rs12155739 (NCALD): Gait Speed Variant in Aging
Key takeaways
- rs12155739 near NCALD appeared as a suggestive candidate in one of the largest genetic studies of walking speed in older adults
- No single variant reached genome-wide significance in this study, including rs12155739 - the evidence is preliminary
- Gait speed is highly polygenic, meaning hundreds of small-effect variants likely contribute together
- Synaptic function and neuronal development pathways may be involved in gait speed genetics
Key takeaways
- rs12155739 near NCALD (neurocalcin delta) appeared as a suggestive candidate in one of the largest genetic studies of walking speed in older adults
- No single variant reached genome-wide significance in this study, including rs12155739 - the evidence is preliminary
- Gait speed is highly polygenic, meaning hundreds of small-effect variants likely contribute together
- Synaptic function and neuronal development pathways may be involved in gait speed genetics
What the research says A genome-wide meta-analysis of gait speed in 31,478 older adults from 17 cohorts of the CHARGE consortium identified 536 suggestive signals near 69 genes; rs12155739 near this locus is among the candidates from this analysis. No individual signal reached conventional genome-wide significance (p < 5x10^-8), and the authors concluded that more refined phenotypes or larger samples may be needed to isolate individual loci. Pathway analysis placed gait speed as a polygenic complex trait within five major biological networks, with subsequent expression analysis pointing toward synaptic function and neuronal development as potential mechanisms; findings were checked in an additional 2,588 older adults from four independent studies.
Reported associations
- Gait speed: rs12155739 at the NCALD locus was identified as one of 536 suggestive genome-wide signals in a meta-analysis of 31,478 older adults from 17 CHARGE consortium cohorts; no formal genome-wide significance was reached for this or any other locus in the study
Evidence quality Evidence for this variant is preliminary and should be interpreted cautiously. The signal comes from a single meta-analysis (primary n=31,478 from 17 cohorts; validation n=2,588 from 4 independent studies) and is classified as suggestive rather than genome-wide significant. The study explicitly reports that no genome-wide significant signals were identified, which - given the sample size exceeding 30,000 participants - underscores the highly polygenic nature of gait speed and the small expected effect size of any individual variant. No independent replication of the association at this locus is described in the available study text, and the authors note that larger samples or more refined phenotypes may be needed to confirm individual candidate loci.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
Is rs12155739 linked to walking speed?
The variant was identified as a suggestive candidate in a meta-analysis of gait speed in 31,478 older adults, but it did not reach formal genome-wide significance. The finding is considered preliminary and awaits independent replication.
What gene is rs12155739 near?
rs12155739 is located near NCALD, the neurocalcin delta gene. This region was flagged as a suggestive signal in a large genome-wide association study of gait speed in older adults.
Why did no variant reach significance in the gait speed GWAS?
The study found that gait speed is a highly polygenic trait, shaped by many genetic variants each with a very small effect. The authors noted that more refined physical function measures or larger sample sizes may be needed to identify individual loci clearly.
How strong is the evidence for rs12155739 and gait speed?
Evidence is weak and preliminary. The signal is one of 536 suggestive findings from a single meta-analysis, and no independent replication of this specific variant has been reported in the available study text.
What biological pathways might connect gait speed to genetics?
The study's pathway analysis implicated five major biological networks. Expression analysis specifically highlighted synaptic function and neuronal development pathways as likely contributors to genetic effects on gait speed.