{"doi":"10.1038/s41375-021-01344-9","title":"Polygenic risk score and risk of monoclonal B-cell lymphocytosis in caucasians and risk of chronic lymphocytic leukemia (CLL) in African Americans","abstract":"Abstract Monoclonal B-cell lymphocytosis (MBL) is a precursor to CLL. Other than age, sex, and CLL family-history, little is known about factors associated with MBL risk. A polygenic-risk-score (PRS) of 41 CLL-susceptibility variants has been found to be associated with CLL risk among individuals of European-ancestry(EA). Here, we evaluate these variants, the PRS, and environmental factors for MBL risk. We also evaluate these variants and the CLL-PRS among African-American (AA) and EA-CLL cases and controls. Our study included 560 EA MBLs, 869 CLLs (696 EA/173 AA), and 2866 controls (2631 EA/235 AA). We used logistic regression, adjusting for age and sex, to estimate odds ratios (OR) and 95% confidence intervals within each race. We found significant associations with MBL risk among 21 of 41 variants and with the CLL-PRS (OR = 1.86, P = 1.9 × 10 −29 , c-statistic = 0.72). Little evidence of any association between MBL risk and environmental factors was observed. We observed significant associations of the CLL-PRS with EA-CLL risk (OR = 2.53, P = 4.0 × 10 −63 , c-statistic = 0.77) and AA-CLL risk (OR = 1.76, P = 5.1 × 10 −5 , c-statistic = 0.62). Inherited genetic factors and not environmental are associated with MBL risk. In particular, the CLL-PRS is a strong predictor for both risk of MBL and EA-CLL, but less so for AA-CLL supporting the need for further work in this population.","journal":"Leukemia","year":2021,"id":175605,"datarank":0.7255024630265021,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"self_citation_contribution":0.47032413238937254,"citation_network_contribution":0.25517833063712964,"self_endowment_contribution":0.47032413238937254,"citer_contribution":0.25517833063712964,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":12,"citers_with_citation_signal":9,"citers_with_endowment":9,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":339096,"name":"J. Brice Weinberg","orcid":"0000-0003-4052-5576","position":1,"is_corresponding":false},{"id":437794,"name":"Sameer A. Parikh","orcid":"0000-0002-3221-7314","position":2,"is_corresponding":false},{"id":451445,"name":"Esteban Braggio","orcid":"0000-0003-3860-4830","position":3,"is_corresponding":false},{"id":300279,"name":"Sara J. Achenbach","orcid":null,"position":4,"is_corresponding":false},{"id":503086,"name":"Dennis P. Robinson","orcid":"0009-0000-4812-9397","position":5,"is_corresponding":false},{"id":304439,"name":"Aaron D. Norman","orcid":"0000-0002-4208-2708","position":6,"is_corresponding":false},{"id":420931,"name":"Kari G. Rabe","orcid":"0000-0002-7313-1875","position":7,"is_corresponding":false},{"id":274802,"name":"Nicholas Boddicker","orcid":"0000-0002-6784-2072","position":8,"is_corresponding":false},{"id":328451,"name":"Celine M. Vachon","orcid":"0000-0002-1962-9322","position":9,"is_corresponding":false},{"id":490131,"name":"Connie Lesnick","orcid":"0009-0008-2812-1214","position":10,"is_corresponding":false},{"id":454796,"name":"Timothy G. Call","orcid":"0000-0002-8465-9587","position":11,"is_corresponding":false},{"id":233562,"name":"Danielle M. Brander","orcid":"0000-0002-9581-2807","position":12,"is_corresponding":false},{"id":352373,"name":"Laura Z. Rassenti","orcid":null,"position":13,"is_corresponding":false},{"id":242767,"name":"Thomas J. Kipps","orcid":"0000-0002-0064-4549","position":14,"is_corresponding":false},{"id":70827,"name":"Janet E. Olson","orcid":"0000-0003-4944-7789","position":15,"is_corresponding":false},{"id":302818,"name":"James R. Cerhan","orcid":"0000-0002-7482-178X","position":16,"is_corresponding":false},{"id":451444,"name":"Neil E. Kay","orcid":"0000-0002-5951-5055","position":17,"is_corresponding":false},{"id":233553,"name":"Richard R. Furman","orcid":"0000-0003-1677-7626","position":18,"is_corresponding":false},{"id":475101,"name":"Curtis A. Hanson","orcid":"0000-0003-1333-5355","position":19,"is_corresponding":false},{"id":285630,"name":"Tait D. Shanafelt","orcid":"0000-0002-7106-5202","position":20,"is_corresponding":false},{"id":264807,"name":"Susan L. Slager","orcid":"0000-0002-5173-4712","position":21,"is_corresponding":false},{"id":404947,"name":"Geffen Kleinstern","orcid":"0000-0001-6148-0421","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:47:15.431199Z","pmid":"34285341","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}