Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

Sonja I. Berndt; Nicola J. Camp; Christine F. Skibola; Joseph Vijai; Zhaoming Wang; Jian Gu; Alexandra Nieters; Rachel S. Kelly; Karin E. Smedby; Alain Monnereau; Wendy Cozen; Angela Cox; Sophia S. Wang; Qing Lan; Lauren R. Teras; Moara Machado; Meredith Yeager; Angela R. Brooks-Wilson; Patricia Hartge; Mark P. Purdue; Brenda M. Birmann; Claire M. Vajdic; Pierluigi Cocco; Yawei Zhang; Graham G. Giles; Anne Zeleniuch-Jacquotte; Charles Lawrence; Rebecca Montalvan; Laurie Burdett; Amy Hutchinson; Yuanqing Ye; Timothy G. Call; Tait D. Shanafelt; Anne J. Novak; Neil E. Kay; Mark Liebow; Julie M. Cunningham; Cristine Allmer; Henrik Hjalgrim; Hans Olov Adami; Mads Melbye; Bengt Glimelius; Ellen T. Chang; Martha Glenn; Karen Curtin; Lisa A. Cannon-Albright; W. Ryan Diver; Brian K. Link; George J. Weiner; Lucia Conde; Paige M. Bracci; Jacques Riby; Donna K. Arnett; Degui Zhi; Justin M. Leach; Elizabeth A. Holly; Rebecca D. Jackson; Lesley F. Tinker; Yolanda Benavente; Nuria Sala; Delphine Casabonne; Nikolaus Becker; Paolo Boffetta; Paul Brennan; Lenka Foretova; Marc Maynadie; James McKay; Anthony Staines; Kari G. Chaffee; Sara J. Achenbach; Celine M. Vachon; Lynn R. Goldin; Sara S. Strom; Jose F. Leis; J. Brice Weinberg; Neil E. Caporaso; Aaron D. Norman; Anneclaire J. De Roos; Lindsay M. Morton; Richard K. Severson; Elio Riboli; Paolo Vineis; Rudolph Kaaks; Giovanna Masala; Elisabete Weiderpass; Maria Dolores Chirlaque; Roel C.H. Vermeulen; Ruth C. Travis; Melissa C. Southey; Roger L. Milne; Demetrius Albanes; Jarmo Virtamo; Stephanie Weinstein; Jacqueline Clavel; Tongzhang Zheng; Theodore R. Holford; Danylo J. Villano; Ann Maria; John J. Spinelli; Randy D. Gascoyne; Joseph M. Connors; Kimberly A. Bertrand; Edward Giovannucci; Peter Kraft; Anne Kricker; Jenny Turner; Maria Grazia Ennas; Giovanni M. Ferri; Lucia Miligi; Liming Liang; Baoshan Ma; Jinyan Huang; Simon Crouch; Ju Hyun Park; Nilanjan Chatterjee; Kari E. North; John A. Snowden; Josh Wright; Joseph F. Fraumeni; Kenneth Offit; Xifeng Wu; Silvia De Sanjose; James R. Cerhan; Stephen J. Chanock; Nathaniel Rothman; Susan L. Slager

