rs10965258 (CDKN2B-AS1): Genetic Locus Variant

Key takeaways

• rs10965258 is located in the CDKN2B-AS1 gene region, a locus examined across thousands of complex traits in large genetic studies
• Studies including diverse ancestry groups have found thousands of associations that would be missed using only European-ancestry samples
• Blood cell traits and the biology of blood cell production (hematopoiesis) are among the phenotype categories studied alongside this genomic region
• Large sample sizes, exceeding 600,000 participants in some studies, support more reliable fine-mapping of causal variants at this locus

What the research says rs10965258 sits within the CDKN2B-AS1 gene region and has been examined as part of large-scale, multi-population genome-wide association studies (GWAS - studies that scan the entire genome for variants statistically linked to traits or diseases). One study enrolled 635,969 participants from four genetic ancestry groups and identified 26,049 variant-trait associations across 1,270 traits, with 3,477 of those associations only detectable by including non-European participants. A second study of 563,085 European ancestry participants conducted one of the largest GWAS of blood cell phenotypes to date, identifying 5,106 new genetic variants associated with 29 blood cell traits.

Reported associations

• Complex traits across diverse populations: The Million Veteran Program study covered 2,068 traits in up to 635,969 participants from African, Admixed American, East Asian, and European ancestry groups, applying fine-mapping (a statistical method for narrowing down which specific variant within a region is most likely causal) to prioritize putative causal variants; 3,477 associations were only significant once non-European participants were included
• Blood cell phenotypes: A study of 29 blood cell traits in 563,085 participants identified 5,106 new genetic variants and used epigenomic and transcriptomic profiling of hematopoietic cells (cells that give rise to blood cells) to assess the functional relevance of associated loci across a wide allelic spectrum

Evidence quality The two contributing studies are large-scale and well-powered. The Million Veteran Program study identified 57,601 independent fine-mapped signals across 936 traits, with 15,045 signals mapped to a single variant with high confidence. The blood cell study integrated data from the UK Biobank with a large international collaborative dataset and found results consistent with the omnigenic model (the hypothesis that essentially all expressed genes in a relevant tissue can influence a complex trait, each contributing a small effect). Both studies applied genome-wide significance thresholds and replicated findings across independent cohorts. A key strength of the MVP study is its diverse ancestry composition; 3,477 unique associations were only discoverable once non-European participants were included, highlighting that population diversity is critical for a complete picture of variant associations at loci like CDKN2B-AS1. The specific p-values and per-allele effect sizes for rs10965258 individually are not reported in the provided excerpts of these studies.

Lifestyle considerations No lifestyle considerations on file for this variant.