Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression? Cabrera Serrano, Antonio José Sáinz Pérez, Juan Chronic lymphocytic leukemia Overall survival Genetic variants Susceptibility Polygenic risk scoring Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults worldwide. Although genome-wide association studies (GWAS) have uncovered the germline genetic component underlying CLL susceptibility, the potential use of GWAS-identified risk variants to predict disease progression and patient survival remains unexplored. Here, we evaluated whether 41 GWAS-identified risk variants for CLL could influence overall survival (OS) and disease progression, defined as time to first treatment (TTFT) in a cohort of 1039 CLL cases ascertained through the CRuCIAL consortium. Although this is the largest study assessing the effect of GWAS-identified susceptibility variants for CLL on OS, we only found a weak association of ten single nucleotide polymorphisms (SNPs) with OS (p < 0.05) that did not remain significant after correction for multiple testing. In line with these results, polygenic risk scores (PRSs) built with these SNPs in the CRuCIAL cohort showed a modest association with OS and a low capacity to predict patient survival, with an area under the receiver operating characteristic curve (AUROC) of 0.57. Similarly, seven SNPs were associated with TTFT (p < 0.05); however, these did not reach the multiple testing significance threshold, and the meta-analysis with previous published data did not confirm any of the associations. As expected, PRSs built with these SNPs showed reduced accuracy in prediction of disease progression (AUROC = 0.62). These results suggest that susceptibility variants for CLL do not impact overall survival and disease progression in CLL patients 2023-06-22T08:49:23Z 2023-06-22T08:49:23Z 2023-04-28 journal article Cabrera-Serrano, A.J.; Sánchez-Maldonado, J.M.; ter Horst, R.; Macauda, A.; García-Martín, P.; Benavente, Y.; Landi, S.; Clay-Gilmour, A.; Niazi, Y.; Espinet, B.; et al. Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression? Int. J. Mol. Sci. 2023, 24, 8005. https://doi.org/10.3390/ijms24098005 https://hdl.handle.net/10481/82716 10.3390/ijms24098005 eng info:eu-repo/grantAgreement/EC/Horizon 2020/856620 http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional MDPI