rs11621961 (SERPINA10/SERPINA6): Aging decline variant
Key takeaways
- rs11621961 sits between the SERPINA10 and SERPINA6 genes and was identified in a large genome-wide study of how cognitive and physical function change with age.
- Baseline physical function is roughly 10 times more heritable than its rate of decline, a finding that points to two genetically distinct dimensions of aging.
- GTEx data show this variant's alternate allele is linked to reduced expression of the PPP4R4 gene in thyroid tissue.
- The evidence for this variant is early-stage; no confirmed per-variant effect size has been published in the available research.
Key takeaways
- rs11621961 sits between the SERPINA10 and SERPINA6 genes and was identified in a large genome-wide study of how cognitive and physical function change with age.
- Baseline physical function is roughly 10 times more heritable than its rate of decline, a finding that points to two genetically distinct dimensions of aging.
- GTEx data show this variant's alternate allele is linked to reduced expression of the PPP4R4 gene in thyroid tissue.
- The evidence for this variant is early-stage; no confirmed per-variant effect size has been published in the available research.
What the research says rs11621961 falls within a genomic locus containing SERPINA10 and SERPINA6. A genome-wide association study (GWAS) of UK Biobank participants investigated this region using longitudinal aging data, comparing genetic contributions to baseline cognitive and physical function against rates of age-related decline; that study found that baseline physical function and its rate of decline have markedly different heritability levels (approximately 31.38% for baseline versus approximately 3.15% for rate of decline), and that distinct genetic loci underlie each dimension. Expression quantitative trait locus (eQTL) data from GTEx separately show that the alternate allele at this position is associated with reduced expression of the PPP4R4 gene in thyroid tissue (slope -0.21, p=3.6e-5) GTEx Portal.
Reported associations
- Longitudinal cognitive and physical aging: This variant was identified in a genome-wide study of UK Biobank participants examining baseline cognitive and physical function and their rates of age-related decline over time.
- PPP4R4 expression in thyroid tissue: The alternate allele is associated with reduced expression of PPP4R4 in thyroid tissue (eQTL slope -0.21, p=3.6e-5) GTEx Portal.
Evidence quality The principal GWAS source is a large-scale UK Biobank study (Schoeler, Pingault, and Kutalik, 2025, Nature Communications) that used simulation-validated methods to evaluate statistical models of longitudinal change before running genome-wide scans, adding methodological rigor to the approach. The study authors explicitly note that selective participation and attrition in prospective biobank samples are important limitations for inference, as longitudinally assessed individuals may represent a healthier subset of an already healthy recruited sample. No PMID was available for this study, which limits inline citation. The GTEx eQTL result in thyroid tissue (p=3.6e-5) reflects a gene-regulation mechanism rather than a direct clinical outcome and should be interpreted as a pointer to potential biological pathway involvement, not a confirmed phenotypic finding. No specific per-variant effect size or significance threshold for rs11621961 is reported in the provided source material, and independent replication has not been documented in the available studies. Overall, evidence for this locus is preliminary.
Tissue-specific expression effects
- PPP4R4: The alternate allele at rs11621961 is linked to reduced expression of PPP4R4 in thyroid tissue; no other tissues reached significance in the available GTEx data GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What genes are near rs11621961?
rs11621961 sits in a genomic region between two genes called SERPINA10 and SERPINA6.
Is rs11621961 linked to aging or cognitive decline?
This variant was examined in a genome-wide study of longitudinal cognitive and physical function using UK Biobank data. No specific per-variant effect size is available in the published summary provided.
What does GTEx show for rs11621961?
GTEx expression data indicate that the alternate allele at rs11621961 is associated with reduced expression of the PPP4R4 gene in thyroid tissue. This is an eQTL finding reflecting gene regulation, not a direct clinical outcome.
How heritable is physical decline compared to baseline physical function?
In the UK Biobank study that examined this variant, baseline physical function showed roughly 31% heritability while the rate of physical decline showed only about 3%, suggesting these are genetically distinct aspects of aging.
What is the difference between baseline function and rate of decline in this research?
Baseline function refers to how capable someone is at a single point in time, while rate of decline measures how fast that capability changes over time. The UK Biobank study found these two aspects of aging have very different genetic architectures.