rs117431025 (GOSR1): Physical Aging GWAS Variant
Key takeaways
- This variant was identified in a genome-wide study of how physical and cognitive function change over time in UK Biobank participants
- The genetic basis of baseline physical fitness and the rate of physical decline are largely separate, with baseline heritability around 31% versus around 3% for decline
- Physical decline at the population level shares genetic roots with bone mineral density and telomere length
- The alternative allele is linked to changed expression of multiple genes in thyroid tissue and one gene in testis tissue, based on GTEx data
Key takeaways
- This variant was identified in a genome-wide study of how physical and cognitive function change over time in UK Biobank participants
- The genetic basis of baseline physical fitness and the rate of physical decline are largely separate, with baseline heritability around 31% versus around 3% for rate of decline
- Physical decline at the population level shares genetic roots with bone mineral density and telomere length
- The alternative allele is linked to changed expression of multiple genes in thyroid tissue and one gene in testis tissue, according to GTEx population-level expression data
What the research says
A genome-wide association study (a method that scans hundreds of thousands of genetic variants to find statistical links with a trait across a large sample) examined longitudinal cognitive and physical aging in UK Biobank participants, finding that baseline function and the rate of accelerated decline have distinct genetic architectures. Physical function at baseline carried a heritability estimate (the proportion of variation in a trait attributable to genetic differences between people) of around 31%, compared to only around 3% for the rate of physical decline. Using Mendelian Randomization (a method that uses genetic variants as causal proxies to test whether one trait influences another), the study found physical decline was associated with bone mineral density (standardized effect gamma = -0.05) and telomere length (gamma = -0.05), while cognitive decline was largely driven by Alzheimer's disease liability (gamma = 0.17).
Reported associations
- Longitudinal physical and cognitive aging phenotypes: rs117431025 was identified in a genome-wide scan of age-related decline in UK Biobank participants, as reported by Schoeler, Pingault, and Kutalik in Nature Communications (2025); traits examined included grip strength, fitness levels, forced expiratory volume (a lung function measure), reaction time, and fluid intelligence; genetic loci for accelerated decline and for baseline function were found to be largely distinct
Evidence quality
The finding comes from a large prospective longitudinal UK Biobank study. Physical function at baseline showed heritability of approximately 31.38% versus approximately 3.15% for accelerated decline, indicating that decline-specific loci may carry smaller population-level effects. The authors identified methodological challenges: selective attrition (healthier participants more likely to complete follow-up, which can bias estimates), limited three-wave data availability, and birth cohort effects that can confound age-varying genetic associations. No PMID was provided in the supplied study metadata. GTEx eQTL (expression quantitative trait locus - a statistical association between a genetic variant and a gene's expression level in a tissue) data are from GTEx v11 (953 donors, FDR below 0.05), representing population-level expression effects rather than clinical outcomes.
Tissue-specific expression effects
- ENSG00000264007: the alternative allele at this locus is associated with increased expression in thyroid tissue GTEx Portal
- ENSG00000266876: the alternative allele is associated with increased expression in thyroid tissue GTEx Portal
- ENSG00000214719: the alternative allele is associated with reduced expression in thyroid tissue GTEx Portal
- ENSG00000290404: the alternative allele is associated with reduced expression in testis tissue GTEx Portal
- ANKRD13B: the alternative allele is associated with increased expression in thyroid tissue GTEx Portal
Lifestyle considerations
No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs117431025 associated with?
rs117431025 near GOSR1 was identified in a genome-wide study of longitudinal physical and cognitive aging in UK Biobank participants. The study examined traits including grip strength, fitness levels, lung function, reaction time, and fluid intelligence as markers of aging over time.
What does the GOSR1 gene region do?
GOSR1 is the gene at the chromosomal region of rs117431025. It was highlighted through a large genome-wide scan of age-related physical and cognitive decline using UK Biobank longitudinal data. The variant also influences expression of nearby genes including ANKRD13B in thyroid tissue.
Why do the genetics of baseline fitness differ from the genetics of physical decline?
A large UK Biobank study found that baseline physical function has heritability of around 31%, roughly ten times higher than the rate of physical decline at around 3%. This suggests the two traits are driven by largely separate genetic factors, so studies of current fitness levels alone may miss genes relevant to how quickly fitness changes with age.
Does rs117431025 affect gene expression in specific tissues?
Yes, GTEx data from 953 donors show this variant is associated with changed expression of five genes: three with increased expression and one with reduced expression in thyroid tissue, plus one gene with reduced expression in testis tissue.
Is the evidence for this variant strong?
The finding comes from a large longitudinal UK Biobank study published in Nature Communications in 2025. The authors note that selective attrition in follow-up samples and limited three-wave data are challenges for longitudinal GWAS, and independent replication would strengthen confidence in these findings.