rs116275300 (GS1-279B7.1): Aging Decline GWAS Variant
Key takeaways
- This variant was flagged in a large-scale longitudinal genome-wide study of age-related cognitive and physical decline in UK Biobank participants.
- The associated genes, GS1-279B7.1 (a long non-coding RNA) and RNU7-183P (a small nuclear RNA pseudogene), are non-coding RNA loci whose specific roles in aging are not yet established.
- In testis tissue, the alternative allele is linked to reduced expression of TRMT1L, a gene involved in chemical modification of RNA molecules.
- Evidence for this specific variant remains preliminary, as no standalone effect size for rs116275300 was reported in the available study text.
Key takeaways
- This variant was flagged in a large-scale longitudinal genome-wide study of age-related cognitive and physical decline in UK Biobank participants.
- The associated genes, GS1-279B7.1 (a long non-coding RNA) and RNU7-183P (a small nuclear RNA pseudogene), are non-coding RNA loci whose specific roles in aging are not yet established.
- In testis tissue, the alternative allele is linked to reduced expression of TRMT1L, a gene involved in chemical modification of RNA molecules, according to GTEx v11 data.
- Evidence for this specific variant remains preliminary; no standalone effect size for rs116275300 was reported in the available study text.
What the research says A 2025 longitudinal genome-wide association study (GWAS, meaning a scan of hundreds of thousands of genetic variants across the genome) using UK Biobank data examined the genetic contributors to change in global cognitive and physical function over time, finding distinct heritability levels for baseline function versus rate of decline - for example, 31.38% versus 3.15% for physical function - and identifying trait-specific loci across the genome. In GTEx v11 data from 953 donors, the alternative allele of rs116275300 is associated with significantly reduced expression of TRMT1L (tRNA methyltransferase 1-like, a gene involved in chemical modification of RNA molecules) specifically in testis tissue, with an effect slope of -0.36 and p = 4.3e-6 GTEx Portal.
Reported associations
- Age-related cognitive and physical aging phenotypes (longitudinal GWAS): Identified in a UK Biobank GWAS examining change over time in global cognitive and physical function; the specific phenotype association and effect size for rs116275300 itself were not detailed in the available study text.
- TRMT1L expression in testis: The alternative allele is associated with reduced TRMT1L gene expression in testis tissue (effect slope -0.36, p = 4.3e-6, FDR < 0.05, n = 953 donors) GTEx Portal.
Evidence quality The source study (Schoeler et al., Nature Communications, 2025) used simulation-validated two-wave models of longitudinal change in UK Biobank participants and explicitly noted that participation bias and selective attrition represent meaningful limitations when making inferences from this non-representative prospective sample. The heritability estimates illustrate a key methodological point: genetic effects on aging depend heavily on whether one studies baseline function or rate of decline, with physical function showing 31.38% heritability at baseline but only 3.15% for the rate of decline itself. No specific p-value or effect size for rs116275300 appeared in the available study text, making it difficult to independently assess this variant's association strength or direction. The GTEx eQTL (expression quantitative trait locus, meaning a genetic variant that predicts gene expression levels) finding for TRMT1L in testis meets the standard FDR < 0.05 threshold across 953 donors; however, eQTL effects describe a molecular observation and do not on their own confirm a causal role in aging or any clinical outcome.
Tissue-specific expression effects
- TRMT1L: The alternative allele is linked to reduced expression specifically in testis; no other tissues reached significance in GTEx v11 data GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs116275300?
rs116275300 is a genetic variant located near the non-coding RNA genes GS1-279B7.1 and RNU7-183P. It was identified in a large UK Biobank genome-wide study examining how cognitive and physical function change with age.
What genes are associated with rs116275300?
The variant is located near GS1-279B7.1, a long non-coding RNA gene, and RNU7-183P, a small nuclear RNA pseudogene. In testis tissue, the alternative allele is also linked to reduced expression of TRMT1L, a gene involved in chemical modification of RNA molecules.
Is rs116275300 linked to cognitive decline?
This variant was identified in a 2025 UK Biobank longitudinal GWAS studying cognitive and physical aging decline. However, the specific trait association and effect size for rs116275300 were not reported in the available study text, so the nature and strength of any link remain unclear.
What does the TRMT1L gene do?
TRMT1L (tRNA methyltransferase 1-like) is a gene involved in the chemical modification of transfer RNA molecules, which play a role in how cells build proteins. In this context, the alternative allele of rs116275300 is associated with reduced TRMT1L expression specifically in testis tissue.
What is GS1-279B7.1?
GS1-279B7.1 is a long non-coding RNA gene, meaning it produces RNA that is not translated into protein. Its specific biological function is not yet well characterized, and its connection to aging or disease remains an open research question.