Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis
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Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis. / Kleinstern, Geffen; Camp, Nicola J.; Goldin, Lynn R.; Vachon, Celine M.; Vajdic, Claire M.; De Sanjose, Silvia; Weinberg, J. Brice; Benavente, Yolanda; Casabonne, Delphine; Liebow, Mark; Nieters, Alexandra; Hjalgrim, Henrik; Melbye, Mads; Glimelius, Bengt; Adami, Hans Olov; Boffetta, Paolo; Brennan, Paul; Maynadie, Marc; McKay, James; Cocco, Pier Luigi; Shanafelt, Tait D.; Call, Timothy G.; Norman, Aaron D.; Hanson, Curtis; Robinson, Dennis; Chaffee, Kari G.; Brooks-Wilson, Angela R.; Monnereau, Alain; Clavel, Jacqueline; Glenn, Martha; Curtin, Karen; Conde, Lucia; Bracci, Paige M.; Morton, Lindsay M.; Cozen, Wendy; Severson, Richard K.; Chanock, Stephen J.; Spinelli, John J.; Johnston, James B.; Rothman, Nathaniel; Skibola, Christine F.; Leis, Jose F.; Kay, Neil E.; Smedby, Karin E.; Berndt, Sonja I.; Cerhan, James R.; Caporaso, Neil; Slager, Susan L.
I: Blood, Bind 131, Nr. 23, 2018, s. 2541-2551.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis
AU - Kleinstern, Geffen
AU - Camp, Nicola J.
AU - Goldin, Lynn R.
AU - Vachon, Celine M.
AU - Vajdic, Claire M.
AU - De Sanjose, Silvia
AU - Weinberg, J. Brice
AU - Benavente, Yolanda
AU - Casabonne, Delphine
AU - Liebow, Mark
AU - Nieters, Alexandra
AU - Hjalgrim, Henrik
AU - Melbye, Mads
AU - Glimelius, Bengt
AU - Adami, Hans Olov
AU - Boffetta, Paolo
AU - Brennan, Paul
AU - Maynadie, Marc
AU - McKay, James
AU - Cocco, Pier Luigi
AU - Shanafelt, Tait D.
AU - Call, Timothy G.
AU - Norman, Aaron D.
AU - Hanson, Curtis
AU - Robinson, Dennis
AU - Chaffee, Kari G.
AU - Brooks-Wilson, Angela R.
AU - Monnereau, Alain
AU - Clavel, Jacqueline
AU - Glenn, Martha
AU - Curtin, Karen
AU - Conde, Lucia
AU - Bracci, Paige M.
AU - Morton, Lindsay M.
AU - Cozen, Wendy
AU - Severson, Richard K.
AU - Chanock, Stephen J.
AU - Spinelli, John J.
AU - Johnston, James B.
AU - Rothman, Nathaniel
AU - Skibola, Christine F.
AU - Leis, Jose F.
AU - Kay, Neil E.
AU - Smedby, Karin E.
AU - Berndt, Sonja I.
AU - Cerhan, James R.
AU - Caporaso, Neil
AU - Slager, Susan L.
PY - 2018
Y1 - 2018
N2 - Inherited loci have been found to be associated with risk of chronic lymphocytic leukemia (CLL). A combined polygenic risk score (PRS) of representative single nucleotide polymorphisms (SNPs) from these loci may improve risk prediction over individual SNPs. Herein, we evaluated the association of a PRS with CLL risk and its precursor, monoclonal B-cell lymphocytosis (MBL). We assessed its validity and discriminative ability in an independent sample and evaluated effect modification and confounding by family history (FH) of hematological cancers. For discovery, we pooled genotype data on 41 representative SNPs from 1499 CLL and 2459 controls from the InterLymph Consortium. For validation, we used data from 1267 controls from Mayo Clinic and 201 CLL, 95 MBL, and 144 controls with a FH of CLL from the Genetic Epidemiology of CLL Consortium. We used odds ratios (ORs) to estimate disease associations with PRS and c-statistics to assess discriminatory accuracy. In InterLymph, the continuous PRS was strongly associated with CLL risk (OR, 2.49; P 5 4.4310294). We replicated these findings in the Genetic Epidemiology of CLL Consortium and Mayo controls (OR, 3.02; P 5 7.8 3 10230) and observed high discrimination (c-statistic 5 0.78). When jointly modeled with FH, PRS retained its significance, along with FH status. Finally, we found a highly significant association of the continuous PRS with MBL risk (OR, 2.81; P 5 9.8 310216). In conclusion, our validated PRS was strongly associated with CLL risk, adding information beyond FH.The PRS provides a means of identifying those individuals at greater risk for CLL as well as those at increased risk of MBL, a condition that has potential clinical impact beyond CLL. (Blood. 2018;131(23):2541-2551).
AB - Inherited loci have been found to be associated with risk of chronic lymphocytic leukemia (CLL). A combined polygenic risk score (PRS) of representative single nucleotide polymorphisms (SNPs) from these loci may improve risk prediction over individual SNPs. Herein, we evaluated the association of a PRS with CLL risk and its precursor, monoclonal B-cell lymphocytosis (MBL). We assessed its validity and discriminative ability in an independent sample and evaluated effect modification and confounding by family history (FH) of hematological cancers. For discovery, we pooled genotype data on 41 representative SNPs from 1499 CLL and 2459 controls from the InterLymph Consortium. For validation, we used data from 1267 controls from Mayo Clinic and 201 CLL, 95 MBL, and 144 controls with a FH of CLL from the Genetic Epidemiology of CLL Consortium. We used odds ratios (ORs) to estimate disease associations with PRS and c-statistics to assess discriminatory accuracy. In InterLymph, the continuous PRS was strongly associated with CLL risk (OR, 2.49; P 5 4.4310294). We replicated these findings in the Genetic Epidemiology of CLL Consortium and Mayo controls (OR, 3.02; P 5 7.8 3 10230) and observed high discrimination (c-statistic 5 0.78). When jointly modeled with FH, PRS retained its significance, along with FH status. Finally, we found a highly significant association of the continuous PRS with MBL risk (OR, 2.81; P 5 9.8 310216). In conclusion, our validated PRS was strongly associated with CLL risk, adding information beyond FH.The PRS provides a means of identifying those individuals at greater risk for CLL as well as those at increased risk of MBL, a condition that has potential clinical impact beyond CLL. (Blood. 2018;131(23):2541-2551).
U2 - 10.1182/blood-2017-11-814608
DO - 10.1182/blood-2017-11-814608
M3 - Journal article
C2 - 29674426
AN - SCOPUS:85048273566
VL - 131
SP - 2541
EP - 2551
JO - Blood
JF - Blood
SN - 0006-4971
IS - 23
ER -
ID: 257834651