doi:10.1038/ncomms10933

Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

Sonja I. Berndt, Nicola J. Camp, Christine F. Skibola, Joseph Vijai, Zhaoming Wang, Jian Gu, Alexandra Nieters, Rachel S. Kelly, Karin E. Smedby, Alain Monnereau, Wendy Cozen, Angela Cox, Sophia S. Wang, Qing Lan, Lauren R. Teras, Moara Machado, Meredith Yeager, Angela R. Brooks-Wilson, Patricia Hartge, Mark P. PurdueBrenda M. Birmann, Claire M. Vajdic, Pierluigi Cocco, Yawei Zhang, Graham G. Giles, Anne Zeleniuch-Jacquotte, Charles Lawrence, Rebecca Montalvan, Laurie Burdett, Amy Hutchinson, Yuanqing Ye, Timothy G. Call, Tait D. Shanafelt, Anne J. Novak, Neil E. Kay, Mark Liebow, Julie M. Cunningham, Cristine Allmer, Henrik Hjalgrim, Hans Olov Adami, Mads Melbye, Bengt Glimelius, Ellen T. Chang, Martha Glenn, Karen Curtin, Lisa A. Cannon-Albright, W. Ryan Diver, Brian K. Link, George J. Weiner, Lucia Conde, Paige M. Bracci, Jacques Riby, Donna K. Arnett, Degui Zhi, Justin M. Leach, Elizabeth A. Holly, Rebecca D. Jackson, Lesley F. Tinker, Yolanda Benavente, Nuria Sala, Delphine Casabonne, Nikolaus Becker, Paolo Boffetta, Paul Brennan, Lenka Foretova, Marc Maynadie, James McKay, Anthony Staines, Kari G. Chaffee, Sara J. Achenbach, Celine M. Vachon, Lynn R. Goldin, Sara S. Strom, Jose F. Leis, J. Brice Weinberg, Neil E. Caporaso, Aaron D. Norman, Anneclaire J. De Roos, Lindsay M. Morton, Richard K. Severson, Elio Riboli, Paolo Vineis, Rudolph Kaaks, Giovanna Masala, Elisabete Weiderpass, Maria Dolores Chirlaque, Roel C.H. Vermeulen, Ruth C. Travis, Melissa C. Southey, Roger L. Milne, Demetrius Albanes, Jarmo Virtamo, Stephanie Weinstein, Jacqueline Clavel, Tongzhang Zheng, Theodore R. Holford, Danylo J. Villano, Ann Maria, John J. Spinelli, Randy D. Gascoyne, Joseph M. Connors, Kimberly A. Bertrand, Edward Giovannucci, Peter Kraft, Anne Kricker, Jenny Turner, Maria Grazia Ennas, Giovanni M. Ferri, Lucia Miligi, Liming Liang, Baoshan Ma, Jinyan Huang, Simon Crouch, Ju Hyun Park, Nilanjan Chatterjee, Kari E. North, John A. Snowden, Josh Wright, Joseph F. Fraumeni, Kenneth Offit, Xifeng Wu, Silvia De Sanjose, James R. Cerhan, Stephen J. Chanock, Nathaniel Rothman, Susan L. Slager

Epidemiology

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

84 Scopus citations

Abstract

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10-11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10-8) and 3q28 (rs9815073, LPP, P=3.62 × 10-8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10-11) in the combined analysis. We find suggestive evidence (P<5 × 10-7) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10-8) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10-7). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.

Original language	English (US)
Article number	10933
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10933
State	Published - Mar 9 2016

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Access to Document

10.1038/ncomms10933

Cite this

Berndt, S. I., Camp, N. J., Skibola, C. F., Vijai, J., Wang, Z., Gu, J., Nieters, A., Kelly, R. S., Smedby, K. E., Monnereau, A., Cozen, W., Cox, A., Wang, S. S., Lan, Q., Teras, L. R., Machado, M., Yeager, M., Brooks-Wilson, A. R., Hartge, P., ... Slager, S. L. (2016). Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia. Nature communications, 7, Article 10933. https://doi.org/10.1038/ncomms10933

Berndt, SI, Camp, NJ, Skibola, CF, Vijai, J, Wang, Z, Gu, J, Nieters, A, Kelly, RS, Smedby, KE, Monnereau, A, Cozen, W, Cox, A, Wang, SS, Lan, Q, Teras, LR, Machado, M, Yeager, M, Brooks-Wilson, AR, Hartge, P, Purdue, MP, Birmann, BM, Vajdic, CM, Cocco, P, Zhang, Y, Giles, GG, Zeleniuch-Jacquotte, A, Lawrence, C, Montalvan, R, Burdett, L, Hutchinson, A, Ye, Y, Call, TG, Shanafelt, TD, Novak, AJ, Kay, NE, Liebow, M, Cunningham, JM, Allmer, C, Hjalgrim, H, Adami, HO, Melbye, M, Glimelius, B, Chang, ET, Glenn, M, Curtin, K, Cannon-Albright, LA, Diver, WR, Link, BK, Weiner, GJ, Conde, L, Bracci, PM, Riby, J, Arnett, DK, Zhi, D, Leach, JM, Holly, EA, Jackson, RD, Tinker, LF, Benavente, Y, Sala, N, Casabonne, D, Becker, N, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, McKay, J, Staines, A, Chaffee, KG, Achenbach, SJ, Vachon, CM, Goldin, LR, Strom, SS, Leis, JF, Weinberg, JB, Caporaso, NE, Norman, AD, De Roos, AJ, Morton, LM, Severson, RK, Riboli, E, Vineis, P, Kaaks, R, Masala, G, Weiderpass, E, Chirlaque, MD, Vermeulen, RCH, Travis, RC, Southey, MC, Milne, RL, Albanes, D, Virtamo, J, Weinstein, S, Clavel, J, Zheng, T, Holford, TR, Villano, DJ, Maria, A, Spinelli, JJ, Gascoyne, RD, Connors, JM, Bertrand, KA, Giovannucci, E, Kraft, P, Kricker, A, Turner, J, Ennas, MG, Ferri, GM, Miligi, L, Liang, L, Ma, B, Huang, J, Crouch, S, Park, JH, Chatterjee, N, North, KE, Snowden, JA, Wright, J, Fraumeni, JF, Offit, K, Wu, X, De Sanjose, S, Cerhan, JR, Chanock, SJ, Rothman, N & Slager, SL 2016, 'Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia', Nature communications, vol. 7, 10933. https://doi.org/10.1038/ncomms10933

