Expressive

rs1043483 (VARS2): Psoriasis Risk and Tissue Expression

Key takeaways

  • rs1043483 falls within a genome-wide significant psoriasis risk locus from a 472,819-person multi-ancestry study with 28,869 cases and 443,950 controls
  • The ALT allele consistently raises VARS2 expression across 8 tissues in GTEx v11 data from 953 donors, including skin, whole blood, heart, skeletal muscle, and adipose tissue
  • Psoriasis-associated genes from this study show genetic overlap with inflammatory bowel diseases and Crohn's disease
  • The psoriasis meta-analysis found 74 risk loci total, 32 of them newly discovered, and prioritized 164 likely causal genes
  • GTEx eQTL p-values for this variant reach as low as 4.7e-50 in whole blood and 9.0e-36 in sun-exposed skin

Key takeaways

  • rs1043483 falls within a genome-wide significant psoriasis risk locus from a 472,819-person multi-ancestry study with 28,869 cases and 443,950 controls
  • The ALT allele consistently raises VARS2 expression across 8 tissues in GTEx v11 data from 953 donors, including skin, whole blood, heart, skeletal muscle, and adipose tissue
  • Psoriasis-associated genes from this study show genetic overlap with inflammatory bowel diseases and Crohn's disease
  • The psoriasis meta-analysis found 74 risk loci total, 32 of them newly discovered, and prioritized 164 likely causal genes
  • GTEx eQTL p-values for this variant reach as low as 4.7e-50 in whole blood and 9.0e-36 in sun-exposed skin

What the research says A multi-ancestry GWAS meta-analysis (28,869 psoriasis cases, 443,950 controls across UK Biobank, FinnGen Biobank, and South Asia Biobank) identified this locus among 74 genome-wide significant psoriasis risk loci, 32 of which were novel; the analysis prioritized 164 likely causal genes and estimated that common variants together explain approximately 15% of psoriasis genetic risk. Independently, GTEx v11 data from 953 donors shows that the ALT allele here consistently increases VARS2 expression across 8 tissues, with the largest magnitude increase in pancreas and the most statistically significant signal in whole blood (p=4.7e-50) GTEx Portal. Gene-set analyses found positive genetic correlations between psoriasis-associated genes and autoimmune conditions including ulcerative colitis, inflammatory bowel diseases, and Crohn's disease.

Reported associations

  • Psoriasis susceptibility: this locus is among 74 genome-wide significant findings in a 472,819-person multi-ancestry meta-analysis; across all 74 loci, common variants account for an estimated 15% of psoriasis genetic risk
  • VARS2 expression - whole blood: ALT allele linked to increased expression (p=4.7e-50, n=953 GTEx donors) GTEx Portal
  • VARS2 expression - skeletal muscle: ALT allele linked to increased expression (p=6.7e-38) GTEx Portal
  • VARS2 expression - subcutaneous adipose tissue: ALT allele linked to increased expression (p=2.0e-37) GTEx Portal
  • VARS2 expression - sun-exposed skin (lower leg): ALT allele linked to increased expression (p=9.0e-36) GTEx Portal
  • VARS2 expression - non-sun-exposed skin (suprapubic): ALT allele linked to increased expression (p=1.9e-27) GTEx Portal
  • VARS2 expression - heart (left ventricle): ALT allele linked to increased expression (p=1.7e-27) GTEx Portal
  • VARS2 expression - heart (atrial appendage): ALT allele linked to increased expression (p=1.3e-25) GTEx Portal
  • VARS2 expression - pancreas: ALT allele linked to increased expression with largest slope magnitude across all assayed tissues (p=1.9e-25) GTEx Portal

Evidence quality The psoriasis association derives from one of the largest published psoriasis GWAS meta-analyses, drawing on three major biobanks across European, Finnish, and South Asian ancestry groups and applying genome-wide significance thresholds (p < 5x10-8) via MR-MEGA, a method specifically designed for multi-ancestry analysis. Because the full study text was not fully available for this entry, the specific per-locus p-value and odds ratio for this psoriasis association cannot be reported; individual effect sizes remain uncharacterized from the available material. Gene-drug interaction analysis in the psoriasis study identified overlaps between psoriasis-associated genes and targets of current psoriasis medications, with 76 potential drug repurposing targets suggested, though whether VARS2 specifically is among these targets is not determinable from the provided text. The GTEx eQTL data are extremely well-powered, with all 8 tissue associations clearing standard significance thresholds by several orders of magnitude; no conflicting tissue-expression signals are present in the provided data, though no independent replication data specific to this psoriasis locus is included in the provided material.

Tissue-specific expression effects

  • VARS2: the ALT allele is associated with increased VARS2 expression in all 8 tissues assayed in GTEx v11 (953 donors), including both cardiac chambers, sun-exposed and non-sun-exposed skin, skeletal muscle, subcutaneous adipose tissue, pancreas, and whole blood; the largest magnitude increase is in pancreas and the most statistically significant signal is in whole blood (p=4.7e-50) 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.

Screening

  • Regular dermatology screening for psoriasis High

    VARS2 rs1043483-T allele confers substantially elevated genetic predisposition to psoriasis; regular clinical surveillance enables early detection

    Establish routine dermatology check-ups; discuss screening frequency given genetic predisposition

Frequently asked questions

What is rs1043483 and which gene is it near?

rs1043483 is a genetic variant located near the VARS2 gene. GTEx data from 953 donors shows that people carrying the ALT version of this variant tend to have higher VARS2 expression in multiple tissues, including skin, blood, heart, and muscle.

Is rs1043483 linked to psoriasis?

Yes. A multi-ancestry genome-wide association study of 472,819 people identified rs1043483 within one of 74 genome-wide significant psoriasis risk loci. Psoriasis is a chronic immune-mediated disease affecting the skin and joints.

Which tissues show increased VARS2 expression with rs1043483?

According to GTEx v11 data from 953 donors, the ALT allele at rs1043483 is associated with increased VARS2 expression in whole blood, skeletal muscle, subcutaneous adipose tissue, sun-exposed and non-sun-exposed skin, both heart chambers, and the pancreas.

How reliable is the evidence linking rs1043483 to psoriasis?

The psoriasis association comes from a large multi-ancestry meta-analysis using genome-wide significance standards across 472,819 individuals from three major biobanks. The GTEx tissue-expression signals are extremely statistically robust across all 8 tissues. The specific p-value and odds ratio for this individual variant's psoriasis association were not available in the study excerpt used for this entry.

Are other autoimmune conditions associated with rs1043483?

The psoriasis GWAS found that psoriasis-associated genes as a group show positive genetic correlation with inflammatory bowel diseases, ulcerative colitis, and Crohn's disease. This is a group-level finding across the 74 loci identified in the study, not an association specific to this one variant.