Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

Sonja I. Berndt; Christine F. Skibola; Vijai Joseph; Nicola J. Camp; Alexandra Nieters; Zhaoming Wang; Wendy Cozen; Alain Monnereau; Sophia S. Wang; Rachel S. Kelly; Qing Lan; Lauren R. Teras; Nilanjan Chatterjee; Charles C. Chung; Meredith Yeager; Angela R. Brooks-Wilson; Patricia Hartge; Mark P. Purdue; Brenda M. Birmann; Bruce K. Armstrong; Pierluigi Cocco; Yawei Zhang; Gianluca Severi; Anne Zeleniuch-Jacquotte; Charles Lawrence; Laurie Burdette; Jeffrey Yuenger; Amy Hutchinson; Kevin B. Jacobs; Timothy G. Call; Tait D. Shanafelt; Anne J. Novak; Neil E. Kay; Mark Liebow; Alice H. Wang; Karin E. Smedby; Hans Olov Adami; Mads Melbye; Bengt Glimelius; Ellen T. Chang; Martha Glenn; Karen Curtin; Lisa A. Cannon-Albright; Brandt Jones; W. Ryan Diver; Brian K. Link; George J. Weiner; Lucia Conde; Paige M. Bracci; Jacques Riby; Elizabeth A. Holly; Martyn T. Smith; Rebecca D. Jackson; Lesley F. Tinker; Yolanda Benavente; Nikolaus Becker; Paolo Boffetta; Paul Brennan; Lenka Foretova; Marc Maynadie; James McKay; Anthony Staines; Kari G. Rabe; Sara J. Achenbach; Celine M. Vachon; Lynn R. Goldin; Sara S. Strom; Mark C. Lanasa; Logan G. Spector; Jose F. Leis; Julie M. Cunningham; J. Brice Weinberg; Vicki A. Morrison; Neil E. Caporaso; Aaron D. Norman; Martha S. Linet; Anneclaire J. De Roos; Lindsay M. Morton; Richard K. Severson; Elio Riboli; Paolo Vineis; Rudolph Kaaks; Dimitrios Trichopoulos; Giovanna Masala; Elisabete Weiderpass; María Dolores Chirlaque; Roel C.H. Vermeulen; Ruth C. Travis; Graham G. Giles; Demetrius Albanes; Jarmo Virtamo; Stephanie Weinstein; Jacqueline Clavel; Tongzhang Zheng; Theodore R. Holford; Kenneth Offit; Andrew Zelenetz; Robert J. Klein; John J. Spinelli; Kimberly A. Bertrand; Francine Laden; Edward Giovannucci; Peter Kraft; Anne Kricker; Jenny Turner; Claire M. Vajdic; Maria Grazia Ennas; Giovanni M. Ferri; Lucia Miligi; Liming Liang; Joshua Sampson; Simon Crouch; Ju Hyun Park; Kari E. North; Angela Cox; John A. Snowden; Josh Wright; Angel Carracedo; Carlos Lopez-Otin; Silvia Bea; Itziar Salaverria; David Martin-Garcia; Elias Campo; Joseph F. Fraumeni; Silvia De Sanjose; Henrik Hjalgrim; James R. Cerhan; Stephen J. Chanock; Nathaniel Rothman; Susan L. Slager

