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

Department of Statistics

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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
Article number	10933
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10933
State	Published - 9 Mar 2016

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10.1038/ncomms10933

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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

@article{23261442de604690a98f1a6f5c564371,

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.}",

year = "2016",

month = mar,

day = "9",

doi = "10.1038/ncomms10933",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

}

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

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.

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

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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