Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

Sonja I. Berndt; Christine F. Skibola; Vijai Joseph; Nicola J. Camp; Alexandra Nieters; Zhaoming Wang; Wendy Cozen; Alain Monnereau; Sophia S. Wang; Rachel S. Kelly; Qing Lan; Lauren R. Teras; Nilanjan Chatterjee; Charles C. Chung; Meredith Yeager; Angela R. Brooks-Wilson; Patricia Hartge; Mark P. Purdue; Brenda M. Birmann; Bruce K. Armstrong; Pierluigi Cocco; Yawei Zhang; Gianluca Severi; Anne Zeleniuch-Jacquotte; Charles Lawrence; Laurie Burdette; Jeffrey Yuenger; Amy Hutchinson; Kevin B. Jacobs; Timothy G. Call; Tait D. Shanafelt; Anne J. Novak; Neil E. Kay; Mark Liebow; Alice H. Wang; Karin E. Smedby; Hans Olov Adami; Mads Melbye; Bengt Glimelius; Ellen T. Chang; Martha Glenn; Karen Curtin; Lisa A. Cannon-Albright; Brandt Jones; W. Ryan Diver; Brian K. Link; George J. Weiner; Lucia Conde; Paige M. Bracci; Jacques Riby; Elizabeth A. Holly; Martyn T. Smith; Rebecca D. Jackson; Lesley F. Tinker; Yolanda Benavente; Nikolaus Becker; Paolo Boffetta; Paul Brennan; Lenka Foretova; Marc Maynadie; James McKay; Anthony Staines; Kari G. Rabe; Sara J. Achenbach; Celine M. Vachon; Lynn R. Goldin; Sara S. Strom; Mark C. Lanasa; Logan G. Spector; Jose F. Leis; Julie M. Cunningham; J. Brice Weinberg; Vicki A. Morrison; Neil E. Caporaso; Aaron D. Norman; Martha S. Linet; Anneclaire J. De Roos; Lindsay M. Morton; Richard K. Severson; Elio Riboli; Paolo Vineis; Rudolph Kaaks; Dimitrios Trichopoulos; Giovanna Masala; Elisabete Weiderpass; María Dolores Chirlaque; Roel C.H. Vermeulen; Ruth C. Travis; Graham G. Giles; Demetrius Albanes; Jarmo Virtamo; Stephanie Weinstein; Jacqueline Clavel; Tongzhang Zheng; Theodore R. Holford; Kenneth Offit; Andrew Zelenetz; Robert J. Klein; John J. Spinelli; Kimberly A. Bertrand; Francine Laden; Edward Giovannucci; Peter Kraft; Anne Kricker; Jenny Turner; Claire M. Vajdic; Maria Grazia Ennas; Giovanni M. Ferri; Lucia Miligi; Liming Liang; Joshua Sampson; Simon Crouch; Ju Hyun Park; Kari E. North; Angela Cox; John A. Snowden; Josh Wright; Angel Carracedo; Carlos Lopez-Otin; Silvia Bea; Itziar Salaverria; David Martin-Garcia; Elias Campo; Joseph F. Fraumeni; Silvia De Sanjose; Henrik Hjalgrim; James R. Cerhan; Stephen J. Chanock; Nathaniel Rothman; Susan L. Slager

doi:10.1038/ng.2652

Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

Sonja I. Berndt
, Christine F. Skibola
, Vijai Joseph
, Nicola J. Camp
, Alexandra Nieters
, Zhaoming Wang
, Wendy Cozen
, Alain Monnereau
, Sophia S. Wang
, Rachel S. Kelly
, Qing Lan
, Lauren R. Teras
, Nilanjan Chatterjee
, Charles C. Chung
, Meredith Yeager
, Angela R. Brooks-Wilson
, Patricia Hartge
, Mark P. Purdue
, Brenda M. Birmann
, Bruce K. Armstrong

