rs10483877 (VASH1-DT): VASH1 Blood Expression QTL

Key takeaways

• The ALT allele of rs10483877 is linked to reduced VASH1 expression in whole blood, with a p-value of 5.7e-170, among the most significant gene-expression signals on record
• Expression effects extend beyond blood to small intestine and immune cells, pointing to a broad multi-tissue footprint
• A nearby gene (ENSG00000259124) shows the opposite pattern, with increased expression in visceral fat, thyroid, peripheral nerve, and esophageal muscle when the ALT allele is present
• This locus was studied in a UK Biobank proteomics project measuring 1,463 blood proteins across 54,000+ participants
• No clinical disease associations or lifestyle factors are reported for this variant in the available evidence

What the research says

A proteomics genome-wide association study using UK Biobank data measured 1,463 blood circulating proteins in more than 54,000 participants and identified 4,248 associations between genetic variants and ratios of protein pairs (ratio quantitative trait loci, or rQTLs, meaning genetic signals detected by comparing protein levels against each other rather than in isolation). These rQTLs were 7.6-fold enriched in established protein-protein interactions, and the ratio-based approach increased total genetic signal discovery by 24.7% over standard analysis. Gene expression data from GTEx v11 (953 donors, FDR < 0.05) show that the ALT allele at rs10483877 (VASH1-DT) is associated with substantially reduced VASH1 expression in whole blood (p = 5.7e-170), small intestine terminal ileum (p = 2.2e-12), and EBV-transformed lymphocytes (p = 3.8e-13) GTEx Portal. The same ALT allele is associated with increased expression of ENSG00000259124 in visceral adipose tissue (omentum), thyroid, tibial nerve, and esophageal muscularis (p range: 2.6e-9 to 3.7e-14), and with reduced expression of ENSG00000259081 in whole blood (p = 1.3e-14) GTEx Portal.

Reported associations

• VASH1 expression - whole blood, small intestine terminal ileum, EBV-transformed lymphocytes: The ALT allele is associated with reduced VASH1 expression across all three tissues (p = 5.7e-170 in whole blood; p = 2.2e-12 in small intestine; p = 3.8e-13 in lymphocytes) GTEx Portal
• ENSG00000259124 expression - visceral adipose tissue, thyroid, tibial nerve, esophageal muscularis: The ALT allele is associated with increased expression across these four tissues (p range: 2.6e-9 to 3.7e-14) GTEx Portal
• ENSG00000259081 expression - whole blood: The ALT allele is associated with reduced expression (p = 1.3e-14) GTEx Portal

Evidence quality

The GTEx v11 eQTL data for rs10483877 is based on 953 donors analyzed at a stringent FDR < 0.05 threshold. The VASH1 whole-blood signal (p = 5.7e-170) is exceptionally strong relative to typical eQTL benchmarks. The accompanying UK Biobank proteomics study included more than 54,000 participants across 1,463 proteins, making it one of the largest proteomics GWASs reported to date; however, the provided study text does not explicitly confirm whether rs10483877 reached significance as a pQTL or rQTL in that analysis, so a direct protein-level association cannot be confirmed from the available evidence. No conflicting findings were present across the provided sources. Available evidence is limited to gene expression levels; no clinical outcomes or disease endpoints for this locus appear in the provided sources.

Tissue-specific expression effects

• VASH1: Reduced expression in whole blood, small intestine terminal ileum, and EBV-transformed lymphocytes when the ALT allele is present; the whole-blood effect is particularly strong GTEx Portal
• ENSG00000259124: Increased expression in visceral adipose tissue (omentum), thyroid, tibial nerve, and esophageal muscularis when the ALT allele is present GTEx Portal
• ENSG00000259081: Reduced expression in whole blood when the ALT allele is present GTEx Portal

Lifestyle considerations

No lifestyle considerations on file for this variant.