rs113080727 (FAM124B): Aging Decline Genetics

Key takeaways

• rs113080727 sits in the intergenic region between USP21P1 and FAM124B, and was identified in a UK Biobank genome-wide scan of longitudinal aging phenotypes.
• The genetics of baseline function and the genetics of decline over time are largely separate, with different associated loci and very different heritabilities.
• Physical function heritability at baseline is roughly 31%, compared with only about 3% for the rate of physical decline, showing these are genetically distinct outcomes.
• Cognitive decline tracks closely with Alzheimer's disease genetic liability, while physical decline is more influenced by telomere length and bone mineral density.
• Evidence for this specific variant is preliminary; no independent replication is documented in the provided literature.

What the research says A 2025 genome-wide association study (GWAS - a scan of hundreds of thousands of genetic variants to find those statistically linked to a trait) in Nature Communications by Schoeler, Pingault, and Kutalik used longitudinally collected UK Biobank data to identify genetic contributors to cognitive and physical decline over time. The study demonstrated that baseline function and rate of decline are genetically distinct dimensions, with physical function baseline heritability estimated at 31.38% versus 3.15% for physical decline, and found that cognitive decline was substantially driven by Alzheimer's disease genetic liability (Mendelian Randomization effect gamma = 0.17) while physical decline was more influenced by telomere length and bone mineral density (each gamma = -0.05). The rs113080727 variant in the USP21P1 - FAM124B intergenic region was among the loci identified in these genome-wide scans, though per-variant effect sizes and exact phenotype assignment for this locus are not detailed in the available study excerpt.

Reported associations

• Longitudinal cognitive and/or physical aging decline: rs113080727 was surfaced in a genome-wide scan of longitudinal aging phenotypes drawn from UK Biobank participants with repeated assessments; the specific outcome trait and per-variant effect size are not available in the provided study text.

Evidence quality The source study (Schoeler, Pingault, Kutalik, Nature Communications 2025) used UK Biobank prospective data and modeled two-wave changes (baseline plus at least one follow-up) in cognitive and physical function, with three-wave data available for a smaller subset of participants. Baseline physical function heritability was estimated at 31.38% and decline heritability at 3.15%, and the study identified distinct genetic loci for each - for example, DUSP6 was reported as specific to physical decline. The authors explicitly flagged selective attrition as a concern, noting that longitudinal follow-up cohorts represent a healthier subset of an already health-selected recruited sample, which may affect generalizability of findings. No p-value or effect size specific to rs113080727 is available in the provided text. This variant has not been reported in additional independent studies in the provided literature, so evidence should be considered preliminary.

Lifestyle considerations No lifestyle considerations on file for this variant.