Pierluigi Cocco, Yawei Zhang, Gianluca Severi, Anne Zeleniuch-Jacquotte, Charles Lawrence, Laurie Burdette, Jeffrey Yuenger, Amy Hutchinson, Kevin B. Jacobs, Timothy G. Call, Tait D. Shanafelt, Anne J. Novak, Neil E. Kay, Mark Liebow, Alice H. Wang, Karin E. Smedby, Hans Olov Adami, Mads Melbye, Bengt Glimelius, Ellen T. Chang, Martha Glenn, Karen Curtin, Lisa A. Cannon-Albright, Brandt Jones, W. Ryan Diver, Brian K. Link, George J. Weiner, Lucia Conde, Paige M. Bracci, Jacques Riby, Elizabeth A. Holly, Martyn T. Smith, Rebecca D. Jackson, Lesley F. Tinker, Yolanda Benavente, Nikolaus Becker, Paolo Boffetta, Paul Brennan, Lenka Foretova, Marc Maynadie, James McKay, Anthony Staines, Kari G. Rabe, Sara J. Achenbach, Celine M. Vachon, Lynn R. Goldin, Sara S. Strom, Mark C. Lanasa, Logan G. Spector, Jose F. Leis, Julie M. Cunningham, J. Brice Weinberg, Vicki A. Morrison, Neil E. Caporaso, Aaron D. Norman, Martha S. Linet, Anneclaire J. De Roos, Lindsay M. Morton, Richard K. Severson, Elio Riboli, Paolo Vineis, Rudolph Kaaks, Dimitrios Trichopoulos, Giovanna Masala, Elisabete Weiderpass, María Dolores Chirlaque, Roel C.H. Vermeulen, Ruth C. Travis, Graham G. Giles, Demetrius Albanes, Jarmo Virtamo, Stephanie Weinstein, Jacqueline Clavel, Tongzhang Zheng, Theodore R. Holford, Kenneth Offit, Andrew Zelenetz, Robert J. Klein, John J. Spinelli, Kimberly A. Bertrand, Francine Laden, Edward Giovannucci, Peter Kraft, Anne Kricker, Jenny Turner, Claire M. Vajdic, Maria Grazia Ennas, Giovanni M. Ferri, Lucia Miligi, Liming Liang, Joshua Sampson, Simon Crouch, Ju Hyun Park, Kari E. North, Angela Cox, John A. Snowden, Josh Wright, Angel Carracedo, Carlos Lopez-Otin, Silvia Bea, Itziar Salaverria, David Martin-Garcia, Elias Campo, Joseph F. Fraumeni, Silvia De Sanjose, Henrik Hjalgrim, James R. Cerhan, Stephen J. Chanock, Nathaniel Rothman, Susan L. Slager

Department of Statistics

National Institutes of Health
University of California at Berkeley
University of Alabama at Birmingham
Memorial Sloan-Kettering Cancer Center
University of Utah
University of Freiburg
University of Southern California
Institut national de la santé et de la recherche médicale
Centre Georges-François Leclerc
City of Hope National Med Center
Imperial College London
American Cancer Society
Provincial Health Services Authority
Simon Fraser University
Brigham and Women’s Hospital
The University of Sydney
University of Cagliari
Yale University
Cancer Council Victoria
New York University
Westat
Mayo Clinic Rochester, MN
Karolinska Institutet
Harvard University
Statens Serum Institut
Uppsala University
Exponent, Inc.
Stanford University
VA Medical Center
University of Iowa
University of California at San Francisco
Ohio State University
Fred Hutchinson Cancer Research Center
Institute Catala Oncologia
Centro de Investigacion Biomedica en Red CIBER Epidemiologia y Salud Publica
German Cancer Research Center
Icahn School of Medicine at Mount Sinai
International Agency for Research on Cancer
Masaryk Memorial Cancer Institute
Université de Bourgogne
Dublin City University
University of Texas MD Anderson Cancer Center
Duke University
University of Minnesota Twin Cities
Wayne State University
Human Genetics Foundation
Academy of Athens
Helenic Health Foundation
Centro Per Lo Studio E La Prevenzione Oncologica
University of Tromsø – The Arctic University of Norway
Cancer Registry of Norway Institute of Population-Based Cancer Research
Folkhalsan
Murcia Regional Health Authority
Utrecht University
University of Oxford
National Institute for Health and Welfare
Macquarie University
Sonic Healthcare
University of New South Wales
University of Bari
ISPO
University of York
University of North Carolina at Chapel Hill
University of Sheffield
Sheffield Teaching Hospitals NHS Foundation Trust
University of Santiago de Compostela
University of Oviedo
University of Barcelona

