Expressive

rs12090149 (KCNK1): eQTL effects and COVID-19 GWAS

Key takeaways

  • rs12090149 is located near KCNK1, a gene encoding a two-pore domain potassium channel found in many tissues.
  • The alternate allele reduces expression of a nearby gene (ENSG00000287423) in ovary, two skin tissue types, and pituitary gland.
  • It also reduces KCNK1 expression specifically in adrenal gland tissue.
  • This locus appeared in a large COVID-19 GWAS study, though specific effect sizes for rs12090149 were not reported in the available study text.
  • All findings are population-level associations; no established clinical implications exist.

Key takeaways

  • rs12090149 is located near KCNK1, a gene encoding a two-pore domain potassium channel found in many tissues.
  • The alternate allele reduces expression of a nearby gene (ENSG00000287423) in ovary, two skin tissue types, and pituitary gland.
  • It also reduces KCNK1 expression specifically in adrenal gland tissue.
  • This locus appeared in a large COVID-19 GWAS study, though specific effect sizes for rs12090149 were not reported in the available study text.
  • All findings are population-level associations; no established clinical implications exist.

What the research says A COVID-19 GWAS using UK Biobank data analyzed up to 18,481 susceptibility cases across 65 genome-wide analyses to identify host genetic factors influencing COVID-19 phenotypes, tracking signals at suggestive significance (P < 10^-5) in addition to genome-wide significant hits at loci including 3p21.31 and ABO (Thibord et al., HGG Advances, 2022). Tissue-expression data from GTEx (v11, 953 donors, FDR < 0.05) show that the alternate allele of rs12090149 is linked to reduced expression of ENSG00000287423 in four tissues (ovary, two skin regions, and pituitary gland) and to reduced expression of KCNK1 (the potassium channel gene at this locus) in adrenal gland GTEx Portal.

Reported associations

  • COVID-19 phenotypes (context): The GRASP portal COVID-19 GWAS analyzed susceptibility (up to 18,481 cases), hospitalization (up to 3,260), severe outcomes (up to 1,244), and death (up to 1,104) in UK Biobank participants; no specific effect size or p-value for rs12090149 is reported in the available text (Thibord et al., HGG Advances, 2022).
  • Gene expression - ENSG00000287423 in ovary, skin, and pituitary: The alternate allele is associated with reduced expression in ovary (slope -0.42), sun-exposed lower leg skin (slope -0.36), non-sun-exposed suprapubic skin (slope -0.35), and pituitary gland (slope -0.25), where slope values are log2-normalized expression units GTEx Portal.
  • Gene expression - KCNK1 in adrenal gland: The alternate allele is associated with reduced KCNK1 expression in adrenal gland (slope -0.26, log2-normalized) GTEx Portal.

Evidence quality The COVID-19 GWAS (Thibord et al., HGG Advances, 2022) is a large analysis using UK Biobank data from up to 487,320 participants across multiple ancestry groups, with up to 18,481 susceptibility cases, 3,260 hospitalization cases, 1,244 severe outcome cases, and 1,104 deaths; however, the study text available here does not report specific significance or effect-size data for rs12090149, making it impossible to assess the strength or replication status of any COVID-19 signal at this locus from the provided evidence. The GTEx eQTL data (v11, 953 donors, cis-window) provide statistically robust signals meeting FDR < 0.05: ENSG00000287423 associations reach p = 9.5 x 10^-16 in sun-exposed skin, p = 4.0 x 10^-13 in non-sun-exposed skin, p = 4.1 x 10^-7 in ovary, and p = 1.6 x 10^-5 in pituitary; the KCNK1 adrenal signal reaches p = 1.5 x 10^-7 GTEx Portal. These eQTL findings establish that the variant influences gene expression levels in specific tissues, but eQTL effects are mechanistic observations and do not by themselves establish disease associations.

Tissue-specific expression effects

  • ENSG00000287423 (at the RNU4-77P locus): The alternate allele is associated with reduced expression in ovary, sun-exposed lower leg skin, non-sun-exposed suprapubic skin, and pituitary gland GTEx Portal.
  • KCNK1: The alternate allele is associated with reduced expression in adrenal gland tissue GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is KCNK1 and what does it do?

KCNK1 encodes a two-pore domain potassium channel involved in regulating the resting electrical potential of cells. It is expressed in multiple tissue types and belongs to a family of background potassium channels important for cellular excitability.

Is rs12090149 associated with COVID-19 risk?

This locus appeared in a large COVID-19 genome-wide association study using UK Biobank data with up to 18,481 cases, but specific significance or effect-size data for rs12090149 are not reported in the available study text. Any potential COVID-19 association for this variant remains unconfirmed.

What does the GTEx eQTL data mean for rs12090149?

An eQTL is a DNA variant that affects how much of a nearby gene is produced in a given tissue. GTEx data show the alternate allele of rs12090149 is linked to lower output of two genes across five tissues, but this is a molecular observation and does not directly indicate a disease risk.

What is RNU4-77P?

RNU4-77P is a pseudogene, meaning it resembles a functional small nuclear RNA gene in sequence but is not confirmed to produce a functional product. Its specific biological role is not well characterized.

Which tissues are affected by the gene expression changes linked to rs12090149?

GTEx data show the alternate allele is linked to reduced expression of a gene at the RNU4-77P locus in ovary, sun-exposed lower leg skin, non-sun-exposed suprapubic skin, and pituitary gland, and to reduced KCNK1 expression in adrenal gland.