@article{8de2281bb662421796dc79ad9f4be44f,

title = "Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia",

abstract = "Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10-11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10-8) and 3q28 (rs9815073, LPP, P=3.62 × 10-8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10-11) in the combined analysis. We find suggestive evidence (P<5 × 10-7) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10-8) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10-7). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.",

author = "Berndt, {Sonja I.} and Camp, {Nicola J.} and Skibola, {Christine F.} and Joseph Vijai and Zhaoming Wang and Jian Gu and Alexandra Nieters and Kelly, {Rachel S.} and Smedby, {Karin E.} and Alain Monnereau and Wendy Cozen and Angela Cox and Wang, {Sophia S.} and Qing Lan and Teras, {Lauren R.} and Moara Machado and Meredith Yeager and Brooks-Wilson, {Angela R.} and Patricia Hartge and Purdue, {Mark P.} and Birmann, {Brenda M.} and Vajdic, {Claire M.} and Pierluigi Cocco and Yawei Zhang and Giles, {Graham G.} and Anne Zeleniuch-Jacquotte and Charles Lawrence and Rebecca Montalvan and Laurie Burdett and Amy Hutchinson and Yuanqing Ye and Call, {Timothy G.} and Shanafelt, {Tait D.} and Novak, {Anne J.} and Kay, {Neil E.} and Mark Liebow and Cunningham, {Julie M.} and Cristine Allmer and Henrik Hjalgrim 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 Diver, {W. Ryan} and Link, {Brian K.} and Weiner, {George J.} and Lucia Conde and Bracci, {Paige M.} and Jacques Riby and Arnett, {Donna K.} and Degui Zhi and Leach, {Justin M.} and Holly, {Elizabeth A.} and Jackson, {Rebecca D.} and Tinker, {Lesley F.} and Yolanda Benavente and Nuria Sala and Delphine Casabonne and Nikolaus Becker and Paolo Boffetta and Paul Brennan and Lenka Foretova and Marc Maynadie and James McKay and Anthony Staines and Chaffee, {Kari G.} and Achenbach, {Sara J.} and Vachon, {Celine M.} and Goldin, {Lynn R.} and Strom, {Sara S.} and Leis, {Jose F.} and Weinberg, {J. Brice} and Caporaso, {Neil E.} and Norman, {Aaron D.} and {De Roos}, {Anneclaire J.} and Morton, {Lindsay M.} and Severson, {Richard K.} and Elio Riboli and Paolo Vineis and Rudolph Kaaks and Giovanna Masala and Elisabete Weiderpass and Chirlaque, {Maria Dolores} and Vermeulen, {Roel C.H.} and Travis, {Ruth C.} and Southey, {Melissa C.} and Milne, {Roger L.} and Demetrius Albanes and Jarmo Virtamo and Stephanie Weinstein and Jacqueline Clavel and Tongzhang Zheng and Holford, {Theodore R.} and Villano, {Danylo J.} and Ann Maria and Spinelli, {John J.} and Gascoyne, {Randy D.} and Connors, {Joseph M.} and Bertrand, {Kimberly A.} and Edward Giovannucci and Peter Kraft and Anne Kricker and Jenny Turner and Ennas, {Maria Grazia} and Ferri, {Giovanni M.} and Lucia Miligi and Liming Liang and Baoshan Ma and Jinyan Huang and Simon Crouch and Park, {Ju Hyun} and Nilanjan Chatterjee and North, {Kari E.} and Snowden, {John A.} and Josh Wright and Fraumeni, {Joseph F.} and Kenneth Offit and Xifeng Wu and {De Sanjose}, Silvia and Cerhan, {James R.} and Chanock, {Stephen J.} and Nathaniel Rothman and Slager, {Susan L.}",