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

177 Scopus citations

Abstract

Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10^-14), 18q21.33 (BCL2, P = 7.76 × 10^-11), 11p15.5 (C11orf21, P = 2.15 × 10 ^-10), 4q25 (LEF1, P = 4.24 × 10^-10), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 × 10^-9), 9p21.3 (CDKN2B-AS1, P = 1.27 × 10^-8), 18q21.32 (PMAIP1, P = 2.51 × 10 ^-8), 15q15.1 (BMF, P = 2.71 × 10^-10) and 2p22.2 (QPCT, P = 1.68 × 10^-8), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 × 10^-18). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 × 10^-8) and 5p15.33 (TERT, P = 1.92 × 10^-7). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.

Original language	English
Pages (from-to)	868-876
Number of pages	9
Journal	Nature Genetics
Volume	45
Issue number	8
DOIs	https://doi.org/10.1038/ng.2652
State	Published - Aug 2013

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Berndt, S. I., Skibola, C. F., Joseph, V., Camp, N. J., Nieters, A., Wang, Z., Cozen, W., Monnereau, A., Wang, S. S., Kelly, R. S., Lan, Q., Teras, L. R., Chatterjee, N., Chung, C. C., Yeager, M., Brooks-Wilson, A. R., Hartge, P., Purdue, M. P., Birmann, B. M., ... Slager, S. L. (2013). Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia. Nature Genetics, 45(8), 868-876. https://doi.org/10.1038/ng.2652

@article{6b2c324bcfda474b99932cd64c65a611,

title = "Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia",

abstract = "Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10-14), 18q21.33 (BCL2, P = 7.76 × 10-11), 11p15.5 (C11orf21, P = 2.15 × 10 -10), 4q25 (LEF1, P = 4.24 × 10-10), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 × 10-9), 9p21.3 (CDKN2B-AS1, P = 1.27 × 10-8), 18q21.32 (PMAIP1, P = 2.51 × 10 -8), 15q15.1 (BMF, P = 2.71 × 10-10) and 2p22.2 (QPCT, P = 1.68 × 10-8), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 × 10-18). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 × 10-8) and 5p15.33 (TERT, P = 1.92 × 10-7). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.",

