Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

Philip J Law; Sonja I. Berndt; Helen E Speedy; Nicola J Camp; Georgina P Sava; Christine F. Skibola; Amy Holroyd; Vijai Joseph; Nicola J Sunter; Alexandra Nieters; Silvia Bea; Alain Monnereau; David Martin-Garcia; Lynn R Goldin; Guillem Clot; Lauren R. Teras; Inés Quintela; Brenda M. Birmann; Sandrine Jayne; Wendy Cozen; Aneela Majid; Karin E Smedby; Qing Lan; Claire Dearden; Angela R. Brooks-Wilson; Andrew G Hall; Mark P. Purdue; Tryfonia Mainou-Fowler; Claire M. Vajdic; Graham H Jackson; Pierluigi Cocco; Helen Marr; Yawei Zhang; Tongzhang Zheng; Graham G. Giles; Charles Lawrence; Timothy G. Call; Mark Liebow; Mads Melbye; Bengt Glimelius; Larry Mansouri; Martha Glenn; Karen Curtin; W. Ryan Diver; Brian K. Link; Lucia Conde; Paige M. Bracci; Elizabeth A. Holly; Rebecca D. Jackson; Lesley F. Tinker; Yolanda Benavente; Paolo Boffetta; Paul Brennan; Marc Maynadie; James McKay; Demetrius Albanes; Stephanie Weinstein; Zhaoming Wang; Neil E Caporaso; Lindsay M. Morton; Richard K. Severson; Elio Riboli; Paolo Vineis; Roel C H Vermeulen; Melissa C. Southey; Roger L Milne; Jacqueline Clavel; Sabine Topka; John Spinelli; Peter Kraft; Maria Grazia Ennas; Geoffrey Summerfield; Giovanni M Ferri; Robert J Harris; Lucia Miligi; Andrew R Pettitt; Kari E. North; David J Allsup; Joseph F. Fraumeni; James R Bailey; Kenneth Offit; Guy Pratt; Henrik Hjalgrim; Chris Pepper; Stephen J. Chanock; Chris Fegan; Richard Rosenquist; Silvia De Sanjose; Angel Carracedo; Martin J S Dyer; Daniel Catovsky; Elias Campo; James R. Cerhan; James M Allan; Nathanial Rothman; Richard S Houlston; Susan L. Slager

doi:10.1038/ncomms14175

Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

Philip J Law, Sonja I. Berndt, Helen E Speedy, Nicola J Camp, Georgina P Sava, Christine F. Skibola, Amy Holroyd, Vijai Joseph, Nicola J Sunter, Alexandra Nieters, Silvia Bea, Alain Monnereau, David Martin-Garcia, Lynn R Goldin, Guillem Clot, Lauren R. Teras, Inés Quintela, Brenda M. Birmann, Sandrine Jayne, Wendy CozenAneela Majid, Karin E Smedby, Qing Lan, Claire Dearden, Angela R. Brooks-Wilson, Andrew G Hall, Mark P. Purdue, Tryfonia Mainou-Fowler, Claire M. Vajdic, Graham H Jackson, Pierluigi Cocco, Helen Marr, Yawei Zhang, Tongzhang Zheng, Graham G. Giles, Charles Lawrence, Timothy G. Call, Mark Liebow, Mads Melbye, Bengt Glimelius, Larry Mansouri, Martha Glenn, Karen Curtin, W. Ryan Diver, Brian K. Link, Lucia Conde, Paige M. Bracci, Elizabeth A. Holly, Rebecca D. Jackson, Lesley F. Tinker, Yolanda Benavente, Paolo Boffetta, Paul Brennan, Marc Maynadie, James McKay, Demetrius Albanes, Stephanie Weinstein, Zhaoming Wang, Neil E Caporaso, Lindsay M. Morton, Richard K. Severson, Elio Riboli, Paolo Vineis, Roel C H Vermeulen, Melissa C. Southey, Roger L Milne, Jacqueline Clavel, Sabine Topka, John Spinelli, Peter Kraft, Maria Grazia Ennas, Geoffrey Summerfield, Giovanni M Ferri, Robert J Harris, Lucia Miligi, Andrew R Pettitt, Kari E. North, David J Allsup, Joseph F. Fraumeni, James R Bailey, Kenneth Offit, Guy Pratt, Henrik Hjalgrim, Chris Pepper, Stephen J. Chanock, Chris Fegan, Richard Rosenquist, Silvia De Sanjose, Angel Carracedo, Martin J S Dyer, Daniel Catovsky, Elias Campo, James R. Cerhan, James M Allan, Nathanial Rothman, Richard S Houlston, Susan L. Slager

