Expressive

rs11627901 (PPP4R3A/CATSPERB): Blood Traits Variant

Key takeaways

  • Identified in a blood cell genetics study of over 563,000 people, one of the largest of its kind
  • The alternate allele is linked to higher CCDC88C gene activity in multiple brain regions and the liver
  • A nearby gene shows lower activity in cerebellar and cingulate brain regions for carriers of the alternate allele
  • Functional genomics methods boosted detection power for significant loci by 9-38 percent in the supporting analysis
  • Specific blood cell trait effect sizes for this locus were not reported in the available study materials

Key takeaways

  • Identified in a genome-wide blood cell study of over 563,000 people, one of the largest genetic analyses of hematopoiesis (blood cell production) to date
  • The alternate allele is linked to increased CCDC88C gene activity in multiple brain regions and the liver
  • A nearby gene (ENSG00000300783) shows reduced activity in cerebellar and cingulate brain regions in carriers of the alternate allele
  • Functional genomics methods improved detection power for genome-wide significant loci by 9-38 percent in the supporting analysis
  • Specific blood cell trait effect sizes for this locus were not available in the provided study materials

What the research says rs11627901, in the PPP4R3A - CATSPERB locus, was identified in a large-scale genome-wide association study (GWAS) integrating UK Biobank and international cohort data for 563,085 individuals of European ancestry, which discovered 5,106 variants newly associated with 29 blood cell traits spanning immunity, oxygen transport, and clotting, and used fine-mapping to define 95% credible sets of likely causal variants. A complementary method, FINDOR (functionally informed novel discovery of risk loci), incorporated coding, conserved, regulatory, and linkage-disequilibrium-related genomic annotations into association analyses; applied to the full UK Biobank release (average N=416,000), it achieved a 13% average increase in genome-wide significant loci detected, with a replication slope of 0.66-0.69 in independent data, indicating reasonable consistency. Tissue expression data from GTEx (953 donors, false discovery rate below 0.05) shows this locus harbors an expression quantitative trait locus (eQTL), meaning genotype at this position correlates with nearby gene expression levels, with the alternate allele linked to increased CCDC88C expression in brain and liver and reduced expression of ENSG00000300783 in brain tissue GTEx Portal.

Reported associations

  • Blood cell traits: This locus was identified in a GWAS covering 563,085 European ancestry participants for 29 blood cell phenotypes spanning immunity, oxygen transport, and clotting; the specific phenotype(s) assigned to rs11627901 are not detailed in the available study materials
  • CCDC88C expression, cortical brain regions (eQTL): The alternate allele is associated with increased expression in brain cortex (slope +0.33, p=3.2e-12), frontal cortex (slope +0.32, p=2.5e-11), and anterior cingulate cortex (slope +0.28, p=1.6e-7) GTEx Portal
  • CCDC88C expression, peripheral tissues (eQTL): Increased expression also observed in liver (slope +0.30, p=2.1e-6), cultured fibroblasts (slope +0.21, p=1.6e-6), and sigmoid colon (slope +0.16, p=2.2e-6) GTEx Portal
  • ENSG00000300783 expression, brain (eQTL): The alternate allele is associated with reduced expression in cerebellar hemisphere (slope -0.42, p=8.5e-8) and anterior cingulate cortex (slope -0.31, p=8.0e-6) GTEx Portal

Evidence quality The blood cell GWAS spanned 563,085 European ancestry participants across UK Biobank and international cohorts, used fine-mapping to define 95% credible sets for each associated signal, and included replication in independent UK Biobank and non-UK Biobank datasets. The FINDOR analysis (average N=416,000, full UK Biobank release) demonstrated a statistically significant replication slope of 0.66-0.69 for the additional loci detected through functional enrichment, indicating the method does not inflate false positives. GTEx eQTL evidence is based on 953 donors at a false discovery rate below 0.05, with CCDC88C cortical brain associations reaching p-values below 1e-10, constituting strong statistical evidence for these molecular-level expression effects. Study materials do not provide variant-specific p-values or effect sizes for the blood cell trait associations at this locus, which is a key limitation for quantitative interpretation. All GWAS evidence derives from European ancestry populations, restricting generalizability to non-European groups.

Tissue-specific expression effects

  • CCDC88C: The alternate allele is linked to increased expression across brain cortex, frontal cortex, anterior cingulate cortex, liver, cultured fibroblasts, and sigmoid colon; effects are strongest in cortical brain tissue, where associations reach p-values below 1e-10 GTEx Portal
  • ENSG00000300783: The alternate allele is linked to reduced expression in cerebellar hemisphere and anterior cingulate cortex; this gene is identified by its Ensembl identifier and does not have a commonly assigned gene symbol in the available data GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs11627901?

rs11627901 is a genetic variant located in the PPP4R3A - CATSPERB locus. It was identified as one of thousands of variants associated with blood cell traits in a study of over 563,000 people of European ancestry.

Which blood cell traits is rs11627901 linked to?

This variant was identified in a study of 29 blood cell phenotypes covering traits related to immunity, oxygen transport, and blood clotting. The specific trait or traits assigned to this variant are not detailed in the available study materials.

What is the connection between rs11627901 and CCDC88C?

Tissue expression data from GTEx, covering 953 donors, shows that carriers of the alternate allele tend to have increased CCDC88C gene activity in several brain regions and in the liver. These are molecular-level observations and do not directly indicate clinical outcomes.

How reliable is the evidence for this variant?

The blood cell GWAS included 563,085 participants with fine-mapping and independent replication. GTEx eQTL data covers 953 donors at strict statistical thresholds, with cortical brain associations reaching p-values below 1e-10. However, variant-specific blood cell trait effect sizes are not available in the study materials, which is a key limitation.

Does rs11627901 affect brain function?

Tissue expression data shows this variant affects CCDC88C activity and that of a nearby gene in brain regions. These are gene expression observations at the molecular level. No studies in the available materials directly link this variant to brain function or neurological conditions.