rs1190452 (EIF4E2): Blood Cell Genetics Variant

Key takeaways

• rs1190452 sits near EIF4E2, a gene that controls which cellular messages get translated into protein.
• A trans-ethnic study of over 746,000 people identified this variant in the context of blood cell trait genetics.
• In muscle and heart tissue, the variant is linked to reduced EIF4E2 expression, but it increases expression in the brain's caudate nucleus.
• The same variant also reduces expression of nearby genes PRSS56 and CHRND in skeletal muscle.

What the research says rs1190452 is a variant near the EIF4E2 gene (eukaryotic translation initiation factor 4E type 2, also called 4EHP), which encodes a cap-binding protein that competes with the primary translation initiation factor eIF4E to suppress translation of certain messenger RNAs. A trans-ethnic meta-analysis of 15 hematological traits - including red blood cell, white blood cell, and platelet measures - in 746,667 participants from 5 global populations (including 184,424 non-European individuals) identified 5,552 trait-variant associations at P<5x10^-9, with trans-ethnic fine-mapping producing 95% credible sets 30% smaller than those from European-only analyses. Expression quantitative trait locus (eQTL) data from GTEx, based on 953 tissue donors, links this variant to tissue-specific changes in EIF4E2 expression and three neighboring genes, with the direction of effect differing between muscle and heart versus brain. GTEx Portal

Reported associations

• Hematological traits: rs1190452 was catalogued in a trans-ethnic GWAS of 15 blood cell traits in 746,667 participants across 5 global populations; the specific blood cell trait linked to this exact variant is not stated in the available study text.
• EIF4E2 expression in skeletal muscle: The alternative allele is linked to reduced EIF4E2 expression in skeletal muscle. GTEx Portal
• EIF4E2 expression in heart: The alternative allele is linked to reduced expression in both atrial appendage and left ventricle cardiac tissues. GTEx Portal
• EIF4E2 expression in brain caudate: In contrast to muscle and heart, the alternative allele is linked to increased EIF4E2 expression in the caudate nucleus of the basal ganglia. GTEx Portal
• PRSS56 expression in skeletal muscle: The alternative allele is linked to reduced expression of PRSS56, a gene encoding a serine protease, in skeletal muscle. GTEx Portal
• CHRND expression in skeletal muscle: The alternative allele is linked to reduced expression of CHRND, which encodes a delta subunit of the nicotinic acetylcholine receptor (a muscle signaling protein), in skeletal muscle. GTEx Portal
• ENSG00000237126 expression: The alternative allele is linked to reduced expression of this locus in skeletal muscle and increased expression in esophageal mucosa. GTEx Portal

Evidence quality The GWAS evidence comes from a large and well-powered trans-ethnic meta-analysis published in Cell (2021) (n=746,667, including 184,424 non-European participants from 5 global populations) using a stringent significance threshold of P<5x10^-9. Replication was attempted in the Million Veteran Program cohort: of 88 tested associations, 85 showed consistent direction of effect (binomial P=6x10^-24), 83 were confirmed at FDR<5%, and 44 met Bonferroni-adjusted significance at P<6x10^-4. Trans-ethnic fine-mapping reduced 95% credible sets by approximately 30% relative to European-only analyses, improving localization of likely causal variants. The specific hematological trait tied to rs1190452 is not extractable from the available study text, which limits how precisely the GWAS association can be characterized here. The GTEx eQTL evidence is drawn from 953 tissue donors at FDR<0.05 and reflects tissue-level gene expression changes; eQTL associations describe a regulatory mechanism, not clinical outcomes. The opposing direction of EIF4E2 expression between muscle and heart versus brain caudate is a notable tissue-specific regulatory pattern and should be treated as preliminary until confirmed by follow-up functional work.

Tissue-specific expression effects

• EIF4E2: The alternative allele is linked to reduced expression in skeletal muscle and in both cardiac tissues examined (atrial appendage and left ventricle), but to increased expression in the brain's caudate nucleus (part of the basal ganglia). The opposing directions in muscle and heart versus brain suggest tissue-specific regulatory mechanisms. GTEx Portal
• ENSG00000237126: The alternative allele is linked to reduced expression in skeletal muscle and increased expression in esophageal mucosa. GTEx Portal
• PRSS56: The alternative allele is linked to reduced expression in skeletal muscle. GTEx Portal
• CHRND: The alternative allele is linked to reduced expression in skeletal muscle. GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.