rs12202131 (TRIM40): Blood Cell Trait Variant

Key takeaways

• rs12202131 was identified in one of the largest blood cell genetics studies to date, covering 563,085 participants across 29 distinct blood cell traits.
• The ALT allele raises expression of HLA-H in brain cerebellum and cerebellar hemisphere, and in cultured fibroblasts, according to GTEx v11 data.
• Multiple nearby genes show increased expression in cultured fibroblasts, thyroid, and brain tissue.
• No lifestyle or drug response data specific to this variant are present in the available evidence.

What the research says rs12202131 was among the variants identified in a large-scale GWAS (genome-wide association study) integrating data from 563,085 European-ancestry participants to map genetic variation across 29 blood cell phenotypes PMID 32888494. The study discovered 5,106 new genetic associations and characterized the full genetic architecture of hematopoiesis (the process by which all blood cells are produced), covering variation from common to rare alleles PMID 32888494. GTEx v11 eQTL (expression quantitative trait locus) data show that the ALT allele is associated with increased expression of several nearby genes across multiple tissues, including brain and fibroblast cell lines GTEx Portal.

Reported associations

• Blood cell phenotypes (hematopoiesis): Identified as a variant associated with one or more of 29 blood cell traits in a GWAS of 563,085 European-ancestry participants; specific per-trait associations and per-variant effect sizes for rs12202131 are not itemized in the available study excerpt PMID 32888494.

Evidence quality The primary evidence comes from one large GWAS (n=563,085 European-ancestry participants) that is among the largest blood cell phenotype studies conducted to date PMID 32888494. The study included replication analyses comparing UK Biobank with the Million Veteran Program cohort. However, the specific p-value, odds ratio, and trait-level replication status for rs12202131 individually are not detailed in the provided study text, so the strength of evidence for this specific variant cannot be fully assessed from available materials. GTEx eQTL data (FDR < 0.05, 953 donors) provide functional supporting context but do not establish causal disease links.

Tissue-specific expression effects

• ENSG00000310496: The ALT allele is associated with increased expression in cultured fibroblasts and thyroid GTEx Portal.
• HLA-H: The ALT allele is associated with increased expression in brain cerebellum, brain cerebellar hemisphere, and cultured fibroblasts GTEx Portal.
• ENSG00000290870: The ALT allele is associated with increased expression in brain cerebellum and brain cerebellar hemisphere GTEx Portal.
• HCP5B: The ALT allele is associated with increased expression in brain cerebellum GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.