rs116631966 (EVI5): Blood Cell Variant and eQTL

Key takeaways

• rs116631966 sits near EVI5 and was studied in a trans-ethnic genome-wide association study of 15 blood cell traits across 746,667 participants from 5 global populations.
• The ALT allele at this locus is linked to increased expression of the gene GFI1 in sun-exposed skin, non-sun-exposed skin, and subcutaneous adipose tissue, based on GTEx data from 953 donors.
• The same ALT allele is associated with increased expression of the gene DIPK1A in tibial artery and two esophageal tissue sites.
• Including non-European participants in the source blood cell study reduced fine-mapping uncertainty by 30% compared to European-only analyses, improving precision in identifying likely causal variants.

What the research says A trans-ethnic meta-analysis of 15 hematological traits (quantitative blood measurements including red cell, white cell, and platelet indices) in 746,667 participants from 5 global populations identified 5,552 trait-variant associations at P<5x10-9, with 71 novel associations not previously found in European-only analyses. GTEx v11 expression data from 953 donors (cis-window, FDR<0.05) shows the ALT allele at rs116631966 increases GFI1 expression in skin and adipose tissue GTEx Portal, and increases DIPK1A expression in tibial artery and esophageal tissues GTEx Portal.

Reported associations

• Hematological traits (study context): The blood cell GWAS (746,667 participants, 15 traits, 5 global populations) is the primary study linking rs116631966 at the EVI5 locus to blood cell biology; the specific hematological trait associated with this variant is not identified in the available study text excerpt.
• GFI1 gene expression: The ALT allele is associated with increased GFI1 expression in sun-exposed lower-leg skin (slope +0.53, p=1.6x10-5), non-sun-exposed suprapubic skin (slope +0.51, p=1.5x10-4), and subcutaneous adipose tissue (slope +0.46, p=1.0x10-4) GTEx Portal.
• DIPK1A gene expression: The ALT allele is associated with increased DIPK1A expression in tibial artery (slope +0.54, p=4.9x10-5), esophageal gastroesophageal junction (slope +0.33, p=5.7x10-7), and esophageal muscularis (slope +0.25, p=1.9x10-5) GTEx Portal.

Evidence quality The blood cell GWAS providing genomic context for the EVI5 locus analyzed up to 45 million autosomal variants in 746,667 individuals including 184,535 non-European participants from 5 global populations. Among 88 novel associations tested in the Million Veteran Program replication cohort, 85 showed directionally consistent effects (binomial P=6x10-24), 83 met a false discovery rate (FDR) below 5%, and 44 reached Bonferroni-corrected significance at P<6x10-4. GTEx v11 eQTL data comes from 953 donors at FDR<0.05; the most statistically robust individual signal across all tissues examined is DIPK1A in the esophageal gastroesophageal junction (p=5.7x10-7). Specific replication data for rs116631966 itself is not provided in the available study text, so the blood cell trait evidence quality for this variant cannot be independently assessed from the provided sources.

Tissue-specific expression effects

• GFI1: The ALT allele is associated with increased expression in both sun-exposed and non-sun-exposed skin, as well as subcutaneous adipose tissue; the direction of effect is consistent across all three tissue sites GTEx Portal.
• DIPK1A: The ALT allele is associated with increased expression in tibial artery and both queried esophageal sites (gastroesophageal junction and muscularis); the gastroesophageal junction carries the most statistically robust signal among all tissues examined for this variant GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.