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

Abstract

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10-13), 1q42.13 (rs41271473, P=1.06 × 10-10), 4q24 (rs71597109, P=1.37 × 10-10), 4q35.1 (rs57214277, P=3.69 × 10-8), 6p21.31 (rs3800461, P=1.97 × 10-8), 11q23.2 (rs61904987, P=2.64 × 10-11), 18q21.1 (rs1036935, P=3.27 × 10-8), 19p13.3 (rs7254272, P=4.67 × 10-8) and 22q13.33 (rs140522, P=2.70 × 10-9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.

Original language	English
Pages (from-to)	14175
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms14175
Publication status	Published - 6 Feb 2017

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Law, P. J., Berndt, S. I., Speedy, H. E., Camp, N. J., Sava, G. P., Skibola, C. F., Holroyd, A., Joseph, V., Sunter, N. J., Nieters, A., Bea, S., Monnereau, A., Martin-Garcia, D., Goldin, L. R., Clot, G., Teras, L. R., Quintela, I., Birmann, B. M., Jayne, S., ... Slager, S. L. (2017). Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia. Nature Communications, 8, 14175. https://doi.org/10.1038/ncomms14175

@article{c83ec7aa7d20497e9863ac3e60585a01,

title = "Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia",

abstract = "Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10-13), 1q42.13 (rs41271473, P=1.06 × 10-10), 4q24 (rs71597109, P=1.37 × 10-10), 4q35.1 (rs57214277, P=3.69 × 10-8), 6p21.31 (rs3800461, P=1.97 × 10-8), 11q23.2 (rs61904987, P=2.64 × 10-11), 18q21.1 (rs1036935, P=3.27 × 10-8), 19p13.3 (rs7254272, P=4.67 × 10-8) and 22q13.33 (rs140522, P=2.70 × 10-9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.",

author = "Law, {Philip J} and Berndt, {Sonja I.} and Speedy, {Helen E} and Camp, {Nicola J} and Sava, {Georgina P} and Skibola, {Christine F.} and Amy Holroyd and Vijai Joseph and Sunter, {Nicola J} and Alexandra Nieters and Silvia Bea and Alain Monnereau and David Martin-Garcia and Goldin, {Lynn R} and Guillem Clot and Teras, {Lauren R.} and In{\'e}s Quintela and Birmann, {Brenda M.} and Sandrine Jayne and Wendy Cozen and Aneela Majid and Smedby, {Karin E} and Qing Lan and Claire Dearden and Brooks-Wilson, {Angela R.} and Hall, {Andrew G} and Purdue, {Mark P.} and Tryfonia Mainou-Fowler and Vajdic, {Claire M.} and Jackson, {Graham H} and Pierluigi Cocco and Helen Marr and Yawei Zhang and Tongzhang Zheng and Giles, {Graham G.} and Charles Lawrence and Call, {Timothy G.} and Mark Liebow and Mads Melbye and Bengt Glimelius and Larry Mansouri and Martha Glenn and Karen Curtin and Diver, {W. Ryan} and Link, {Brian K.} and Lucia Conde and Bracci, {Paige M.} and Holly, {Elizabeth A.} and Jackson, {Rebecca D.} and Tinker, {Lesley F.} and Yolanda Benavente and Paolo Boffetta and Paul Brennan and Marc Maynadie and James McKay and Demetrius Albanes and Stephanie Weinstein and Zhaoming Wang and Caporaso, {Neil E} and Morton, {Lindsay M.} and Severson, {Richard K.} and Elio Riboli and Paolo Vineis and Vermeulen, {Roel C H} and Southey, {Melissa C.} and Milne, {Roger L} and Jacqueline Clavel and Sabine Topka and John Spinelli and Peter Kraft and Ennas, {Maria Grazia} and Geoffrey Summerfield and Ferri, {Giovanni M} and Harris, {Robert J} and Lucia Miligi and Pettitt, {Andrew R} and North, {Kari E.} and Allsup, {David J} and Fraumeni, {Joseph F.} and Bailey, {James R} and Kenneth Offit and Guy Pratt and Henrik Hjalgrim and Chris Pepper and Chanock, {Stephen J.} and Chris Fegan and Richard Rosenquist and {De Sanjose}, Silvia and Angel Carracedo and Dyer, {Martin J S} and Daniel Catovsky and Elias Campo and Cerhan, {James R.} and Allan, {James M} and Nathanial Rothman and Houlston, {Richard S} and Slager, {Susan L.}",