note = "Funding Information: We thank I. Brock, K. Butterbach, A. Chabrier, D. Chan-Lam, D. Connley, H. Cramp, R. Cutting, C. Dalley, H. Dykes, A. Gabbas, P. Gaddam, P. Hui, L. Irish, L. Jacobus, S. Kaul, L. Klareskog, A. Lai, J. Lunde, M. McAdams, L. Padyukov, D. Parisi, V. Rajamanickam, T. Rattle, L. Rigacci, R. Sargent, G. Specchia, M. Stagner, P. Taylor, C. Tornow, J. WiIliams and G. Wood. The overall GWAS project was supported by the intramural programme of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health. ATBC—This research was supported in part by the Intramural Research Program of the NIH and the National Cancer Institute. In addition, this research was supported by US Public Health Service contracts N01-CN-45165, N01-RC-45035, N01-RC-37004 and HHSN261201000006C from the National Cancer Institute, Department of Health and Human Services. BC—This reasearch was supported by Canadian Institutes for Health Research (CIHR), Canadian Cancer Society and Michael Smith Foundation for Health Research. CPS-II—The Cancer Prevention Study-II (CPS-II) Nutrition Cohort is supported by the American Cancer Society. Genotyping for all CPS-II samples were supported by the Intramural Research Program of the NIH, NCI, Division of Cancer Epidemiology and Genetics. We acknowledge the contribution to this study from Central Cancer Registries supported by the Centers for Disease Control and Prevention National Program of Cancer Registries, and cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. ELCCS—This study was supported by Leukaemia & Lymphoma Research. ENGELA—This research was supported by Association pour la Recherche contre le Cancer (ARC), Institut National du Cancer (INCa), Fondation de France, Fondation contre la Leuce´mie, Agence nationale de se´curite´ sanitaire de l{\textquoteright}alimentation, de l{\textquoteright}environnement et du travail (ANSES). EPIC—This study was supported by Coordinated Action (contract no. 006438, SP23-CT-2005-006438); HuGeF (Human Genetics Foundation), Torino, Italy, and Cancer Research UK. EpiLymph— This study was supported by European Commission (grant references QLK4-CT-2000- 00422 and FOOD-CT-2006-023103), the Spanish Ministry of Health (grant references CIBERESP, PI11/01810, PI14/01219, RCESP C03/09, RTICESP C03/10 and RTIC RD06/0020/0095), the Marato´ de TV3 Foundation (grant reference 051210), the Age`ncia de Gestio´d{\textquoteright}AjutsUniversitarisi de Recerca—Generalitat de Catalunya (grant reference 2014SRG756) who had no role in the data collection, analysis or interpretation of the results, the NIH (contract NO1-CO-12400), the Compagnia di San Paolo—Programma Oncologia, the Federal Office for Radiation Protection grants StSch4261 and StSch4420, the Jose´ Carreras Leukemia Foundation grant DJCLS-R12/23, the German Federal Ministry for Education and Research (BMBF-01-EO-1303), the Health Research Board, Ireland and Cancer Research Ireland, Czech Republic supported by MH CZ—DRO (MMCI, 00209805) and RECAMO, CZ.1.05/2.1.00/03.0101, and Fondation de France and Association de Recherche Contre le Cancer. GEC/Mayo GWAS—This reaearch was supported by NIH (grant numbers CA118444, CA148690 and CA92153), Intramural Research Program of the NIH, National Cancer Institute and Veterans Affairs Research Service. Data collection for Duke University was supported by a Leukemia & Lymphoma Society Career Development Award, the Bernstein Family Fund for Leukemia and Lymphoma Research, the NIH (K08CA134919) and National Center for Advancing Translational Science (UL1 TR000135). HPFS—HPFS was supported in part by NIH grants CA167552, CA149445, CA098122, CA098566 and K07 CA115687. We thank the participants and staff of the Health Professionals Follow-up Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. We assume full responsibility for analyses and interpretation of these data. Iowa-Mayo SPORE— This was supported by NCI Specialized Programs of Research Excellence (SPORE) in Human Cancer (P50 CA97274), National Cancer Institute (30 CA086862 and P30 CA15083) and Henry J. Predolin Foundation. Italian GxE— This was supported by Italian Association for Cancer Research (AIRC, Investigator Grant 11855, P.C.), Fondazione Banco di Sardegna 2010-2012 and Regione Autonoma della Sardegna (LR7 CRP-59812/2012, M.G.E.). Mayo Clinic Case-Control—It was supported by NIH (R01 CA92153) and National Cancer Institute (P30 CA015083). MCCS—The Melbourne Collaborative Cohort Study (MCCS) recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553 and 504711, and also by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR). MCC-Spain—This study is funded by The Instituto de Salud Carlos III (ISCIII—Spanish Government, PI11/01810, PI14/01219, RCESP C03/09 and CIBERESP) and the Agencia de Gestio d{\textquoteright}Ajuts