rs113617295 (HCG20): Cognitive and Physical Aging
Key takeaways
- Identified in a large genome-wide study of how cognitive and physical function change over time in UK Biobank participants
- The alternate allele raises NRM gene expression in brain cortex, spinal cord, and six other tissues based on GTEx data from 953 donors
- The underlying GWAS used a two-wave longitudinal design that captures decline rate, not just snapshot function
- Cognitive and physical decline were found to have distinct genetic architectures, with physical decline having much lower heritability (~3%) than baseline physical function (~31%)
Key takeaways
- Identified in a large genome-wide study of how cognitive and physical function change over time in UK Biobank participants
- The alternate allele raises NRM gene expression in brain cortex, spinal cord, and six other tissues based on GTEx data from 953 donors
- The underlying GWAS used a two-wave longitudinal design that captures decline rate, not just snapshot function, which is methodologically distinct from most cross-sectional aging genetics studies
- Cognitive and physical decline were found to have distinct genetic architectures, with physical decline having much lower heritability (~3%) than baseline physical function (~31%)
What the research says A genome-wide association scan of longitudinal cognitive and physical decline in the UK Biobank (a large prospective British cohort) identified loci contributing to age-related change; the study found that baseline function and rate of decline have distinct heritabilities and different genetic contributors, and that cognitive decline was largely driven by Alzheimer's disease liability while physical decline was mostly impacted by telomere length and bone mineral density. GTEx v11 expression data from 953 donors shows that the alternate allele at this locus is consistently associated with increased expression of NRM across eight tissues, with effects ranging from tibial artery (slope +0.55, p=8.2e-14) up to cervical spinal cord (slope +0.93, p=1.7e-7) GTEx Portal.
Reported associations
- Longitudinal cognitive or physical aging decline: This locus was reported in a GWAS of age-related change in cognitive and physical function in UK Biobank participants; the provided study excerpt does not include the specific effect size or direction of association for this variant, so the magnitude of its contribution to aging decline cannot be assessed from available materials
- NRM gene expression (multiple tissues): The alternate allele is linked to increased NRM expression across brain cortex, cervical spinal cord, sigmoid colon, EBV-transformed lymphocytes, visceral adipose tissue, aorta, tibial nerve, and tibial artery GTEx Portal
Evidence quality The GWAS drew on UK Biobank longitudinal data with a two-wave design, used simulations to validate change models, and included LD-score regression and Mendelian Randomization follow-up analyses. Heritability estimates for the studied outcomes ranged from approximately 3.15% for the rate of physical decline to 31.38% for baseline physical function, indicating limited statistical power for discovering loci specifically affecting the rate of decline. The specific p-value and effect size for rs113617295 in the GWAS are not reported in the provided study excerpt, so the strength of this variant's GWAS association cannot be fully assessed from available materials; this should be treated as preliminary evidence of association. The GTEx eQTL evidence is based on 953 donors with p-values ranging from 8.2e-14 to 1.7e-7 across eight tissue types GTEx Portal, representing statistically strong and tissue-replicated expression effects that are consistent in direction across all eight tissues.
Tissue-specific expression effects
- NRM: The alternate allele is associated with increased expression of this gene across eight tissues, including brain cortex, cervical spinal cord, sigmoid colon, EBV-transformed lymphocytes, visceral adipose tissue, aorta, tibial nerve, and tibial artery; the largest effects are seen in cervical spinal cord (increased expression, p=1.7e-7) and brain cortex (increased expression, p=2.5e-11), with consistent increased expression also present in all peripheral tissue types tested GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What gene is associated with rs113617295?
rs113617295 is located at the HCG20 locus. It also functions as an expression quantitative trait locus (eQTL) for the NRM gene, meaning the variant influences how much NRM is expressed in multiple tissues including brain cortex and spinal cord.
What conditions is rs113617295 associated with?
Based on available research, this variant was reported in a genome-wide study of longitudinal cognitive and physical decline using UK Biobank data. Specific effect sizes and trait direction for this variant are not stated in the available study materials, so this association should be considered preliminary.
Which tissues does rs113617295 affect gene expression in?
GTEx expression data from 953 donors shows the alternate allele increases NRM gene expression in eight tissues: brain cortex, cervical spinal cord, sigmoid colon, EBV-transformed lymphocytes, visceral adipose tissue, aorta, tibial nerve, and tibial artery.
What is the NRM gene?
NRM is the gene whose expression is influenced by rs113617295 across multiple tissues. GTEx data from 953 donors shows the alternate allele consistently raises NRM gene activity, with the strongest effects observed in cervical spinal cord and brain cortex.
How was rs113617295 discovered?
This variant was identified through genome-wide association scanning of longitudinal cognitive and physical aging traits in the UK Biobank. The study used a two-wave design to measure change over time rather than just baseline function, providing a more precise look at the genetics of aging decline than cross-sectional studies.