doi:10.1038/ng.2652

Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

Sonja I. Berndt, Christine F. Skibola, Vijai Joseph, Nicola J. Camp, Alexandra Nieters, Zhaoming Wang, Wendy Cozen, Alain Monnereau, Sophia S. Wang, Rachel S. Kelly, Qing Lan, Lauren R. Teras, Nilanjan Chatterjee, Charles C. Chung, Meredith Yeager, Angela R. Brooks-Wilson, Patricia Hartge, Mark P. Purdue, Brenda M. Birmann, Bruce K. ArmstrongPierluigi Cocco, Yawei Zhang, Gianluca Severi, Anne Zeleniuch-Jacquotte, Charles Lawrence, Laurie Burdette, Jeffrey Yuenger, Amy Hutchinson, Kevin B. Jacobs, Timothy G. Call, Tait D. Shanafelt, Anne J. Novak, Neil E. Kay, Mark Liebow, Alice H. Wang, Karin E. Smedby, Hans Olov Adami, Mads Melbye, Bengt Glimelius, Ellen T. Chang, Martha Glenn, Karen Curtin, Lisa A. Cannon-Albright, Brandt Jones, W. Ryan Diver, Brian K. Link, George J. Weiner, Lucia Conde, Paige M. Bracci, Jacques Riby, Elizabeth A. Holly, Martyn T. Smith, Rebecca D. Jackson, Lesley F. Tinker, Yolanda Benavente, Nikolaus Becker, Paolo Boffetta, Paul Brennan, Lenka Foretova, Marc Maynadie, James McKay, Anthony Staines, Kari G. Rabe, Sara J. Achenbach, Celine M. Vachon, Lynn R. Goldin, Sara S. Strom, Mark C. Lanasa, Logan G. Spector, Jose F. Leis, Julie M. Cunningham, J. Brice Weinberg, Vicki A. Morrison, Neil E. Caporaso, Aaron D. Norman, Martha S. Linet, Anneclaire J. De Roos, Lindsay M. Morton, Richard K. Severson, Elio Riboli, Paolo Vineis, Rudolph Kaaks, Dimitrios Trichopoulos, Giovanna Masala, Elisabete Weiderpass, María Dolores Chirlaque, Roel C.H. Vermeulen, Ruth C. Travis, Graham G. Giles, Demetrius Albanes, Jarmo Virtamo, Stephanie Weinstein, Jacqueline Clavel, Tongzhang Zheng, Theodore R. Holford, Kenneth Offit, Andrew Zelenetz, Robert J. Klein, John J. Spinelli, Kimberly A. Bertrand, Francine Laden, Edward Giovannucci, Peter Kraft, Anne Kricker, Jenny Turner, Claire M. Vajdic, Maria Grazia Ennas, Giovanni M. Ferri, Lucia Miligi, Liming Liang, Joshua Sampson, Simon Crouch, Ju Hyun Park, Kari E. North, Angela Cox, John A. Snowden, Josh Wright, Angel Carracedo, Carlos Lopez-Otin, Silvia Bea, Itziar Salaverria, David Martin-Garcia, Elias Campo, Joseph F. Fraumeni, Silvia De Sanjose, Henrik Hjalgrim, James R. Cerhan, Stephen J. Chanock, Nathaniel Rothman, Susan L. Slager^*

^*Corresponding author for this work

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

164 Citations (Scopus)

Abstract

Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10^-14), 18q21.33 (BCL2, P = 7.76 × 10^-11), 11p15.5 (C11orf21, P = 2.15 × 10 ^-10), 4q25 (LEF1, P = 4.24 × 10^-10), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 × 10^-9), 9p21.3 (CDKN2B-AS1, P = 1.27 × 10^-8), 18q21.32 (PMAIP1, P = 2.51 × 10 ^-8), 15q15.1 (BMF, P = 2.71 × 10^-10) and 2p22.2 (QPCT, P = 1.68 × 10^-8), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 × 10^-18). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 × 10^-8) and 5p15.33 (TERT, P = 1.92 × 10^-7). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.

Original language	English
Pages (from-to)	868-876
Number of pages	9
Journal	Nature Genetics
Volume	45
Issue number	8
DOIs	https://doi.org/10.1038/ng.2652
Publication status	Published - Aug 2013
Externally published	Yes

Bibliographical note

Funding Information:
We thank C. Allmer, E. Angelucci, A. Bigelow, I. Brock, K. Butterbach, A. Chabrier, D. Chan-Lam, J.M. Conners, D. Connley, M. Cornelis, K. Corsano, C. Dalley, D. Cox, H. Cramp, R. Cutting, H. Dykes, L. Ershler, A. Gabbas, R.P. Gallagher, R.D. Gascoyne, P. Hui, L. Irish, L. Jacobus, S. Kaul, J. Lunde, M. McAdams, R. Montalvan, M. Rais, T. Rattle, L. Rigacci, K. Snyder, G. Specchia, M. Stagner, P. Taylor, G. Thomas, C. Tornow, G. Wood, M. Yang and M. Zucca for their assistance. The overall GWAS project was supported by the intramural program of the Division of Cancer Epidemiology and Genetics, NCI, US National Institutes of Health. A full list of acknowledgments is provided in the Supplementary Note.