Universitaris i de Recerca (AGAUR)—Generalitat de Catalunya (Catalonian Government, 2014SGR756). Nadia Garcı´a and Marleny Vergara (ICO-IDIBELL) provided technical support for this study. MD Anderson provided Institutional support to the Center for Translational and Public Health Genomics. MSKCC—Geoffrey Beene Cancer Research Grant, Lymphoma Foundation (LF5541); Barbara K. Lipman Lymphoma Research Fund (74419); Robert and Kate Niehaus Clinical Cancer Genetics Research Initiative (57470); U01 HG007033; ENCODE and U01 HG007033. NCI-SEER—Intramural Research Program of the National Cancer Institute, NIH, and Public Health Service (N01-PC-65064,N01-PC-67008, N01-PC-67009, N01-PC-67010 and N02-PC-71105). NHS—The NHS was supported in part by NIH grants CA186107, CA87969, CA49449, CA149445, CA098122, CA098566 and K07 CA115687. We thank the participants and staff of the Nurses{\textquoteright} Health Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. We assume full responsibility for analyses and interpretation of these data. NSW—NSW was supported by grants from the Australian National Health and Medical Research Council (ID990920), the Cancer Council NSW and the University of Sydney Faculty of Medicine. NYU-WHS—National Cancer Institute (R01 CA098661, P30 CA016087) and National Institute of Environmental Health Sciences (ES000260). PLCO—This research was supported by the Intramural Research Program of the National Cancer Institute and by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. SCALE—Swedish Cancer Society (2009/659). Stockholm County Council (20110209) and the Strategic Research Program in Epidemiology at Karolinska Institute. Swedish Cancer Society grant (02 6661). NIH (5R01 CA69669-02), Plan Denmark. UCSF2—The UCSF studies were supported by the NCI, NIH (CA1046282 and CA154643). The collection of cancer incidence data used in this study was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute{\textquoteright}s Surveillance, Epidemiology, and End Results Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California and contract HHSN261201000034C awarded to the Public Health Institute; and the Centers for Disease Control and Prevention{\textquoteright}s National Program of Cancer Registries, under agreement no. 1U58 DP000807-01 awarded to the Public Health Institute. UTAH/Sheffield— NIH CA134674. Partial support for data collection at the Utah site was made possible by the Utah Population Database (UPDB) and the Utah Cancer Registry (UCR). Partial support for all data sets within the UPDB is provided by the Huntsman Cancer Institute (HCI) and the HCI Cancer Center Support grant, P30 CA42014. The UCR is supported in part by NIH contract HHSN261201000026C from the National Cancer Institute SEER Program with additional support from the Utah State Department of Health and the University of Utah. Partial support for data collection in Sheffield, UK was made possible by funds from Yorkshire Cancer Research and the Sheffield Experimental Cancer Medicine Centre. We thank the NCRI Haemato-oncology Clinical Studies Group, colleagues in the North Trent Cancer Network the North Trent Haemato-oncology Database. WHI—The investigators of WHI are as follows: Program Office (National Heart, Lung, and Blood Institute, Bethesda, MD, USA) Jacques Rossouw, Shari Ludlam, Dale Burwen, Joan McGowan, Leslie Ford and Nancy Geller; Clinical Coordinating Center (Fred Hutchinson Cancer Research Center, Seattle, WA, USA) Garnet Anderson, Ross Prentice, Andrea LaCroix and Charles Kooperberg; Investigators and Academic Centers (Brigham and Women{\textquoteright}s Hospital, Harvard Medical School, Boston, MA, USA) JoAnn E. Manson; (MedStar Health Research Institute/Howard University, Washington, DC, USA) Barbara V. Howard; (Stanford Prevention Research Center, Stanford, CA, USA) Marcia L. Stefanick; (The Ohio State University, Columbus, OH, USA) Rebecca Jackson; (University of Arizona, Tucson/Phoenix, AZ, USA) Cynthia A. Thomson; (University at Buffalo, Buffalo, NY, USA) Jean Wactawski-Wende; (University of Florida, Gainesville/Jacksonville, FL, USA) Marian Limacher; (University of Iowa, Iowa City/Davenport, IA, USA) Robert Wallace; (University of Pittsburgh, Pittsburgh, PA, USA) Lewis Kuller; (Wake Forest University School of Medicine, Winston-Salem, NC, USA) Sally Shumaker; and Women{\textquoteright}s Health Initiative Memory Study (Wake Forest University School of Medicine, Winston-Salem, NC, USA) Sally Shumaker. The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, US Department of Health and Human Services by contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C and HHSN271201100004C. YALE—National Cancer Institute (CA62006 and CA165923). Other support includes: NSFC—the National Natural Science Foundation of China (no. 61471078).",

