rs12142086 (IKBKE): Skin and Esophagus Expression
Key takeaways
- rs12142086 reduces IKBKE expression in sun-exposed skin, non-sun-exposed skin, and esophagus mucosa
- The effect extends to neighboring gene IKBKE-AS1 and a third gene (ENSG00000261000) in skin
- P-values in skin tissue reach 3.5e-118, indicating highly robust signals from 953 donors in GTEx v11
- Large-scale blood cell research covering 563,085 participants has mapped variant-trait associations in hematopoietic gene regions
Key takeaways
- rs12142086 is associated with reduced expression of IKBKE in both sun-exposed and non-sun-exposed skin, and in esophagus mucosa
- A neighboring gene, IKBKE-AS1, also shows reduced expression in the same tissue types
- A third gene in this region (ENSG00000261000) shows reduced expression specifically in skin
- The expression effects are statistically robust, with p-values reaching 3.5e-118 in skin tissue from GTEx v11 data covering 953 donors
What the research says GTEx v11 eQTL (expression quantitative trait locus - a variant that influences how much RNA a gene produces in a specific tissue) data from 953 donors shows that rs12142086 substantially reduces IKBKE expression in non-sun-exposed skin (p=1.6e-112), sun-exposed skin (p=3.5e-118), and esophagus mucosa (p=3.1e-79) GTEx Portal. The same variant also reduces expression of IKBKE-AS1, a neighboring gene, across the same three tissues, and reduces expression of a third gene (ENSG00000261000) in both skin tissue types GTEx Portal. A genome-wide association study (GWAS - a population-scale analysis that scans the full genome to link genetic variants to traits or conditions) of 29 blood cell phenotypes in 563,085 European ancestry participants characterized the genetic architecture of hematopoiesis (blood cell production) across the genome, identifying 5,106 new variant-trait associations.
Reported associations
- IKBKE expression: reduced in non-sun-exposed skin (slope -0.74, p=1.6e-112), sun-exposed skin (slope -0.65, p=3.5e-118), and esophagus mucosa (slope -0.55, p=3.1e-79) GTEx Portal
- IKBKE-AS1 expression: reduced in sun-exposed skin (slope -0.61, p=2.5e-64), non-sun-exposed skin (slope -0.58, p=2.9e-57), and esophagus mucosa (slope -0.36, p=8.0e-27) GTEx Portal
- ENSG00000261000 expression: reduced in non-sun-exposed skin (slope -0.62, p=1.2e-26) and sun-exposed skin (slope -0.54, p=3.5e-24) GTEx Portal
- Blood cell phenotypes (broad context): a GWAS of 29 blood traits in 563,085 participants identified 5,106 new genetic variant associations in hematopoietic regions; specific association of rs12142086 with a blood cell phenotype is not detailed in the available study text
Evidence quality The eQTL evidence from GTEx v11 is statistically robust, drawing on 953 donors with cis-window analysis at a false discovery rate (FDR) below 5%, with p-values ranging from 3.5e-24 to 3.5e-118 across the eight tissue-gene pairs for this variant GTEx Portal. The blood cell trait GWAS (Vuckovic et al., Cell, 2021) included 563,085 European ancestry participants and identified 5,106 new associations across 29 phenotypes, offering population-level context for genetic variants in hematopoietic gene regions; however, specific association data for rs12142086 is not present in the available study excerpt. GTEx eQTL signals represent statistical associations between a variant and local gene expression levels, not causal proof, and downstream phenotypic consequences of reduced expression in skin or esophagus tissue are outside the scope of the available evidence.
Tissue-specific expression effects
- IKBKE: reduced expression in non-sun-exposed skin (suprapubic), sun-exposed skin (lower leg), and esophagus mucosa; the largest effect is in non-sun-exposed skin GTEx Portal
- IKBKE-AS1: reduced expression in sun-exposed skin, non-sun-exposed skin, and esophagus mucosa GTEx Portal
- ENSG00000261000: reduced expression in non-sun-exposed skin and sun-exposed skin 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
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eosinophil percentage High
The C allele is associated with increased eosinophil percentage, suggesting baseline measurement and periodic monitoring to establish reference range and detect elevations.
CBC with differential at baseline and annually if normal; more frequently if abnormal
Discuss with your doctor
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eosinophil genetic predisposition and baseline High
Genetic association with increased eosinophils warrants clinical interpretation, as elevated eosinophils can indicate allergies, infections, or immune conditions requiring attention.
Bring findings to primary care visit for context and baseline establishment
Frequently asked questions
What does rs12142086 do?
Based on GTEx v11 data from 953 donors, rs12142086 is associated with reduced expression of the IKBKE gene in skin and esophagus tissue. The effect also extends to two neighboring genes, IKBKE-AS1 and ENSG00000261000, particularly in skin.
Which tissues are affected by rs12142086?
GTEx v11 data shows effects in three tissue types: non-sun-exposed skin (suprapubic), sun-exposed skin (lower leg), and esophagus mucosa. The strongest effects are seen in skin, where p-values fall below 1e-110.
Is rs12142086 linked to blood cell traits?
A large-scale study of 29 blood cell traits in over 563,000 participants characterized genetic variants across hematopoietic regions. Whether rs12142086 is specifically associated with a blood cell phenotype is not specified in the available study data.
What is IKBKE-AS1?
IKBKE-AS1 is a gene located adjacent to IKBKE. Like its neighbor, IKBKE-AS1 expression is reduced in skin and esophagus tissues when rs12142086 is present, based on GTEx v11 data from 953 donors.
How strong is the evidence for rs12142086 expression effects?
The GTEx v11 evidence is statistically very strong, with p-values reaching as low as 3.5e-118 in sun-exposed skin for IKBKE expression. The data comes from 953 donors with false discovery rate-controlled cis-window analysis, making these reproducible and robust signals.