rs115355186 (PRKG2): Physical Aging GWAS

Key takeaways

• rs115355186 maps to a genomic region containing the PRKG2 gene and the nearby RNU5A-2P pseudogene (a non-functional copy of a gene).
• This variant was identified in the context of a large genome-wide association study (GWAS) of physical and cognitive aging using longitudinal UK Biobank data.
• The genetics of physical function measured at a single time point and the genetics of how quickly physical function declines over time are largely distinct: baseline heritability is 31.38% versus only 3.15% for accelerated decline.
• Bone mineral density (BMD) and telomere length each show an independent negative influence on the rate of physical decline, with standardized Mendelian Randomization effects of -0.05 each.
• Specific effect sizes for rs115355186 individually are not reported in the available excerpt of the source study.

What the research says A genome-wide association study (GWAS) using longitudinally curated UK Biobank data examined the genetic basis of both baseline levels and rates of change in cognitive and physical functioning, finding the two aging dimensions to have distinct genetic architectures driven by different upstream factors. Physical function measured at baseline showed 31.38% heritability, while accelerated physical decline over time showed only 3.15% heritability; Mendelian Randomization analyses (a method that uses genetic variants as natural experiments to test causal effects, reducing confounding from lifestyle and environment) found that genetically predicted lower BMD and shorter telomere length each independently predicted faster physical decline (standardized effect gamma = -0.05 each). Cognitive decline was found to be largely driven by genetic liability to Alzheimer's disease (standardized Mendelian Randomization effect gamma = 0.17), indicating that cognitive and physical aging share little common genetic architecture.

Reported associations

• Physical function decline: The PRKG2 and RNU5A-2P locus was identified in a genome-wide scan of longitudinal physical aging traits in UK Biobank participants; the specific effect size (beta coefficient, odds ratio, or p-value) for rs115355186 is not available in the provided study excerpt.
• Physical versus cognitive aging specificity: The study found little overlap between the genetic factors driving cognitive decline and those driving physical decline, consistent with the study's finding that the two aging dimensions have largely distinct genetic architectures.

Evidence quality The source study used the UK Biobank, a large prospective cohort with repeated participant assessments, and applied simulation-validated two-wave models of change prior to genome-wide scanning. Analyses were supplemented by LD-score regression (a statistical method to estimate trait heritability and genetic correlation from GWAS summary statistics) and Mendelian Randomization. The study was published in Nature Communications in 2025, but no PubMed identifier (PMID) was available in the provided metadata, limiting inline citation. The specific statistical evidence for rs115355186 - its p-value, beta coefficient, or confidence interval - is not present in the excerpt provided, which covers only the study introduction. The authors acknowledge that selective attrition (healthier individuals being more likely to complete follow-up visits) may bias findings toward a healthier-than-average population, limiting generalizability. Evidence for this specific variant should be considered preliminary until full results are published and independently replicated.

Lifestyle considerations No lifestyle considerations on file for this variant.