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The complex genetics of gait speed: genome-wide meta-analysis approach
Dan Ben-Avraham1, David Karasik2,3, Joe Verghese4
1Department of Medicine and Genetics Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Aging
|January 13, 2017
Summary
Genetic factors influence late-life mobility, but this study found no genome-wide significant signals for gait speed in older adults. Further research with refined phenotypes is needed to uncover the genetic basis of aging gait speed.
Area of Science:
- Genetics
- Gerontology
- Epidemiology
Background:
- Genetic factors are increasingly recognized as contributors to mobility variation in aging.
- Understanding the genetic underpinnings of gait speed is crucial for promoting healthy aging.
Purpose of the Study:
- To systematically assess the contribution of genetic variation to gait speed in older individuals.
- To identify specific genes and pathways influencing gait speed through a large-scale meta-analysis.
Main Methods:
- Conducted a meta-analysis of genome-wide association studies (GWASs) for gait speed in over 31,000 older adults.
- Validated findings in an independent cohort of nearly 2,600 older adults.
- Performed network and expression quantitative trait loci (eQTL) analyses on candidate genetic signals.
Main Results:
- Identified 536 suggestive single nucleotide polymorphisms (SNPs) near 69 genes associated with gait speed.
- Gait speed was characterized as a polygenic complex trait within five major biological networks.
- Several SNPs showed significant associations with the expression of genes like PRSS16, WDSUB1, and PTPRT, suggesting roles in synaptic function and neuronal development.
Conclusions:
- Despite a large sample size, no genome-wide significant genetic signals for gait speed were identified.
- The genetic architecture of gait speed appears complex and potentially polygenic.
- More refined physical function phenotypes may be necessary to detect significant genetic associations for gait speed in aging populations.
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