable components that are explained by common genetic variation, which are partly attributed to height and weight. Collaborative efforts are needed to identify robust single variant associations for the heritable parameters.
authors.affiliation: Department of Epidemiology and Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Hieab H H
authors.initials: HH
authors.lastname: Adams
authors.affiliation: Department of Epidemiology and.
authors.forename: Vincentius J A
authors.initials: VJ
authors.lastname: Verlinden
authors.affiliation: Stroke and Ageing Research Centre, Medicine, School of Clinical Sciences, Monash Medical Centre, Monash University, Melbourne, Australia. Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Michele L
authors.initials: ML
authors.lastname: Callisaya
authors.affiliation: Genetic Epidemiology Unit, Department of Epidemiology.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.affiliation: Department of Epidemiology and.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Russell
authors.initials: R
authors.lastname: Thomson
authors.affiliation: Department of Internal Medicine.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Department of Epidemiology and Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Meike W
authors.initials: MW
authors.lastname: Vernooij
authors.affiliation: Department of Neuroscience and.
authors.forename: Jos N
authors.initials: JN
authors.lastname: van der Geest
authors.affiliation: Stroke and Ageing Research Centre, Medicine, School of Clinical Sciences, Monash Medical Centre, Monash University, Melbourne, Australia. Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Velandai
authors.initials: V
authors.lastname: Srikanth
authors.affiliation: Department of Epidemiology and Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands. Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands. m.a.ikram@erasmusmc.nl.
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005684:Gait; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies
keywords: Gait; Genome-wide association study; Heritability