author = "Berndt, \{Sonja I.\} and Skibola, \{Christine F.\} and Vijai Joseph and Camp, \{Nicola J.\} and Alexandra Nieters and Zhaoming Wang and Wendy Cozen and Alain Monnereau and Wang, \{Sophia S.\} and Kelly, \{Rachel S.\} and Qing Lan and Teras, \{Lauren R.\} and Nilanjan Chatterjee and Chung, \{Charles C.\} and Meredith Yeager and Brooks-Wilson, \{Angela R.\} and Patricia Hartge and Purdue, \{Mark P.\} and Birmann, \{Brenda M.\} and Armstrong, \{Bruce K.\} and Pierluigi Cocco and Yawei Zhang and Gianluca Severi and Anne Zeleniuch-Jacquotte and Charles Lawrence and Laurie Burdette and Jeffrey Yuenger and Amy Hutchinson and Jacobs, \{Kevin B.\} and Call, \{Timothy G.\} and Shanafelt, \{Tait D.\} and Novak, \{Anne J.\} and Kay, \{Neil E.\} and Mark Liebow and Wang, \{Alice H.\} and Smedby, \{Karin E.\} and Adami, \{Hans Olov\} and Mads Melbye and Bengt Glimelius and Chang, \{Ellen T.\} and Martha Glenn and Karen Curtin and Cannon-Albright, \{Lisa A.\} and Brandt Jones and Diver, \{W. Ryan\} and Link, \{Brian K.\} and Weiner, \{George J.\} and Lucia Conde and Bracci, \{Paige M.\} and Jacques Riby and Holly, \{Elizabeth A.\} and Smith, \{Martyn T.\} and Jackson, \{Rebecca D.\} and Tinker, \{Lesley F.\} and Yolanda Benavente and Nikolaus Becker and Paolo Boffetta and Paul Brennan and Lenka Foretova and Marc Maynadie and James McKay and Anthony Staines and Rabe, \{Kari G.\} and Achenbach, \{Sara J.\} and Vachon, \{Celine M.\} and Goldin, \{Lynn R.\} and Strom, \{Sara S.\} and Lanasa, \{Mark C.\} and Spector, \{Logan G.\} and Leis, \{Jose F.\} and Cunningham, \{Julie M.\} and Weinberg, \{J. Brice\} and Morrison, \{Vicki A.\} and Caporaso, \{Neil E.\} and Norman, \{Aaron D.\} and Linet, \{Martha S.\} and \{De Roos\}, \{Anneclaire J.\} and Morton, \{Lindsay M.\} and Severson, \{Richard K.\} and Elio Riboli and Paolo Vineis and Rudolph Kaaks and Dimitrios Trichopoulos and Giovanna Masala and Elisabete Weiderpass and Chirlaque, \{Mar{\'i}a Dolores\} and Vermeulen, \{Roel C.H.\} and Travis, \{Ruth C.\} and Giles, \{Graham G.\} and Demetrius Albanes and Jarmo Virtamo and Stephanie Weinstein and Jacqueline Clavel and Tongzhang Zheng and Holford, \{Theodore R.\} and Kenneth Offit and Andrew Zelenetz and Klein, \{Robert J.\} and Spinelli, \{John J.\} and Bertrand, \{Kimberly A.\} and Francine Laden and Edward Giovannucci and Peter Kraft and Anne Kricker and Jenny Turner and Vajdic, \{Claire M.\} and Ennas, \{Maria Grazia\} and Ferri, \{Giovanni M.\} and Lucia Miligi and Liming Liang and Joshua Sampson and Simon Crouch and Park, \{Ju Hyun\} and North, \{Kari E.\} and Angela Cox and Snowden, \{John A.\} and Josh Wright and Angel Carracedo and Carlos Lopez-Otin and Silvia Bea and Itziar Salaverria and David Martin-Garcia and Elias Campo and Fraumeni, \{Joseph F.\} and \{De Sanjose\}, Silvia and Henrik Hjalgrim and Cerhan, \{James R.\} and Chanock, \{Stephen J.\} and Nathaniel Rothman and Slager, \{Susan L.\}",