year = "2016",

month = mar,

day = "9",

doi = "10.1038/ncomms10933",

language = "English (US)",

volume = "7",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

AU - Berndt, Sonja I.

AU - Camp, Nicola J.

AU - Skibola, Christine F.

AU - Vijai, Joseph

AU - Wang, Zhaoming

AU - Gu, Jian

AU - Nieters, Alexandra

AU - Kelly, Rachel S.

AU - Smedby, Karin E.

AU - Monnereau, Alain

AU - Cozen, Wendy

AU - Cox, Angela

AU - Wang, Sophia S.

AU - Lan, Qing

AU - Teras, Lauren R.

AU - Machado, Moara

AU - Yeager, Meredith

AU - Brooks-Wilson, Angela R.

AU - Hartge, Patricia

AU - Purdue, Mark P.

AU - Birmann, Brenda M.

AU - Vajdic, Claire M.

AU - Cocco, Pierluigi

AU - Zhang, Yawei

AU - Giles, Graham G.

AU - Zeleniuch-Jacquotte, Anne

AU - Lawrence, Charles

AU - Montalvan, Rebecca

AU - Burdett, Laurie

AU - Hutchinson, Amy

AU - Ye, Yuanqing

AU - Call, Timothy G.

AU - Shanafelt, Tait D.

AU - Novak, Anne J.

AU - Kay, Neil E.

AU - Liebow, Mark

AU - Cunningham, Julie M.

AU - Allmer, Cristine

AU - Hjalgrim, Henrik

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 - Diver, W. Ryan

AU - Link, Brian K.

AU - Weiner, George J.

AU - Conde, Lucia

AU - Bracci, Paige M.

AU - Riby, Jacques

AU - Arnett, Donna K.

AU - Zhi, Degui

AU - Leach, Justin M.

AU - Holly, Elizabeth A.

AU - Jackson, Rebecca D.

AU - Tinker, Lesley F.

AU - Benavente, Yolanda

AU - Sala, Nuria

AU - Casabonne, Delphine

AU - Becker, Nikolaus

AU - Boffetta, Paolo

AU - Brennan, Paul

AU - Foretova, Lenka

AU - Maynadie, Marc

AU - McKay, James

AU - Staines, Anthony

AU - Chaffee, Kari G.

AU - Achenbach, Sara J.

AU - Vachon, Celine M.

AU - Goldin, Lynn R.

AU - Strom, Sara S.

AU - Leis, Jose F.

AU - Weinberg, J. Brice

AU - Caporaso, Neil E.

AU - Norman, Aaron D.

AU - De Roos, Anneclaire J.

AU - Morton, Lindsay M.

AU - Severson, Richard K.

AU - Riboli, Elio

AU - Vineis, Paolo

AU - Kaaks, Rudolph

AU - Masala, Giovanna

AU - Weiderpass, Elisabete

AU - Chirlaque, Maria Dolores

AU - Vermeulen, Roel C.H.

AU - Travis, Ruth C.

AU - Southey, Melissa C.

AU - Milne, Roger L.

AU - Albanes, Demetrius

AU - Virtamo, Jarmo

AU - Weinstein, Stephanie

AU - Clavel, Jacqueline

AU - Zheng, Tongzhang

AU - Holford, Theodore R.

AU - Villano, Danylo J.

AU - Maria, Ann

AU - Spinelli, John J.

AU - Gascoyne, Randy D.

AU - Connors, Joseph M.

AU - Bertrand, Kimberly A.

AU - Giovannucci, Edward

AU - Kraft, Peter

AU - Kricker, Anne

AU - Turner, Jenny

AU - Ennas, Maria Grazia

AU - Ferri, Giovanni M.

AU - Miligi, Lucia

AU - Liang, Liming

AU - Ma, Baoshan

AU - Huang, Jinyan

AU - Crouch, Simon

AU - Park, Ju Hyun

AU - Chatterjee, Nilanjan

AU - North, Kari E.

AU - Snowden, John A.

AU - Wright, Josh

AU - Fraumeni, Joseph F.

AU - Offit, Kenneth

AU - Wu, Xifeng

AU - De Sanjose, Silvia

AU - Cerhan, James R.

AU - Chanock, Stephen J.

AU - Rothman, Nathaniel

AU - Slager, Susan L.

