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; Núria 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; María-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 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, Núria 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, María-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

Sub Atmospheric Physics and Chemistry

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

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
Number of pages	9
Journal	Nature Communications [E]
Volume	7
DOIs	https://doi.org/10.1038/ncomms10933
Publication status	Published - 2016

Keywords

Adaptor Proteins, Signal Transducing
Apoptosis Regulatory Proteins
European Continental Ancestry Group
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Leukemia, Lymphocytic, Chronic, B-Cell
Membrane Proteins
Polymorphism, Single Nucleotide
Proto-Oncogene Proteins
Serpins
T-Box Domain Proteins

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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 [E], 7, Article 10933. https://doi.org/10.1038/ncomms10933

@article{5efc0c5ba87a40ffa97756b7188445c1,

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.",

keywords = "Adaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Membrane Proteins, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins, Serpins, T-Box Domain Proteins",

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 Hans-Olov Adami 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 N{\'u}ria 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 Mar{\'i}a-Dolores Chirlaque 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 Ju-Hyun Park 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",

doi = "10.1038/ncomms10933",

language = "English",

volume = "7",

journal = "Nature Communications [E]",

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, H-O, 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, M-D, 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, J-H, 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 [E], 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, Núria

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, María-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

Y1 - 2016

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.

KW - Adaptor Proteins, Signal Transducing

KW - Apoptosis Regulatory Proteins

KW - European Continental Ancestry Group

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Leukemia, Lymphocytic, Chronic, B-Cell

KW - Membrane Proteins

KW - Polymorphism, Single Nucleotide

KW - Proto-Oncogene Proteins

KW - Serpins

KW - T-Box Domain Proteins

U2 - 10.1038/ncomms10933

DO - 10.1038/ncomms10933

M3 - Article

C2 - 26956414

SN - 2041-1723

VL - 7

JO - Nature Communications [E]

JF - Nature Communications [E]

M1 - 10933

ER -

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

Abstract

Keywords

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