year = "2013",

month = aug,

doi = "10.1038/ng.2652",

language = "English",

volume = "45",

pages = "868--876",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "8",

}

Berndt, SI, Skibola, CF, Joseph, V, Camp, NJ, Nieters, A, Wang, Z, Cozen, W, Monnereau, A, Wang, SS, Kelly, RS, Lan, Q, Teras, LR, Chatterjee, N, Chung, CC, Yeager, M, Brooks-Wilson, AR, Hartge, P, Purdue, MP, Birmann, BM, Armstrong, BK, Cocco, P, Zhang, Y, Severi, G, Zeleniuch-Jacquotte, A, Lawrence, C, Burdette, L, Yuenger, J, Hutchinson, A, Jacobs, KB, Call, TG, Shanafelt, TD, Novak, AJ, Kay, NE, Liebow, M, Wang, AH, Smedby, KE, Adami, HO, Melbye, M, Glimelius, B, Chang, ET, Glenn, M, Curtin, K, Cannon-Albright, LA, Jones, B, Diver, WR, Link, BK, Weiner, GJ, Conde, L, Bracci, PM, Riby, J, Holly, EA, Smith, MT, Jackson, RD, Tinker, LF, Benavente, Y, Becker, N, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, McKay, J, Staines, A, Rabe, KG, Achenbach, SJ, Vachon, CM, Goldin, LR, Strom, SS, Lanasa, MC, Spector, LG, Leis, JF, Cunningham, JM, Weinberg, JB, Morrison, VA, Caporaso, NE, Norman, AD, Linet, MS, De Roos, AJ, Morton, LM, Severson, RK, Riboli, E, Vineis, P, Kaaks, R, Trichopoulos, D, Masala, G, Weiderpass, E, Chirlaque, MD, Vermeulen, RCH, Travis, RC, Giles, GG, Albanes, D, Virtamo, J, Weinstein, S, Clavel, J, Zheng, T, Holford, TR, Offit, K, Zelenetz, A, Klein, RJ, Spinelli, JJ, Bertrand, KA, Laden, F, Giovannucci, E, Kraft, P, Kricker, A, Turner, J, Vajdic, CM, Ennas, MG, Ferri, GM, Miligi, L, Liang, L, Sampson, J, Crouch, S, Park, JH, North, KE, Cox, A, Snowden, JA, Wright, J, Carracedo, A, Lopez-Otin, C, Bea, S, Salaverria, I, Martin-Garcia, D, Campo, E, Fraumeni, JF, De Sanjose, S, Hjalgrim, H, Cerhan, JR, Chanock, SJ, Rothman, N & Slager, SL 2013, 'Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia', Nature Genetics, vol. 45, no. 8, pp. 868-876. https://doi.org/10.1038/ng.2652

TY - JOUR

T1 - Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

AU - Berndt, Sonja I.

AU - Skibola, Christine F.

AU - Joseph, Vijai

AU - Camp, Nicola J.

AU - Nieters, Alexandra

AU - Wang, Zhaoming

AU - Cozen, Wendy

AU - Monnereau, Alain

AU - Wang, Sophia S.

AU - Kelly, Rachel S.

AU - Lan, Qing

AU - Teras, Lauren R.

AU - Chatterjee, Nilanjan

AU - Chung, Charles C.

AU - Yeager, Meredith

AU - Brooks-Wilson, Angela R.

AU - Hartge, Patricia

AU - Purdue, Mark P.

AU - Birmann, Brenda M.

AU - Armstrong, Bruce K.

AU - Cocco, Pierluigi

AU - Zhang, Yawei

AU - Severi, Gianluca

AU - Zeleniuch-Jacquotte, Anne

AU - Lawrence, Charles

AU - Burdette, Laurie

AU - Yuenger, Jeffrey

AU - Hutchinson, Amy

AU - Jacobs, Kevin B.

AU - Call, Timothy G.

AU - Shanafelt, Tait D.

AU - Novak, Anne J.

AU - Kay, Neil E.

AU - Liebow, Mark

AU - Wang, Alice H.

AU - Smedby, Karin E.

AU - Adami, Hans Olov

AU - Melbye, Mads

AU - Glimelius, Bengt

AU - Chang, Ellen T.

AU - Glenn, Martha

AU - Curtin, Karen

AU - Cannon-Albright, Lisa A.

AU - Jones, Brandt

AU - Diver, W. Ryan

AU - Link, Brian K.

AU - Weiner, George J.

AU - Conde, Lucia

AU - Bracci, Paige M.

AU - Riby, Jacques

AU - Holly, Elizabeth A.

AU - Smith, Martyn T.

AU - Jackson, Rebecca D.

AU - Tinker, Lesley F.

AU - Benavente, Yolanda

AU - Becker, Nikolaus

AU - Boffetta, Paolo

AU - Brennan, Paul

AU - Foretova, Lenka

AU - Maynadie, Marc

AU - McKay, James

AU - Staines, Anthony

AU - Rabe, Kari G.

AU - Achenbach, Sara J.

