Polygenic risk score and risk of monoclonal B-cell lymphocytosis in caucasians and risk of chronic lymphocytic leukemia (CLL) in African Americans

Geffen Kleinstern; J. Brice Weinberg; Sameer A. Parikh; Esteban Braggio; Sara J. Achenbach; Dennis P. Robinson; Aaron D. Norman; Kari G. Rabe; Nicholas J. Boddicker; Celine M. Vachon; Connie E. Lesnick; Timothy G. Call; Danielle M. Brander; Laura Z. Rassenti; Thomas J. Kipps; Janet E. Olson; James R. Cerhan; Neil E. Kay; Richard R. Furman; Curtis A. Hanson; Tait D. Shanafelt; Susan L. Slager

doi:10.1038/s41375-021-01344-9

Polygenic risk score and risk of monoclonal B-cell lymphocytosis in caucasians and risk of chronic lymphocytic leukemia (CLL) in African Americans

Geffen Kleinstern, J. Brice Weinberg, Sameer A. Parikh, Esteban Braggio, Sara J. Achenbach, Dennis P. Robinson, Aaron D. Norman, Kari G. Rabe, Nicholas J. Boddicker, Celine M. Vachon, Connie E. Lesnick, Timothy G. Call, Danielle M. Brander, Laura Z. Rassenti, Thomas J. Kipps, Janet E. Olson, James R. Cerhan, Neil E. Kay, Richard R. Furman, Curtis A. HansonTait D. Shanafelt, Susan L. Slager

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	119-125
Number of pages	7
Journal	Leukemia
Volume	36
Issue number	1
DOIs	https://doi.org/10.1038/s41375-021-01344-9
State	Published - Jan 2022

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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Kleinstern, G., Weinberg, J. B., Parikh, S. A., Braggio, E., Achenbach, S. J., Robinson, D. P., Norman, A. D., Rabe, K. G., Boddicker, N. J., Vachon, C. M., Lesnick, C. E., Call, T. G., Brander, D. M., Rassenti, L. Z., Kipps, T. J., Olson, J. E., Cerhan, J. R., Kay, N. E., Furman, R. R., ... Slager, S. L. (2022). Polygenic risk score and risk of monoclonal B-cell lymphocytosis in caucasians and risk of chronic lymphocytic leukemia (CLL) in African Americans. Leukemia, 36(1), 119-125. https://doi.org/10.1038/s41375-021-01344-9

Kleinstern, G, Weinberg, JB, Parikh, SA , Braggio, E, Achenbach, SJ, Robinson, DP, Norman, AD, Rabe, KG, Boddicker, NJ, Vachon, CM, Lesnick, CE, Call, TG, Brander, DM, Rassenti, LZ, Kipps, TJ, Olson, JE , Cerhan, JR , Kay, NE, Furman, RR, Hanson, CA, Shanafelt, TD & Slager, SL 2022, 'Polygenic risk score and risk of monoclonal B-cell lymphocytosis in caucasians and risk of chronic lymphocytic leukemia (CLL) in African Americans', Leukemia, vol. 36, no. 1, pp. 119-125. https://doi.org/10.1038/s41375-021-01344-9

@article{3102debb1fc34faca5af56498d08fca7,

title = "Polygenic risk score and risk of monoclonal B-cell lymphocytosis in caucasians and risk of chronic lymphocytic leukemia (CLL) in African Americans",

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.",

author = "Geffen Kleinstern and Weinberg, {J. Brice} and Parikh, {Sameer A.} and Esteban Braggio and Achenbach, {Sara J.} and Robinson, {Dennis P.} and Norman, {Aaron D.} and Rabe, {Kari G.} and Boddicker, {Nicholas J.} and Vachon, {Celine M.} and Lesnick, {Connie E.} and Call, {Timothy G.} and Brander, {Danielle M.} and Rassenti, {Laura Z.} and Kipps, {Thomas J.} and Olson, {Janet E.} and Cerhan, {James R.} and Kay, {Neil E.} and Furman, {Richard R.} and Hanson, {Curtis A.} and Shanafelt, {Tait D.} and Slager, {Susan L.}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2022",

month = jan,

doi = "10.1038/s41375-021-01344-9",

language = "English (US)",

volume = "36",

pages = "119--125",

journal = "Leukemia",

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T1 - Polygenic risk score and risk of monoclonal B-cell lymphocytosis in caucasians and risk of chronic lymphocytic leukemia (CLL) in African Americans

AU - Kleinstern, Geffen

AU - Weinberg, J. Brice

AU - Parikh, Sameer A.

AU - Braggio, Esteban

AU - Achenbach, Sara J.

AU - Robinson, Dennis P.

AU - Norman, Aaron D.

AU - Rabe, Kari G.

AU - Boddicker, Nicholas J.

AU - Vachon, Celine M.

AU - Lesnick, Connie E.

AU - Call, Timothy G.

AU - Brander, Danielle M.

AU - Rassenti, Laura Z.

AU - Kipps, Thomas J.

AU - Olson, Janet E.

AU - Cerhan, James R.

AU - Kay, Neil E.

AU - Furman, Richard R.

AU - Hanson, Curtis A.

AU - Shanafelt, Tait D.

AU - Slager, Susan L.

PY - 2022/1

Y1 - 2022/1

N2 - 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.

AB - 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.

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Polygenic risk score and risk of monoclonal B-cell lymphocytosis in caucasians and risk of chronic lymphocytic leukemia (CLL) in African Americans

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