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10.1038/ng.2652

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Berndt, S. I., Skibola, C. F., Joseph, V., Camp, N. J., Nieters, A., Wang, Z., Cozen, W., Monnereau, A., Wang, S. S., Kelly, R. S., Lan, Q., Teras, L. R., Chatterjee, N., Chung, C. C., Yeager, M., Brooks-Wilson, A. R., Hartge, P., Purdue, M. P., Birmann, B. M., ... Slager, S. L. (2013). Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia. Nature Genetics, 45(8), 868-876. https://doi.org/10.1038/ng.2652

@article{43f9143042a94472a0f49e126c86887c,

title = "Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia",

abstract = "Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10-14), 18q21.33 (BCL2, P = 7.76 × 10-11), 11p15.5 (C11orf21, P = 2.15 × 10 -10), 4q25 (LEF1, P = 4.24 × 10-10), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 × 10-9), 9p21.3 (CDKN2B-AS1, P = 1.27 × 10-8), 18q21.32 (PMAIP1, P = 2.51 × 10 -8), 15q15.1 (BMF, P = 2.71 × 10-10) and 2p22.2 (QPCT, P = 1.68 × 10-8), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 × 10-18). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 × 10-8) and 5p15.33 (TERT, P = 1.92 × 10-7). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.",

author = "Berndt, {Sonja I.} and Skibola, {Christine F.} and Vijai Joseph and Camp, {Nicola J.} and Alexandra Nieters and Zhaoming Wang and Wendy Cozen and Alain Monnereau and Wang, {Sophia S.} and Kelly, {Rachel S.} and Qing Lan and Teras, {Lauren R.} and Nilanjan Chatterjee and Chung, {Charles C.} and Meredith Yeager and Brooks-Wilson, {Angela R.} and Patricia Hartge and Purdue, {Mark P.} and Birmann, {Brenda M.} and Armstrong, {Bruce K.} and Pierluigi Cocco and Yawei Zhang and Gianluca Severi and Anne Zeleniuch-Jacquotte and Charles Lawrence and Laurie Burdette and Jeffrey Yuenger and Amy Hutchinson and Jacobs, {Kevin B.} and Call, {Timothy G.} and Shanafelt, {Tait D.} and Novak, {Anne J.} and Kay, {Neil E.} and Mark Liebow and Wang, {Alice H.} and Smedby, {Karin E.} 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 Brandt Jones and Diver, {W. Ryan} and Link, {Brian K.} and Weiner, {George J.} and Lucia Conde and Bracci, {Paige M.} and Jacques Riby and Holly, {Elizabeth A.} and Smith, {Martyn T.} and Jackson, {Rebecca D.} and Tinker, {Lesley F.} and Yolanda Benavente and Nikolaus Becker and Paolo Boffetta and Paul Brennan and Lenka Foretova and Marc Maynadie and James McKay and Anthony Staines and Rabe, {Kari G.} and Achenbach, {Sara J.} and Vachon, {Celine M.} and Goldin, {Lynn R.} and Strom, {Sara S.} and Lanasa, {Mark C.} and Spector, {Logan G.} and Leis, {Jose F.} and Cunningham, {Julie M.} and Weinberg, {J. Brice} and Morrison, {Vicki A.} and Caporaso, {Neil E.} and Norman, {Aaron D.} and Linet, {Martha S.} and {De Roos}, {Anneclaire J.} and Morton, {Lindsay M.} and Severson, {Richard K.} and Elio Riboli and Paolo Vineis and Rudolph Kaaks and Dimitrios Trichopoulos and Giovanna Masala and Elisabete Weiderpass and Chirlaque, {Mar{\'i}a Dolores} and Vermeulen, {Roel C.H.} and Travis, {Ruth C.} and Giles, {Graham G.} and Demetrius Albanes and Jarmo Virtamo and Stephanie Weinstein and Jacqueline Clavel and Tongzhang Zheng and Holford, {Theodore R.} and Kenneth Offit and Andrew Zelenetz and Klein, {Robert J.} and Spinelli, {John J.} and Bertrand, {Kimberly A.} and Francine Laden and Edward Giovannucci and Peter Kraft and Anne Kricker and Jenny Turner and Vajdic, {Claire M.} and Ennas, {Maria Grazia} and Ferri, {Giovanni M.} and Lucia Miligi and Liming Liang and Joshua Sampson and Simon Crouch and Park, {Ju Hyun} and North, {Kari E.} and Angela Cox and Snowden, {John A.} and Josh Wright and Angel Carracedo and Carlos Lopez-Otin and Silvia Bea and Itziar Salaverria and David Martin-Garcia and Elias Campo and Fraumeni, {Joseph F.} and {De Sanjose}, Silvia and Henrik Hjalgrim and Cerhan, {James R.} and Chanock, {Stephen J.} and Nathaniel Rothman and Slager, {Susan L.}",

