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 J. 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 Houlston, Susan L Slager

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 languageEnglish (US)
Article number14175
JournalNature Communications
Volume8
DOIs
StatePublished - Feb 6 2017

Fingerprint

leukemias
genome
Genome-Wide Association Study
immunity
B-Cell Chronic Lymphocytic Leukemia
loci
genes
Immunity
Genes
chromatin
determinants
Chromatin
Meta-Analysis
B-Lymphocytes
Transcription Factors
Cells
Genome
magnetic permeability

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

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

In: Nature Communications, Vol. 8, 14175, 06.02.2017.

Research output: Contribution to journalArticle

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, JJ, 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, R & Slager, SL 2017, 'Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia', Nature Communications, vol. 8, 14175. https://doi.org/10.1038/ncomms14175
Law, Philip J. ; Berndt, Sonja I. ; Speedy, Helen E. ; Camp, Nicola J. ; Sava, Georgina P. ; Skibola, Christine F. ; Holroyd, Amy ; Joseph, Vijai ; Sunter, Nicola J. ; Nieters, Alexandra ; Bea, Silvia ; Monnereau, Alain ; Martin-Garcia, David ; Goldin, Lynn R. ; Clot, Guillem ; Teras, Lauren R. ; Quintela, Inés ; Birmann, Brenda M. ; Jayne, Sandrine ; Cozen, Wendy ; Majid, Aneela ; Smedby, Karin E. ; Lan, Qing ; Dearden, Claire ; Brooks-Wilson, Angela R. ; Hall, Andrew G. ; Purdue, Mark P. ; Mainou-Fowler, Tryfonia ; Vajdic, Claire M. ; Jackson, Graham H. ; Cocco, Pierluigi ; Marr, Helen ; Zhang, Yawei ; Zheng, Tongzhang ; Giles, Graham G. ; Lawrence, Charles ; Call, Timothy G. ; Liebow, Mark ; Melbye, Mads ; Glimelius, Bengt ; Mansouri, Larry ; Glenn, Martha ; Curtin, Karen ; Diver, W. Ryan ; Link, Brian K. ; Conde, Lucia ; Bracci, Paige M. ; Holly, Elizabeth A. ; Jackson, Rebecca D. ; Tinker, Lesley F. ; Benavente, Yolanda ; Boffetta, Paolo ; Brennan, Paul ; Maynadie, Marc ; McKay, James ; Albanes, Demetrius ; Weinstein, Stephanie ; Wang, Zhaoming ; Caporaso, Neil E. ; Morton, Lindsay M. ; Severson, Richard K. ; Riboli, Elio ; Vineis, Paolo ; Vermeulen, Roel C H ; Southey, Melissa C. ; Milne, Roger L. ; Clavel, Jacqueline ; Topka, Sabine ; Spinelli, John J. ; Kraft, Peter ; Ennas, Maria Grazia ; Summerfield, Geoffrey ; Ferri, Giovanni M. ; Harris, Robert J. ; Miligi, Lucia ; Pettitt, Andrew R. ; North, Kari E. ; Allsup, David J. ; Fraumeni, Joseph F. ; Bailey, James R. ; Offit, Kenneth ; Pratt, Guy ; Hjalgrim, Henrik ; Pepper, Chris ; Chanock, Stephen J. ; Fegan, Chris ; Rosenquist, Richard ; De Sanjose, Silvia ; Carracedo, Angel ; Dyer, Martin J S ; Catovsky, Daniel ; Campo, Elias ; Cerhan, James R ; Allan, James M. ; Rothman, Nathanial ; Houlston, Richard ; Slager, Susan L. / Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia. In: Nature Communications. 2017 ; Vol. 8.
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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.",
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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 J.

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

AU - Slager, Susan L

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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.

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