Expressive

rs11227299 (OVOL1 / AP5B1): Brain and thyroid eQTL

Key takeaways

  • rs11227299 sits near AP5B1 (a cellular trafficking protein) and OVOL1 (a transcription factor involved in cell development)
  • The alternate allele increases OVOL1 expression in three brain regions including the cerebellum and cerebral cortex
  • The same allele increases MAP3K11 expression in the thyroid, esophagus, tibial artery, and tibial nerve
  • This locus was analyzed in a Korean biobank GWAS of 153,950 individuals studying 36 quantitative traits
  • These are gene-expression signals from population tissue data, not direct indicators of disease risk

Key takeaways

  • rs11227299 sits near two genes: AP5B1 (a subunit of the AP-5 late-endosomal vesicle trafficking complex) and OVOL1 (a zinc-finger transcription factor involved in cell differentiation)
  • The alternate allele is linked to increased OVOL1 expression in three brain regions: the cerebellum, cerebellar hemisphere, and cerebral cortex
  • The same allele is independently linked to increased MAP3K11 (a cell-stress signaling kinase) expression in the thyroid gland, two segments of the esophagus, the tibial artery, and the tibial nerve
  • This locus was analyzed in a genome-wide association study of 153,950 Korean individuals examining 36 quantitative traits across metabolic, hormonal, hematological, and cardiovascular domains
  • The gene-expression signals come from population-level tissue data and describe molecular correlations, not direct disease outcomes

What the research says A genome-wide association study of 153,950 Korean individuals in the Korean Cancer Prevention Study-II (KCPS2) Biobank analyzed 36 quantitative traits including anthropometric, metabolic, liver, thyroid, kidney, hematological, and cardiovascular measures, identifying 301 previously unreported loci within the KCPS2 cohort alone, with an additional 4,588 loci discovered through subsequent meta-analysis with Korean, Japanese, Taiwanese, and UK Biobank cohorts. Gene-expression data from GTEx v11 (953 donors, cis-eQTL window, FDR<0.05) shows the alternate allele at this locus is linked to substantially increased OVOL1 expression across three brain regions, with effect sizes of approximately 0.71 to 0.75 log2 units per allele copy GTEx Portal. The same allele is independently associated with increased MAP3K11 expression across five tissue types spanning the esophagus, thyroid, artery, and peripheral nerve, with effect sizes of approximately 0.26 to 0.36 log2 units per allele copy GTEx Portal.

Reported associations

  • OVOL1 expression in brain regions (eQTL): The alternate allele is associated with roughly 0.75 log2-unit higher OVOL1 expression per allele copy in the cerebellum (p=1.3e-21) and cerebellar hemisphere (p=1.2e-25), and roughly 0.71 log2 units higher in the cerebral cortex (p=4.3e-15), based on GTEx v11 data from 953 donors GTEx Portal
  • MAP3K11 expression across multiple tissues (eQTL): The alternate allele is associated with increased MAP3K11 expression per allele copy in the thyroid (+0.36 log2 units, p=4.5e-35), esophageal gastroesophageal junction (+0.36 log2 units, p=7.6e-25), esophageal muscularis (+0.33 log2 units, p=1.6e-32), tibial artery (+0.32 log2 units, p=3.3e-38), and tibial nerve (+0.26 log2 units, p=1.0e-31) GTEx Portal
  • Quantitative traits in Korean individuals: This locus was among those analyzed in a GWAS of 36 quantitative traits in 153,950 Korean participants from the KCPS2 Biobank, a study that identified 301 previously unreported genetic loci; specific per-variant effect sizes and trait-level phenotypic associations for rs11227299 are not specified in the available study summary