note = "Funding Information: We thank C. Allmer, E. Angelucci, A. Bigelow, I. Brock, K. Butterbach, A. Chabrier, D. Chan-Lam, J.M. Conners, D. Connley, M. Cornelis, K. Corsano, C. Dalley, D. Cox, H. Cramp, R. Cutting, H. Dykes, L. Ershler, A. Gabbas, R.P. Gallagher, R.D. Gascoyne, P. Hui, L. Irish, L. Jacobus, S. Kaul, J. Lunde, M. McAdams, R. Montalvan, M. Rais, T. Rattle, L. Rigacci, K. Snyder, G. Specchia, M. Stagner, P. Taylor, G. Thomas, C. Tornow, G. Wood, M. Yang and M. Zucca for their assistance. The overall GWAS project was supported by the intramural program of the Division of Cancer Epidemiology and Genetics, NCI, US National Institutes of Health. A full list of acknowledgments is provided in the Supplementary Note.",

year = "2013",

month = aug,

doi = "10.1038/ng.2652",

language = "English",

volume = "45",

pages = "868--876",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "8",

}

Berndt, SI, Skibola, CF, Joseph, V, Camp, NJ, Nieters, A, Wang, Z, Cozen, W, Monnereau, A, Wang, SS, Kelly, RS, Lan, Q, Teras, LR, Chatterjee, N, Chung, CC, Yeager, M, Brooks-Wilson, AR, Hartge, P, Purdue, MP, Birmann, BM, Armstrong, BK, Cocco, P, Zhang, Y, Severi, G, Zeleniuch-Jacquotte, A, Lawrence, C, Burdette, L, Yuenger, J, Hutchinson, A, Jacobs, KB, Call, TG, Shanafelt, TD, Novak, AJ, Kay, NE, Liebow, M, Wang, AH, Smedby, KE, Adami, HO, Melbye, M, Glimelius, B, Chang, ET, Glenn, M, Curtin, K, Cannon-Albright, LA, Jones, B, Diver, WR, Link, BK, Weiner, GJ, Conde, L, Bracci, PM, Riby, J, Holly, EA, Smith, MT, Jackson, RD, Tinker, LF, Benavente, Y, Becker, N, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, McKay, J, Staines, A, Rabe, KG, Achenbach, SJ, Vachon, CM, Goldin, LR, Strom, SS, Lanasa, MC, Spector, LG, Leis, JF, Cunningham, JM, Weinberg, JB, Morrison, VA, Caporaso, NE, Norman, AD, Linet, MS, De Roos, AJ, Morton, LM, Severson, RK, Riboli, E, Vineis, P, Kaaks, R, Trichopoulos, D, Masala, G, Weiderpass, E, Chirlaque, MD, Vermeulen, RCH, Travis, RC, Giles, GG, Albanes, D, Virtamo, J, Weinstein, S, Clavel, J, Zheng, T, Holford, TR, Offit, K, Zelenetz, A, Klein, RJ, Spinelli, JJ, Bertrand, KA, Laden, F, Giovannucci, E, Kraft, P, Kricker, A, Turner, J, Vajdic, CM, Ennas, MG, Ferri, GM, Miligi, L, Liang, L, Sampson, J, Crouch, S, Park, JH, North, KE, Cox, A, Snowden, JA, Wright, J, Carracedo, A, Lopez-Otin, C, Bea, S, Salaverria, I, Martin-Garcia, D, Campo, E, Fraumeni, JF, De Sanjose, S, Hjalgrim, H, Cerhan, JR, Chanock, SJ, Rothman, N & Slager, SL 2013, 'Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia', Nature Genetics, vol. 45, no. 8, pp. 868-876. https://doi.org/10.1038/ng.2652

