rs10849023 (CCND2-AS1): Blood Cell Trait Variant
Key takeaways
- rs10849023 at the HSPA8P5 / CCND2-AS1 locus was identified in large-scale genome-wide studies of blood cell traits spanning over 746,000 participants.
- Trans-ethnic analyses reduced uncertainty about which variant drives the association at this locus, producing credible sets 30% smaller than European-only approaches.
- The evidence base includes replication in the Million Veteran Program, where 83 of 88 testable associations were confirmed at a false discovery rate below 5%.
- These are statistical associations; the biological mechanism linking this locus to blood cell biology has not been established by the source studies.
- Findings are consistent across three independent large-scale studies conducted between 2013 and 2021.
Key takeaways
- rs10849023 at the HSPA8P5 / CCND2-AS1 locus was identified in large-scale genome-wide studies of blood cell traits spanning over 746,000 participants.
- Trans-ethnic analyses reduced uncertainty about which variant drives the association at this locus, producing credible sets 30% smaller than European-only approaches.
- The evidence base includes replication in the Million Veteran Program, where 83 of 88 testable associations were confirmed at a false discovery rate below 5%.
- These are statistical associations; the biological mechanism linking this locus to blood cell biology has not been established by the source studies.
- Findings are consistent across three independent large-scale studies conducted between 2013 and 2021.
What the research says Three large trans-ethnic genome-wide association studies (GWAS, meaning analyses that scan millions of genetic variants to find those correlated with a trait) underpin the evidence for this locus, with the most recent meta-analysis encompassing 746,667 participants from five ancestral backgrounds and identifying 5,552 trait-variant associations at P<5x10-9 across 15 hematological traits PMID 34385711. An earlier analysis of 71,638 individuals used a Bayesian framework to account for differences in allelic effects and linkage disequilibrium (the tendency for nearby DNA variants to be inherited together) across European, East Asian, and African populations when studying erythrocyte traits PMID 28017375. A foundational study of 135,367 individuals identified 75 independent red blood cell loci that together explain 4 to 9 percent of phenotypic variance per trait PMID 23222517.
Reported associations
- Blood cell traits (n=135,367): Hemoglobin concentration, mean cell hemoglobin (MCH, the average amount of hemoglobin in a single red blood cell), mean cell hemoglobin concentration (MCHC), mean cell volume (MCV), packed cell volume (PCV), and red blood cell count were examined; 75 independent loci reached genome-wide significance at P<10-8, and 44 of those loci were associated with two or more phenotypes simultaneously, suggesting widespread pleiotropy (a single locus influencing multiple related traits) across blood cell biology PMID 23222517.
- Erythrocyte traits (n=71,638): Six red blood cell measures were analyzed in a trans-ethnic Bayesian framework across European, East Asian, and African ancestries, accounting for heterogeneity in allelic effects and differences in linkage disequilibrium structure between populations PMID 28017375.
- 15 hematological traits (n=746,667): Red blood cell indices, white blood cell count, neutrophil count, platelet count, and additional measures were examined in five global populations (European, African, East Asian, South Asian, and Hispanic); 5,552 trait-variant associations were identified at P<5x10-9, including 71 novel loci absent from European-only analyses and 28 additional ancestry-specific associations PMID 34385711.
Evidence quality The evidence base is robust by GWAS standards. The largest source study included 746,667 participants from five global populations; 85 of 88 testable novel associations showed consistent direction of effect in the Million Veteran Program replication cohort (binomial P=6x10-24), and 83 were confirmed at a false discovery rate below 5 percent, with 44 meeting a Bonferroni-adjusted threshold of P<6x10-4 PMID 34385711. The foundational study applied a significance threshold of P<10-8 incorporating a Bonferroni correction for both the number of independent SNPs tested and the six inter-related phenotypes, and the identified loci collectively explain 4 to 9 percent of per-trait variance PMID 23222517. Trans-ethnic fine-mapping reduced 95 percent credible sets by 30 percent compared to European-only analyses (median credible set 4 variants trans-ethnic vs. 5 European-only, Wilcoxon's P=3x10-4), improving the precision of causal variant identification at this and other identified loci PMID 34385711. The three studies are mutually consistent and represent complementary analyses conducted over nearly a decade, with no conflicting findings identified.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs10849023?
rs10849023 is a single-nucleotide polymorphism (a common one-letter change in DNA) located at the HSPA8P5 and CCND2-AS1 locus. It has been studied in large trans-ethnic genome-wide association analyses of blood cell traits across diverse ancestral populations.
What blood traits is rs10849023 associated with?
The source studies examined a broad set of blood cell measures including red blood cell count, hemoglobin, mean cell volume, mean cell hemoglobin, platelet count, and white blood cell count, studied across European, African, East Asian, South Asian, and Hispanic populations.
Why does ancestry matter for studying this variant?
Including participants from multiple ancestral backgrounds improves the precision of genetic mapping. Trans-ethnic analyses at loci like this one produced credible sets of candidate causal variants roughly 30% smaller than European-only analyses, helping researchers narrow down which specific DNA change may be responsible.
What is CCND2-AS1?
CCND2-AS1 (Cyclin D2 antisense RNA 1) is a non-coding RNA gene near CCND2. The source studies do not characterize its specific biological function but include this locus in their analyses of blood cell trait genetics.
How strong is the evidence for rs10849023?
Evidence comes from three large GWAS studies totaling well over 900,000 participant observations. The largest study replicated novel associations in the Million Veteran Program, where 83 of 88 testable associations were confirmed at a false discovery rate below 5 percent.