AU - Vachon, Celine M.

AU - Goldin, Lynn R.

AU - Strom, Sara S.

AU - Lanasa, Mark C.

AU - Spector, Logan G.

AU - Leis, Jose F.

AU - Cunningham, Julie M.

AU - Weinberg, J. Brice

AU - Morrison, Vicki A.

AU - Caporaso, Neil E.

AU - Norman, Aaron D.

AU - Linet, Martha S.

AU - De Roos, Anneclaire J.

AU - Morton, Lindsay M.

AU - Severson, Richard K.

AU - Riboli, Elio

AU - Vineis, Paolo

AU - Kaaks, Rudolph

AU - Trichopoulos, Dimitrios

AU - Masala, Giovanna

AU - Weiderpass, Elisabete

AU - Chirlaque, María Dolores

AU - Vermeulen, Roel C.H.

AU - Travis, Ruth C.

AU - Giles, Graham G.

AU - Albanes, Demetrius

AU - Virtamo, Jarmo

AU - Weinstein, Stephanie

AU - Clavel, Jacqueline

AU - Zheng, Tongzhang

AU - Holford, Theodore R.

AU - Offit, Kenneth

AU - Zelenetz, Andrew

AU - Klein, Robert J.

AU - Spinelli, John J.

AU - Bertrand, Kimberly A.

AU - Laden, Francine

AU - Giovannucci, Edward

AU - Kraft, Peter

AU - Kricker, Anne

AU - Turner, Jenny

AU - Vajdic, Claire M.

AU - Ennas, Maria Grazia

AU - Ferri, Giovanni M.

AU - Miligi, Lucia

AU - Liang, Liming

AU - Sampson, Joshua

AU - Crouch, Simon

AU - Park, Ju Hyun

AU - North, Kari E.

AU - Cox, Angela

AU - Snowden, John A.

AU - Wright, Josh

AU - Carracedo, Angel

AU - Lopez-Otin, Carlos

AU - Bea, Silvia

AU - Salaverria, Itziar

AU - Martin-Garcia, David

AU - Campo, Elias

AU - Fraumeni, Joseph F.

AU - De Sanjose, Silvia

AU - Hjalgrim, Henrik

AU - Cerhan, James R.

AU - Chanock, Stephen J.

AU - Rothman, Nathaniel

AU - Slager, Susan L.

PY - 2013/8

Y1 - 2013/8

N2 - Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10-14), 18q21.33 (BCL2, P = 7.76 × 10-11), 11p15.5 (C11orf21, P = 2.15 × 10 -10), 4q25 (LEF1, P = 4.24 × 10-10), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 × 10-9), 9p21.3 (CDKN2B-AS1, P = 1.27 × 10-8), 18q21.32 (PMAIP1, P = 2.51 × 10 -8), 15q15.1 (BMF, P = 2.71 × 10-10) and 2p22.2 (QPCT, P = 1.68 × 10-8), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 × 10-18). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 × 10-8) and 5p15.33 (TERT, P = 1.92 × 10-7). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.

AB - Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10-14), 18q21.33 (BCL2, P = 7.76 × 10-11), 11p15.5 (C11orf21, P = 2.15 × 10 -10), 4q25 (LEF1, P = 4.24 × 10-10), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 × 10-9), 9p21.3 (CDKN2B-AS1, P = 1.27 × 10-8), 18q21.32 (PMAIP1, P = 2.51 × 10 -8), 15q15.1 (BMF, P = 2.71 × 10-10) and 2p22.2 (QPCT, P = 1.68 × 10-8), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 × 10-18). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 × 10-8) and 5p15.33 (TERT, P = 1.92 × 10-7). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.

UR - https://www.scopus.com/pages/publications/84881023533

U2 - 10.1038/ng.2652

DO - 10.1038/ng.2652

M3 - Article

C2 - 23770605

AN - SCOPUS:84881023533

SN - 1061-4036

VL - 45

SP - 868

EP - 876

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -

Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

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