TY - JOUR

T1 - Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

AU - Berndt, Sonja I.

AU - Skibola, Christine F.

AU - Joseph, Vijai

AU - Camp, Nicola J.

AU - Nieters, Alexandra

AU - Wang, Zhaoming

AU - Cozen, Wendy

AU - Monnereau, Alain

AU - Wang, Sophia S.

AU - Kelly, Rachel S.

AU - Lan, Qing

AU - Teras, Lauren R.

AU - Chatterjee, Nilanjan

AU - Chung, Charles C.

AU - Yeager, Meredith

AU - Brooks-Wilson, Angela R.

AU - Hartge, Patricia

AU - Purdue, Mark P.

AU - Birmann, Brenda M.

AU - Armstrong, Bruce K.

AU - Cocco, Pierluigi

AU - Zhang, Yawei

AU - Severi, Gianluca

AU - Zeleniuch-Jacquotte, Anne

AU - Lawrence, Charles

AU - Burdette, Laurie

AU - Yuenger, Jeffrey

AU - Hutchinson, Amy

AU - Jacobs, Kevin B.

AU - Call, Timothy G.

AU - Shanafelt, Tait D.

AU - Novak, Anne J.

AU - Kay, Neil E.

AU - Liebow, Mark

AU - Wang, Alice H.

AU - Smedby, Karin E.

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 - Jones, Brandt

AU - Diver, W. Ryan

AU - Link, Brian K.

AU - Weiner, George J.

AU - Conde, Lucia

AU - Bracci, Paige M.

AU - Riby, Jacques

AU - Holly, Elizabeth A.

AU - Smith, Martyn T.

AU - Jackson, Rebecca D.

AU - Tinker, Lesley F.

AU - Benavente, Yolanda

AU - Becker, Nikolaus

AU - Boffetta, Paolo

AU - Brennan, Paul

AU - Foretova, Lenka

AU - Maynadie, Marc

AU - McKay, James

AU - Staines, Anthony

AU - Rabe, Kari G.

AU - Achenbach, Sara J.

AU - Vachon, Celine M.

AU - Goldin, Lynn R.

AU - Strom, Sara S.

AU - Lanasa, Mark C.

AU - Spector, Logan G.

AU - Leis, Jose F.

AU - Cunningham, Julie M.

AU - Weinberg, J. Brice

AU - Morrison, Vicki A.

AU - Caporaso, Neil E.

AU - Norman, Aaron D.

AU - Linet, Martha S.

AU - De Roos, Anneclaire J.

AU - Morton, Lindsay M.

AU - Severson, Richard K.

AU - Riboli, Elio

AU - Vineis, Paolo

AU - Kaaks, Rudolph

AU - Trichopoulos, Dimitrios

AU - Masala, Giovanna

AU - Weiderpass, Elisabete

AU - Chirlaque, María Dolores

AU - Vermeulen, Roel C.H.

AU - Travis, Ruth C.

AU - Giles, Graham G.