Evidence quality The eQTL associations from GTEx v11 carry extremely strong statistical support, with p-values as low as 3.3e-38 for MAP3K11 in tibial artery and 1.2e-25 for OVOL1 in the cerebellar hemisphere, all passing FDR<0.05 thresholds in a 953-donor dataset. The underlying GWAS (n=153,950) used a linear mixed model (SAIGE) with age, sex, 10 principal components, and SNP array as covariates; median genomic inflation factor (lambda_GC 1.23) and LDSC intercept (1.04) are consistent with well-controlled analyses without marked population stratification. The study authors note that over 90% of prior GWAS participants come from European ancestry samples, and that East Asian biobanks such as KCPS2 are necessary to identify population-specific or enriched associations; this limits direct cross-ancestry replication evidence for associations discovered in KCPS2. A central limitation for this entry is that specific phenotypic associations and effect sizes for rs11227299 at the trait level are not detailed in the available portions of the KCPS2 study, and independent replication of this variant's GWAS signal in separate cohorts is not confirmed in the provided literature.

Tissue-specific expression effects

  • OVOL1: The alternate allele is linked to increased expression in three brain regions - cerebellum, cerebellar hemisphere, and cerebral cortex - with highly consistent effect sizes of 0.71 to 0.75 log2 units per allele and p-values below 5e-15 across all three regions GTEx Portal
  • MAP3K11: The alternate allele is linked to increased expression across five tissue types spanning two esophageal regions (gastroesophageal junction and muscularis), the thyroid gland, the tibial artery, and the tibial nerve, with effect sizes of 0.26 to 0.36 log2 units per allele and p-values reaching as low as 3.3e-38 in tibial artery 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.

Diet

  • high-purine foods Moderate

    Purine metabolism produces uric acid; high dietary purine intake increases serum uric acid and gout risk

    Limit red meat and organ meats to less than 2 times per week; avoid high-purine seafood like anchovies and shellfish

Lifestyle

  • alcohol, especially beer Moderate

    Alcohol inhibits uric acid excretion by kidneys; beer contains purines that elevate uric acid

    Limit beer to less than 1 drink per week; spirits to occasional use only

  • daily water intake for uric acid clearance Moderate

    Increased fluid intake promotes uric acid excretion via kidneys, reducing serum uric acid levels

    Drink 2-3 liters of water daily, distributed throughout waking hours

  • maintain healthy body weight Moderate

    Obesity is associated with elevated serum uric acid and increased risk of gout attacks

    Target BMI 18.5-25; if overweight, aim for 5-10 percent weight loss over 3-6 months

Screening

  • baseline serum uric acid and gout risk assessment Moderate

    Genetic risk for gout warrants early assessment of serum uric acid levels and rheumatologic consultation

Frequently asked questions

What is the OVOL1 gene and what does it do?

OVOL1 (Ovo-Like Transcription Repressor 1) is a zinc-finger transcription factor, meaning it is a protein that controls when and where other genes are switched on or off. It plays a role in cell differentiation, particularly in epithelial tissues, and is also expressed in brain tissue based on GTEx data.

What does rs11227299 affect?

Based on GTEx v11 tissue expression data from 953 donors, the alternate allele of rs11227299 is associated with increased OVOL1 expression in three brain regions and increased MAP3K11 expression in the thyroid, esophagus, arteries, and peripheral nerves. This locus was also analyzed in a Korean GWAS of 36 quantitative traits, though specific phenotypic associations for this variant are not detailed in available study summaries.

What is MAP3K11 and why is it relevant to this variant?

MAP3K11, also known as MLK3, is a mitogen-activated protein kinase involved in cellular stress-response and inflammation-related signaling pathways. GTEx data shows that rs11227299 acts as an expression QTL for MAP3K11 in multiple tissues, correlating with how much of this protein is produced, though this is a mechanistic finding, not a confirmed disease association.

Is rs11227299 specific to East Asian or Korean populations?

The primary GWAS data cited here comes from 153,950 Korean individuals, and the study authors emphasize that over 90% of prior GWAS participants come from European ancestry samples, making East Asian biobank findings especially important. Whether this specific variant's associations replicate in European or other ancestry groups is not confirmed by the provided studies.