Poster De Conférence Année : 2025

Comprehensive Identification of Pleiotropic Associations for Chronic Lymphocytic Leukemia

Résumé

Background. Chronic Lymphocytic Leukemia (CLL) is the most frequent type of leukemia in the western hemisphere [1]. Despite being an indolent B-cell disorder, it presents a wide array of possible clinical outcomes and can evolve aggressively [1]. Previous genome-wide association studies (GWAS) identified several rare and common genetic variants inherited at birth and predisposing to the development of CLL in later years [2]. Here we catalogue single nucleotide polymorphisms (SNPs) associated with CLL, which we map and extend by linkage disequilibrium across multiple genomic regions, and explore their pleiotropic potential, i.e. their involvement in other phenotypic traits and diseases. Results. Starting from the NHGRI-EBI Catalog of human GWAS, we selected 15 CLL studies with a minimum sample size > 1,000 individuals and further included 78 distinct SNPs reaching genome-wide significance (p < 5.10-8). This CLL lead SNP (lSNP) list was augmented with 736 proxy SNPs (pSNP) in high linkage disequilibrium (LD) with any lSNP (r2 > 0.9). We also identified and delimited 45 CLL genetic blocks using all the non-independent SNPs (r2 ≥ 0.1) from each CLL lSNP. Each block was assigned one of more ethnicities (from African, American, East Asian, European and South Asian ancestries), according to the discovery cohort of the respective lSNPs. Cohorts were labelled with multiple ethnicities for each ethnic group > 10% individuals. Subsequently, we identified all other genome-wide significant associations between human traits and lSNPs + pSNPs with matching ethnicities. This highlighted 784 pleiotropic phenotypes with CLL, which were summarized into 19 cross-trait categories, including other B-cell cancers of lymphoid and myeloid origin (n=190), solid cancers (n=48), auto-immune diseases (n=50), inflammatory diseases (n=52), diabetes (n=30), lipids (n=59), addictions (n=6), age-related (n=43), dermatology-related (n=6), obesity-related (n=10), cardiovascular (n=14) and cerebral function (n=5) traits. Conclusion. By revisiting the accumulated knowledge obtained through GWAS and reconstructing the pleiotropic associations around CLL genetic architecture, we confirm results that have already been noted in observational studies and validate genetically those that have been described at a physiological level. We also report new associations, notably with other hematologic malignancies and more aggressive lymphomas, widening the insight surrounding CLL development and evolution.

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hal-05219704 , version 1 (22-08-2025)

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  • HAL Id : hal-05219704 , version 1

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Anthony Haidamous, Vivian Zingui, Océane Reichert, David Meyre, Sébastien Hergalant. Comprehensive Identification of Pleiotropic Associations for Chronic Lymphocytic Leukemia. Journées Ouvertes en Biologie, Informatique et Mathématiques, Jul 2025, Bordeaux, France. JOBIM proceedings posters, pp.161, 2025. ⟨hal-05219704⟩
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