AU - Albanes, Demetrius

AU - Virtamo, Jarmo

AU - Weinstein, Stephanie

AU - Clavel, Jacqueline

AU - Zheng, Tongzhang

AU - Holford, Theodore R.

AU - Offit, Kenneth

AU - Zelenetz, Andrew

AU - Klein, Robert J.

AU - Spinelli, John J.

AU - Bertrand, Kimberly A.

AU - Laden, Francine

AU - Giovannucci, Edward

AU - Kraft, Peter

AU - Kricker, Anne

AU - Turner, Jenny

AU - Vajdic, Claire M.

AU - Ennas, Maria Grazia

AU - Ferri, Giovanni M.

AU - Miligi, Lucia

AU - Liang, Liming

AU - Sampson, Joshua

AU - Crouch, Simon

AU - Park, Ju Hyun

AU - North, Kari E.

AU - Cox, Angela

AU - Snowden, John A.

AU - Wright, Josh

AU - Carracedo, Angel

AU - Lopez-Otin, Carlos

AU - Bea, Silvia

AU - Salaverria, Itziar

AU - Martin-Garcia, David

AU - Campo, Elias

AU - Fraumeni, Joseph F.

AU - De Sanjose, Silvia

AU - Hjalgrim, Henrik

AU - Cerhan, James R.

AU - Chanock, Stephen J.

AU - Rothman, Nathaniel

AU - Slager, Susan L.

N1 - Funding Information: We thank C. Allmer, E. Angelucci, A. Bigelow, I. Brock, K. Butterbach, A. Chabrier, D. Chan-Lam, J.M. Conners, D. Connley, M. Cornelis, K. Corsano, C. Dalley, D. Cox, H. Cramp, R. Cutting, H. Dykes, L. Ershler, A. Gabbas, R.P. Gallagher, R.D. Gascoyne, P. Hui, L. Irish, L. Jacobus, S. Kaul, J. Lunde, M. McAdams, R. Montalvan, M. Rais, T. Rattle, L. Rigacci, K. Snyder, G. Specchia, M. Stagner, P. Taylor, G. Thomas, C. Tornow, G. Wood, M. Yang and M. Zucca for their assistance. The overall GWAS project was supported by the intramural program of the Division of Cancer Epidemiology and Genetics, NCI, US National Institutes of Health. A full list of acknowledgments is provided in the Supplementary Note.

PY - 2013/8

Y1 - 2013/8

N2 - Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10-14), 18q21.33 (BCL2, P = 7.76 × 10-11), 11p15.5 (C11orf21, P = 2.15 × 10 -10), 4q25 (LEF1, P = 4.24 × 10-10), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 × 10-9), 9p21.3 (CDKN2B-AS1, P = 1.27 × 10-8), 18q21.32 (PMAIP1, P = 2.51 × 10 -8), 15q15.1 (BMF, P = 2.71 × 10-10) and 2p22.2 (QPCT, P = 1.68 × 10-8), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 × 10-18). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 × 10-8) and 5p15.33 (TERT, P = 1.92 × 10-7). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.

AB - Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10-14), 18q21.33 (BCL2, P = 7.76 × 10-11), 11p15.5 (C11orf21, P = 2.15 × 10 -10), 4q25 (LEF1, P = 4.24 × 10-10), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 × 10-9), 9p21.3 (CDKN2B-AS1, P = 1.27 × 10-8), 18q21.32 (PMAIP1, P = 2.51 × 10 -8), 15q15.1 (BMF, P = 2.71 × 10-10) and 2p22.2 (QPCT, P = 1.68 × 10-8), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 × 10-18). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 × 10-8) and 5p15.33 (TERT, P = 1.92 × 10-7). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.

UR - http://www.scopus.com/inward/record.url?scp=84881023533&partnerID=8YFLogxK

U2 - 10.1038/ng.2652

DO - 10.1038/ng.2652

M3 - Article

C2 - 23770605

AN - SCOPUS:84881023533

SN - 1061-4036

VL - 45

SP - 868

EP - 876

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -

Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

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Bibliographical note

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