{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:41:19Z","timestamp":1787002879647,"version":"build-2736575974"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    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\u2009=\u20091.86,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20091.9\u2009\u00d7\u200910\n                    <jats:sup>\u221229<\/jats:sup>\n                    , c-statistic\u2009=\u20090.72). 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\u2009=\u20092.53,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20094.0\u2009\u00d7\u200910\n                    <jats:sup>\u221263<\/jats:sup>\n                    , c-statistic\u2009=\u20090.77) and AA-CLL risk (OR\u2009=\u20091.76,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20095.1\u2009\u00d7\u200910\n                    <jats:sup>\u22125<\/jats:sup>\n                    , c-statistic\u2009=\u20090.62). 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.\n                  <\/jats:p>","DOI":"10.1038\/s41375-021-01344-9","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T02:02:56Z","timestamp":1626746576000},"page":"119-125","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Polygenic risk score and risk of monoclonal B-cell lymphocytosis in caucasians and risk of chronic lymphocytic leukemia (CLL) in African Americans"],"prefix":"10.1038","volume":"36","author":[{"given":"Geffen","family":"Kleinstern","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Brice","family":"Weinberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3221-7314","authenticated-orcid":false,"given":"Sameer A.","family":"Parikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"Braggio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara J.","family":"Achenbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis P.","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron D.","family":"Norman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari G.","family":"Rabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Boddicker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1962-9322","authenticated-orcid":false,"given":"Celine M.","family":"Vachon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie E.","family":"Lesnick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy G.","family":"Call","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle M.","family":"Brander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Z.","family":"Rassenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0064-4549","authenticated-orcid":false,"given":"Thomas J.","family":"Kipps","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4944-7789","authenticated-orcid":false,"given":"Janet E.","family":"Olson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7482-178X","authenticated-orcid":false,"given":"James R.","family":"Cerhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5951-5055","authenticated-orcid":false,"given":"Neil E.","family":"Kay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard R.","family":"Furman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis A.","family":"Hanson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tait D.","family":"Shanafelt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5173-4712","authenticated-orcid":false,"given":"Susan L.","family":"Slager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"key":"1344_CR1","doi-asserted-by":"publisher","first-page":"5446","DOI":"10.1182\/blood-2007-06-093906","volume":"111","author":"M Hallek","year":"2008","unstructured":"Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111:5446\u201356.","journal-title":"Blood"},{"key":"1344_CR2","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1093\/ajcp\/108.4.378","volume":"108","author":"EJ Moreau","year":"1997","unstructured":"Moreau EJ, Matutes E, A\u2019Hern RP, Morilla AM, Morilla RM, Owusu-Ankomah KA, et al. Improvement of the chronic lymphocytic leukemia scoring system with the monoclonal antibody SN8 (CD79b). Am J Clin Pathol. 1997;108:378\u201382.","journal-title":"Am J Clin Pathol"},{"key":"1344_CR3","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1136\/jcp.51.5.364","volume":"51","author":"L Ginaldi","year":"1998","unstructured":"Ginaldi L, De Martinis M, Matutes E, Farahat N, Morilla R, Catovsky D. 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N Engl J Med. 2009;360:659\u201367.","journal-title":"N Engl J Med"},{"key":"1344_CR6","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1182\/blood-2008-09-176933","volume":"114","author":"A Dagklis","year":"2009","unstructured":"Dagklis A, Fazi C, Sala C, Cantarelli V, Scielzo C, Massacane R, et al. The immunoglobulin gene repertoire of low-count chronic lymphocytic leukemia (CLL)-like monoclonal B lymphocytosis is different from CLL: diagnostic implications for clinical monitoring. Blood. 2009;114:26\u201332.","journal-title":"Blood"},{"key":"1344_CR7","doi-asserted-by":"publisher","first-page":"2337","DOI":"10.1182\/blood-2003-09-3277","volume":"103","author":"P Ghia","year":"2004","unstructured":"Ghia P, Prato G, Scielzo C, Stella S, Geuna M, Guida G, et al. Monoclonal CD5+ and CD5- B-lymphocyte expansions are frequent in the peripheral blood of the elderly. Blood. 2004;103:2337\u201342.","journal-title":"Blood"},{"key":"1344_CR8","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1182\/blood.V98.1.29","volume":"98","author":"AC Rawstron","year":"2001","unstructured":"Rawstron AC, Kennedy B, Evans PA, Davies FE, Richards SJ, Haynes AP, et al. Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy. Blood. 2001;98:29\u201335.","journal-title":"Blood"},{"key":"1344_CR9","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1111\/j.1365-2141.2010.08339.x","volume":"151","author":"LR Goldin","year":"2010","unstructured":"Goldin LR, Lanasa MC, Slager SL, Cerhan JR, Vachon CM, Strom SS, et al. Common occurrence of monoclonal B-cell lymphocytosis among members of high-risk CLL families. Br J Haematol. 2010;151:152\u20138.","journal-title":"Br J Haematol"},{"key":"1344_CR10","first-page":"1","volume":"52","author":"GE Marti","year":"2003","unstructured":"Marti GE, Carter P, Abbasi F, Washington GC, Jain N, Zenger VE, et al. B-cell monoclonal lymphocytosis and B-cell abnormalities in the setting of familial B-cell chronic lymphocytic leukemia. Cytom Part B Clin Cytom. 2003;52:1\u201312.","journal-title":"Cytom Part B Clin Cytom"},{"key":"1344_CR11","doi-asserted-by":"publisher","first-page":"S19","DOI":"10.1002\/cyto.b.20533","volume":"78","author":"AC Rawstron","year":"2010","unstructured":"Rawstron AC, Shanafelt T, Lanasa MC, Landgren O, Hanson C, Orfao A, et al. Different biology and clinical outcome according to the absolute numbers of clonal B-cells in monoclonal B-cell lymphocytosis (MBL). 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PloS one. 2012;7:e52808.","journal-title":"PloS one"},{"key":"1344_CR33","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1111\/j.1365-2141.2009.07861.x","volume":"147","author":"DM Matos","year":"2009","unstructured":"Matos DM, Ismael SJ, Scrideli CA, de Oliveira FM, Rego EM, Falc\u00e3o RP. Monoclonal B-cell lymphocytosis in first-degree relatives of patients with sporadic (non-familial) chronic lymphocytic leukaemia. Br J Haematol. 2009;147:339\u201346.","journal-title":"Br J Haematol"}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41375-021-01344-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-021-01344-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-021-01344-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T18:06:18Z","timestamp":1641319578000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41375-021-01344-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,20]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["1344"],"URL":"https:\/\/doi.org\/10.1038\/s41375-021-01344-9","relation":{},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,20]]},"assertion":[{"value":"9 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 July 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 July 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}