Expressive

rs10774625 (ATXN2): Tissue Expression Effects

Key takeaways

  • This variant reduces ALDH2 gene activity in esophagus lining, skin, and tibial artery.
  • The same variant increases NAA25 expression in two cerebellar brain regions.
  • ADAM1B in heart tissue and TMEM116 in colon tissue are also affected.
  • These are gene expression effects, not direct measures of disease risk.
  • No GWAS disease associations were reported for this variant in the available literature.

Key takeaways

  • This variant reduces ALDH2 gene activity in esophagus lining, skin, and tibial artery.
  • The same variant increases NAA25 expression in two cerebellar brain regions.
  • ADAM1B in heart tissue and TMEM116 in colon tissue are also affected by this locus.
  • These are gene expression effects (eQTLs), not direct measures of disease risk.
  • No GWAS disease associations were reported for this variant in the available literature.

What the research says None of the provided GWAS studies specifically report associations for rs10774625. Gene expression data from GTEx v11 (953 donors, cis-window, FDR<0.05) shows that the alternate allele at this locus is linked to reduced ALDH2 expression across esophagus mucosa, skin, and tibial artery, alongside increased NAA25 expression in cerebellum and cerebellar hemisphere GTEx Portal. The locus also shows tissue-specific increases in ADAM1B expression in heart atrial appendage and TMEM116 expression in colon sigmoid GTEx Portal.

Reported associations

  • No disease or trait associations for rs10774625 were specifically identified in the provided GWAS literature, which covered large-scale analyses of circulating fatty acids, amino acids, metabolic biomarkers, fat distribution, and age-related macular degeneration.

Evidence quality Available evidence is limited to eQTL data from GTEx v11 (n=953 donors). All reported effects pass FDR<0.05 within a cis-window. The strongest signal is ALDH2 reduction in esophagus mucosa (p=2.0e-13), followed by non-sun-exposed suprapubic skin (p=3.8e-10), sun-exposed lower leg skin (p=1.0e-11), and tibial artery (p=2.4e-7). NAA25 expression increases in cerebellar hemisphere (p=2.3e-5) and cerebellum (p=2.0e-4) are well-supported. The ADAM1B heart signal (p=3.5e-5) and TMEM116 colon signal (p=5.0e-5) are weaker. None of the large-scale GWAS studies in the provided literature - covering up to 239,268 European participants for circulating fatty acids, up to 136,016 participants for metabolic biomarkers, and 635,969 participants across diverse populations - specifically name this variant in their reported findings. Evidence for clinical relevance is absent from the provided literature; the current data describes biological mechanism at the gene expression level only.

Tissue-specific expression effects

  • ALDH2: Reduced expression in esophagus mucosa, non-sun-exposed suprapubic skin, sun-exposed lower leg skin, and tibial artery; esophagus mucosa shows the most statistically robust reduction (p=2.0e-13) GTEx Portal.
  • ADAM1B: Increased expression in heart atrial appendage tissue GTEx Portal.
  • TMEM116: Increased expression in colon sigmoid tissue GTEx Portal.
  • NAA25: Increased expression in brain cerebellum and cerebellar hemisphere tissue GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Lifestyle context

Concrete actions anchored to the cited research. We do not prescribe, we describe.

Bloodwork

  • Fasting glucose for diabetes screening Moderate

    ATXN2 variant affects RBC traits, artificially elevating HbA1c independent of glucose control; fasting glucose is more reliable.

    Use fasting glucose (threshold >= 7 mmol/L) as primary diabetes screening; do not rely solely on HbA1c.

Diet

  • Purine-rich foods and alcohol High

    ATXN2 region variants strongly increase gout risk via uric acid metabolism; dietary purines and alcohol increase serum urate.

    Limit red meat, organ meats, anchovies, sardines, and beer; favor poultry, legumes, and low-fat dairy.

Discuss with your doctor

  • Chronic pain susceptibility and prevention Moderate

    ATXN2 region variants strongly associated with chronic pain susceptibility across multiple pain phenotypes and anatomical sites.

    Discuss pain prevention strategies, physical therapy, ergonomics, and early intervention thresholds with healthcare provider.

Lifestyle

  • Achieve healthy body weight Moderate

    Overweight and obesity increase serum uric acid; weight loss reduces gout risk.

    Target BMI 18.5-25 through balanced diet and regular physical activity.

  • Adequate hydration Moderate

    Higher fluid intake lowers serum uric acid concentration and reduces gout attack frequency.

    Drink 2.5-3 liters of water daily, more on exercise days or in hot climates.

Screening

  • Blood pressure monitoring Moderate

    ATXN2 region variants associated with wider retinal venules, a microvascular marker of hypertension and coronary artery disease risk.

    Check blood pressure annually; more frequently if above 120/80 mmHg.

  • Cardiovascular disease risk assessment Moderate

    ATXN2 region variants associated with retinal vascular changes and coronary artery disease risk; baseline assessment informs future monitoring.

    Obtain lipid panel and baseline ECG; consider repeat assessment every 3-5 years or per provider guidelines.

Frequently asked questions

What does rs10774625 do?

rs10774625 is a genetic variant that influences how actively several nearby genes are expressed in specific body tissues. It reduces ALDH2 gene activity in esophagus lining and skin, and increases NAA25 activity in brain cerebellar tissue.

What gene is rs10774625 associated with?

rs10774625 is located near the ATXN2 gene and also affects the activity levels of four other genes: ALDH2 (reduced in esophagus and skin), NAA25 (increased in brain), ADAM1B (increased in heart), and TMEM116 (increased in colon).

Is rs10774625 linked to any diseases?

The scientific literature reviewed for this entry does not report specific disease associations for rs10774625. The available data describes changes in gene expression levels in specific tissues, which is a different type of evidence than direct disease risk association.

What tissues are affected by rs10774625?

Gene expression data shows this variant affects ALDH2 activity in esophagus mucosa, sun-exposed and non-sun-exposed skin, and tibial artery, as well as NAA25 in brain cerebellum and cerebellar hemisphere, ADAM1B in heart atrial appendage, and TMEM116 in colon sigmoid.

What is an eQTL and why does it matter?

An eQTL (expression quantitative trait locus) is a genetic variant associated with differences in how actively a gene produces its protein product in a given tissue. Identifying eQTLs helps researchers understand the biological pathways through which genetic variants may influence health outcomes.