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Heritability and genome-wide association analyses of human gait suggest contribution of common variants

Citation

Adams, HHH and Verlinden, VJA and Callisaya, ML and van Duijn, CM and Hofman, A and Thomson, R and Uitterlinden, AG and Vernooij, MW and van der Geest, JN and Srikanth, V and Ikram, MA, Heritability and genome-wide association analyses of human gait suggest contribution of common variants, Journals of Gerontology. Series A: Biological Sciences and Medical Sciences, 71, (6) pp. 740-746. ISSN 1079-5006 (2016) [Refereed Article]

Copyright Statement

Copyright 2015 The Author

DOI: doi:10.1093/gerona/glv081

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 = 2.3010−8). 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.

Item Details

Item Type:Refereed Article
Keywords:gait, genome-wide association study, heritability
Research Division:Medical and Health Sciences
Research Group:Public Health and Health Services
Research Field:Epidemiology
Objective Division:Health
Objective Group:Specific Population Health (excl. Indigenous Health)
Objective Field:Health Related to Ageing
Author:Callisaya, ML (Dr Michele Callisaya)
Author:Thomson, R (Dr Russell Thomson)
Author:Srikanth, V (Dr Velandai Srikanth)
ID Code:102198
Year Published:2016 (online first 2015)
Web of Science® Times Cited:3
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-08-04
Last Modified:2017-11-03
Downloads:0

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