N1 - Funding Information: We thank I. Brock, K. Butterbach, A. Chabrier, D. Chan-Lam, D. Connley, H. Cramp, R. Cutting, C. Dalley, H. Dykes, A. Gabbas, P. Gaddam, P. Hui, L. Irish, L. Jacobus, S. Kaul, L. Klareskog, A. Lai, J. Lunde, M. McAdams, L. Padyukov, D. Parisi, V. Rajamanickam, T. Rattle, L. Rigacci, R. Sargent, G. Specchia, M. Stagner, P. Taylor, C. Tornow, J. WiIliams and G. Wood. The overall GWAS project was supported by the intramural programme of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health. ATBC—This research was supported in part by the Intramural Research Program of the NIH and the National Cancer Institute. In addition, this research was supported by US Public Health Service contracts N01-CN-45165, N01-RC-45035, N01-RC-37004 and HHSN261201000006C from the National Cancer Institute, Department of Health and Human Services. BC—This reasearch was supported by Canadian Institutes for Health Research (CIHR), Canadian Cancer Society and Michael Smith Foundation for Health Research. CPS-II—The Cancer Prevention Study-II (CPS-II) Nutrition Cohort is supported by the American Cancer Society. Genotyping for all CPS-II samples were supported by the Intramural Research Program of the NIH, NCI, Division of Cancer Epidemiology and Genetics. We acknowledge the contribution to this study from Central Cancer Registries supported by the Centers for Disease Control and Prevention National Program of Cancer Registries, and cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. ELCCS—This study was supported by Leukaemia & Lymphoma Research. ENGELA—This research was supported by Association pour la Recherche contre le Cancer (ARC), Institut National du Cancer (INCa), Fondation de France, Fondation contre la Leuce´mie, Agence nationale de se´curite´ sanitaire de l’alimentation, de l’environnement et du travail (ANSES). EPIC—This study was supported by Coordinated Action (contract no. 006438, SP23-CT-2005-006438); HuGeF (Human Genetics Foundation), Torino, Italy, and Cancer Research UK. EpiLymph— This study was supported by European Commission (grant references QLK4-CT-2000- 00422 and FOOD-CT-2006-023103), the Spanish Ministry of Health (grant references CIBERESP, PI11/01810, PI14/01219, RCESP C03/09, RTICESP C03/10 and RTIC RD06/0020/0095), the Marato´ de TV3 Foundation (grant reference 051210), the Age`ncia de Gestio´d’AjutsUniversitarisi de Recerca—Generalitat de Catalunya (grant reference 2014SRG756) who had no role in the data collection, analysis or interpretation of the results, the NIH (contract NO1-CO-12400), the Compagnia di San Paolo—Programma Oncologia, the Federal Office for Radiation Protection grants StSch4261 and StSch4420, the Jose´ Carreras Leukemia Foundation grant DJCLS-R12/23, the German Federal Ministry for Education and Research (BMBF-01-EO-1303), the Health Research Board, Ireland and Cancer Research Ireland, Czech Republic supported by MH CZ—DRO (MMCI, 00209805) and RECAMO, CZ.1.05/2.1.00/03.0101, and Fondation de France and Association de Recherche Contre le Cancer. GEC/Mayo GWAS—This reaearch was supported by NIH (grant numbers CA118444, CA148690 and CA92153), Intramural Research Program of the NIH, National Cancer Institute and Veterans Affairs Research Service. Data collection for Duke University was supported by a Leukemia & Lymphoma Society Career Development Award, the Bernstein Family Fund for Leukemia and Lymphoma Research, the NIH (K08CA134919) and National Center for Advancing Translational Science (UL1 TR000135). HPFS—HPFS was supported in part by NIH grants CA167552, CA149445, CA098122, CA098566 and K07 CA115687. We thank the participants and staff of the Health Professionals Follow-up Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. We assume full responsibility for analyses and interpretation of these data. Iowa-Mayo SPORE— This was supported by NCI Specialized Programs of Research Excellence (SPORE) in Human Cancer (P50 CA97274), National Cancer Institute (30 CA086862 and P30 CA15083) and Henry J. Predolin Foundation. Italian GxE— This was supported by Italian Association for Cancer Research (AIRC, Investigator Grant 11855, P.C.), Fondazione Banco di Sardegna 2010-2012 and Regione Autonoma della Sardegna (LR7 CRP-59812/2012, M.G.E.). Mayo Clinic Case-Control—It was supported by NIH (R01 CA92153) and National Cancer Institute (P30 CA015083). MCCS—The Melbourne Collaborative Cohort Study (MCCS) recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553 and 504711, and also by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR). MCC-Spain—This study is funded by The Instituto de Salud Carlos III (ISCIII—Spanish Government, PI11/01810, PI14/01219, RCESP C03/09 and CIBERESP) and the Agencia de Gestio d’Ajuts Universitaris i de Recerca (AGAUR)—Generalitat de Catalunya (Catalonian Government, 2014SGR756). Nadia Garcı´a and Marleny Vergara (ICO-IDIBELL) provided technical support for this study. MD Anderson provided Institutional support to the Center for Translational and Public Health Genomics. MSKCC—Geoffrey Beene Cancer Research Grant, Lymphoma Foundation (LF5541); Barbara K. Lipman Lymphoma Research Fund (74419); Robert and Kate Niehaus Clinical Cancer Genetics Research Initiative (57470); U01 HG007033; ENCODE and U01 HG007033. NCI-SEER—Intramural Research Program of the National Cancer Institute, NIH, and Public Health Service (N01-PC-65064,N01-PC-67008, N01-PC-67009, N01-PC-67010 and N02-PC-71105). NHS—The NHS was supported in part by NIH grants CA186107, CA87969, CA49449, CA149445, CA098122, CA098566 and K07 CA115687. We thank the participants and staff of the Nurses’ Health Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. We assume full responsibility for analyses and interpretation of these data. NSW—NSW was supported by grants from the Australian National Health and Medical Research Council (ID990920), the Cancer Council NSW and the University of Sydney Faculty of Medicine. NYU-WHS—National Cancer Institute (R01 CA098661, P30 CA016087) and National Institute of Environmental Health Sciences (ES000260). PLCO—This research was supported by the Intramural Research Program of the National Cancer Institute and by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. SCALE—Swedish Cancer Society (2009/659). Stockholm County Council (20110209) and the Strategic Research Program in Epidemiology at Karolinska Institute. Swedish Cancer Society grant (02 6661). NIH (5R01 CA69669-02), Plan Denmark. UCSF2—The UCSF studies were supported by the NCI, NIH (CA1046282 and CA154643). The collection of cancer incidence data used in this study was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California and contract HHSN261201000034C awarded to the Public Health Institute; and the Centers for Disease Control and Prevention’s National Program of Cancer Registries, under agreement no. 1U58 DP000807-01 awarded to the Public Health Institute. UTAH/Sheffield— NIH CA134674. Partial support for data collection at the Utah site was made possible by the Utah Population Database (UPDB) and the Utah Cancer Registry (UCR). Partial support for all data sets within the UPDB is provided by the Huntsman Cancer Institute (HCI) and the HCI Cancer Center Support grant, P30 CA42014. The UCR is supported in part by NIH contract HHSN261201000026C from the National Cancer Institute SEER Program with additional support from the Utah State Department of Health and the University of Utah. Partial support for data collection in Sheffield, UK was made possible by funds from Yorkshire Cancer Research and the Sheffield Experimental Cancer Medicine Centre. We thank the NCRI Haemato-oncology Clinical Studies Group, colleagues in the North Trent Cancer Network the North Trent Haemato-oncology Database. WHI—The investigators of WHI are as follows: Program Office (National Heart, Lung, and Blood Institute, Bethesda, MD, USA) Jacques Rossouw, Shari Ludlam, Dale Burwen, Joan McGowan, Leslie Ford and Nancy Geller; Clinical Coordinating Center (Fred Hutchinson Cancer Research Center, Seattle, WA, USA) Garnet Anderson, Ross Prentice, Andrea LaCroix and Charles Kooperberg; Investigators and Academic Centers (Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA) JoAnn E. Manson; (MedStar Health Research Institute/Howard University, Washington, DC, USA) Barbara V. Howard; (Stanford Prevention Research Center, Stanford, CA, USA) Marcia L. Stefanick; (The Ohio State University, Columbus, OH, USA) Rebecca Jackson; (University of Arizona, Tucson/Phoenix, AZ, USA) Cynthia A. Thomson; (University at Buffalo, Buffalo, NY, USA) Jean Wactawski-Wende; (University of Florida, Gainesville/Jacksonville, FL, USA) Marian Limacher; (University of Iowa, Iowa City/Davenport, IA, USA) Robert Wallace; (University of Pittsburgh, Pittsburgh, PA, USA) Lewis Kuller; (Wake Forest University School of Medicine, Winston-Salem, NC, USA) Sally Shumaker; and Women’s Health Initiative Memory Study (Wake Forest University School of Medicine, Winston-Salem, NC, USA) Sally Shumaker. The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, US Department of Health and Human Services by contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C and HHSN271201100004C. YALE—National Cancer Institute (CA62006 and CA165923). Other support includes: NSFC—the National Natural Science Foundation of China (no. 61471078).

PY - 2016/3/9

Y1 - 2016/3/9

N2 - Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10-11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10-8) and 3q28 (rs9815073, LPP, P=3.62 × 10-8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10-11) in the combined analysis. We find suggestive evidence (P<5 × 10-7) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10-8) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10-7). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.

AB - Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10-11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10-8) and 3q28 (rs9815073, LPP, P=3.62 × 10-8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10-11) in the combined analysis. We find suggestive evidence (P<5 × 10-7) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10-8) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10-7). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.

UR - http://www.scopus.com/inward/record.url?scp=84960517435&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84960517435&partnerID=8YFLogxK

U2 - 10.1038/ncomms10933

DO - 10.1038/ncomms10933

M3 - Article

C2 - 26956414

AN - SCOPUS:84960517435

SN - 2041-1723

VL - 7

JO - Nature communications

JF - Nature communications

M1 - 10933

ER -

Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

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