year = "2017",

month = feb,

day = "6",

doi = "10.1038/ncomms14175",

language = "English",

volume = "8",

pages = "14175",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

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Law, PJ, Berndt, SI, Speedy, HE, Camp, NJ, Sava, GP, Skibola, CF, Holroyd, A, Joseph, V, Sunter, NJ, Nieters, A, Bea, S, Monnereau, A, Martin-Garcia, D, Goldin, LR, Clot, G, Teras, LR, Quintela, I, Birmann, BM, Jayne, S, Cozen, W, Majid, A, Smedby, KE, Lan, Q, Dearden, C, Brooks-Wilson, AR, Hall, AG, Purdue, MP, Mainou-Fowler, T, Vajdic, CM, Jackson, GH, Cocco, P, Marr, H, Zhang, Y, Zheng, T, Giles, GG, Lawrence, C, Call, TG, Liebow, M, Melbye, M, Glimelius, B, Mansouri, L, Glenn, M, Curtin, K, Diver, WR, Link, BK, Conde, L, Bracci, PM, Holly, EA, Jackson, RD, Tinker, LF, Benavente, Y, Boffetta, P, Brennan, P, Maynadie, M, McKay, J, Albanes, D, Weinstein, S, Wang, Z, Caporaso, NE, Morton, LM, Severson, RK, Riboli, E, Vineis, P, Vermeulen, RCH, Southey, MC, Milne, RL, Clavel, J, Topka, S, Spinelli, J, Kraft, P, Ennas, MG, Summerfield, G, Ferri, GM, Harris, RJ, Miligi, L, Pettitt, AR, North, KE, Allsup, DJ, Fraumeni, JF, Bailey, JR, Offit, K, Pratt, G, Hjalgrim, H, Pepper, C, Chanock, SJ, Fegan, C, Rosenquist, R, De Sanjose, S, Carracedo, A, Dyer, MJS, Catovsky, D, Campo, E, Cerhan, JR, Allan, JM, Rothman, N, Houlston, RS & Slager, SL 2017, 'Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia', Nature Communications, vol. 8, pp. 14175. https://doi.org/10.1038/ncomms14175

TY - JOUR

T1 - Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

AU - Law, Philip J

AU - Berndt, Sonja I.

AU - Speedy, Helen E

AU - Camp, Nicola J

AU - Sava, Georgina P

AU - Skibola, Christine F.

AU - Holroyd, Amy

AU - Joseph, Vijai

AU - Sunter, Nicola J

AU - Nieters, Alexandra

AU - Bea, Silvia

AU - Monnereau, Alain

AU - Martin-Garcia, David

AU - Goldin, Lynn R

AU - Clot, Guillem

AU - Teras, Lauren R.

AU - Quintela, Inés

AU - Birmann, Brenda M.

AU - Jayne, Sandrine

AU - Cozen, Wendy

AU - Majid, Aneela

AU - Smedby, Karin E

AU - Lan, Qing

AU - Dearden, Claire

AU - Brooks-Wilson, Angela R.

AU - Hall, Andrew G

AU - Purdue, Mark P.

AU - Mainou-Fowler, Tryfonia

AU - Vajdic, Claire M.

AU - Jackson, Graham H

AU - Cocco, Pierluigi

AU - Marr, Helen

AU - Zhang, Yawei

AU - Zheng, Tongzhang

AU - Giles, Graham G.

AU - Lawrence, Charles

AU - Call, Timothy G.

AU - Liebow, Mark

AU - Melbye, Mads

AU - Glimelius, Bengt

AU - Mansouri, Larry

AU - Glenn, Martha

AU - Curtin, Karen

AU - Diver, W. Ryan

AU - Link, Brian K.

AU - Conde, Lucia

AU - Bracci, Paige M.

AU - Holly, Elizabeth A.

AU - Jackson, Rebecca D.

AU - Tinker, Lesley F.

AU - Benavente, Yolanda

AU - Boffetta, Paolo

AU - Brennan, Paul

AU - Maynadie, Marc

AU - McKay, James

AU - Albanes, Demetrius

AU - Weinstein, Stephanie

AU - Wang, Zhaoming

AU - Caporaso, Neil E

AU - Morton, Lindsay M.

AU - Severson, Richard K.

AU - Riboli, Elio

AU - Vineis, Paolo

AU - Vermeulen, Roel C H

AU - Southey, Melissa C.

AU - Milne, Roger L

AU - Clavel, Jacqueline

AU - Topka, Sabine

AU - Spinelli, John

AU - Kraft, Peter

AU - Ennas, Maria Grazia

AU - Summerfield, Geoffrey

AU - Ferri, Giovanni M

AU - Harris, Robert J

AU - Miligi, Lucia

AU - Pettitt, Andrew R

AU - North, Kari E.

AU - Allsup, David J

AU - Fraumeni, Joseph F.

AU - Bailey, James R

AU - Offit, Kenneth

AU - Pratt, Guy

AU - Hjalgrim, Henrik

AU - Pepper, Chris

AU - Chanock, Stephen J.

AU - Fegan, Chris

AU - Rosenquist, Richard

AU - De Sanjose, Silvia

AU - Carracedo, Angel

AU - Dyer, Martin J S

AU - Catovsky, Daniel

AU - Campo, Elias

AU - Cerhan, James R.

AU - Allan, James M

AU - Rothman, Nathanial

AU - Houlston, Richard S

AU - Slager, Susan L.

PY - 2017/2/6

Y1 - 2017/2/6

N2 - Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10-13), 1q42.13 (rs41271473, P=1.06 × 10-10), 4q24 (rs71597109, P=1.37 × 10-10), 4q35.1 (rs57214277, P=3.69 × 10-8), 6p21.31 (rs3800461, P=1.97 × 10-8), 11q23.2 (rs61904987, P=2.64 × 10-11), 18q21.1 (rs1036935, P=3.27 × 10-8), 19p13.3 (rs7254272, P=4.67 × 10-8) and 22q13.33 (rs140522, P=2.70 × 10-9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.

AB - Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10-13), 1q42.13 (rs41271473, P=1.06 × 10-10), 4q24 (rs71597109, P=1.37 × 10-10), 4q35.1 (rs57214277, P=3.69 × 10-8), 6p21.31 (rs3800461, P=1.97 × 10-8), 11q23.2 (rs61904987, P=2.64 × 10-11), 18q21.1 (rs1036935, P=3.27 × 10-8), 19p13.3 (rs7254272, P=4.67 × 10-8) and 22q13.33 (rs140522, P=2.70 × 10-9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.

U2 - 10.1038/ncomms14175

DO - 10.1038/ncomms14175

M3 - Article

C2 - 28165464

SN - 2041-1723

VL - 8

SP - 14175

JO - Nature Communications

JF - Nature Communications

ER -

Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

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