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

S.I. Berndt; C.F. Skibola; V. Joseph; N.J. Camp; A. Nieters; Z. Wang; W. Cozen; A. Monnereau; S.S. Wang; R.S. Kelly; Q. Lan; L.R. Teras; N. Chatterjee; C.C. Chung; M. Yeager; A.R. Brooks-Wilson; P. Hartge; M.P. Purdue; B.M. Birmann; B.K. Armstrong; P. Cocco; Y. Zhang; G. Severi; A. Zeleniuch-Jacquotte; C. Lawrence; L. Burdette; J. Yuenger; A. Hutchinson; K.B. Jacobs; T.G. Call; T.D. Shanafelt; A.J. Novak; N.E. Kay; M. Liebow; A.H. Wang; K.E. Smedby; H.O. Adami; M. Melbye; B Glimelius; E.T. Chang; M. Glenn; K. Curtin; L.A. Cannon-Albright; B. Jones; W.R. Diver; B.K. Link; G.J. Weiner; L. Conde; P.M. Bracci; J. Riby; E.A. Holly; M.T. Smith; R.D. Jackson; L.F. Tinker; Y. Benavente; N. Becker; P. Boffetta; P. Brennan; L. Foretova; M. Maynadie; J. McKay; A. Staines; K.G. Rabe; S.J. Achenbach; C.M. Vachon; L.R. Goldin; S.S. Strom; M.C. Lanasa; L.G. Spector; J.F. Leis; J.M. Cunningham; J.B. Weinberg; V.A. Morrison; N.E. Caporaso; A.D. Norman; M.S. Linet; A.J. de Roos; L.M. Morton; R.K. Severson; E. Riboli; P. Vineis; R. Kaaks; D. Trichopoulos; G. Masala; E. Weiderpass; M.D. Chirlaque; R.C.H. Vermeulen; R.C. Travis; G.G. Giles; D. Albanes; J. Virtamo; S. Weinstein; J. Clavel; T. Zheng; T.R. Holford; K. Offit; A. Zelenetz; R.J.T. Klein; J.J. Spinelli; K.A. Bertrand; F. Laden; E. Giovannucci; P. Kraft; A. Kricker; J. Turner; C.M. Vajdic; M.G. Ennas; G.M. Ferri; L. Miligi; L. Liang; J. Sampson; S. Crouch; J.H. Park; K.E. North; A. Cox; J.A. Snowden; J. Wright; A. Carracedo; C. Lopez-Otin; S. Bea; I. Salaverria; D. Martin-Garcia; E. Campo; J.r. F raumeni JF; S. de Sanjose; H. Hjalgrim; J.R. Cerhan; S.J. Chanock; N. Rothman; S.L. Slager

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

S.I. Berndt, C.F. Skibola, V. Joseph, N.J. Camp, A. Nieters, Z. Wang, W. Cozen, A. Monnereau, S.S. Wang, R.S. Kelly, Q. Lan, L.R. Teras, N. Chatterjee, C.C. Chung, M. Yeager, A.R. Brooks-Wilson, P. Hartge, M.P. Purdue, B.M. Birmann, B.K. ArmstrongP. Cocco, Y. Zhang, G. Severi, A. Zeleniuch-Jacquotte, C. Lawrence, L. Burdette, J. Yuenger, A. Hutchinson, K.B. Jacobs, T.G. Call, T.D. Shanafelt, A.J. Novak, N.E. Kay, M. Liebow, A.H. Wang, K.E. Smedby, H.O. Adami, M. Melbye, B Glimelius, E.T. Chang, M. Glenn, K. Curtin, L.A. Cannon-Albright, B. Jones, W.R. Diver, B.K. Link, G.J. Weiner, L. Conde, P.M. Bracci, J. Riby, E.A. Holly, M.T. Smith, R.D. Jackson, L.F. Tinker, Y. Benavente, N. Becker, P. Boffetta, P. Brennan, L. Foretova, M. Maynadie, J. McKay, A. Staines, K.G. Rabe, S.J. Achenbach, C.M. Vachon, L.R. Goldin, S.S. Strom, M.C. Lanasa, L.G. Spector, J.F. Leis, J.M. Cunningham, J.B. Weinberg, V.A. Morrison, N.E. Caporaso, A.D. Norman, M.S. Linet, A.J. de Roos, L.M. Morton, R.K. Severson, E. Riboli, P. Vineis, R. Kaaks, D. Trichopoulos, G. Masala, E. Weiderpass, M.D. Chirlaque, R.C.H. Vermeulen, R.C. Travis, G.G. Giles, D. Albanes, J. Virtamo, S. Weinstein, J. Clavel, T. Zheng, T.R. Holford, K. Offit, A. Zelenetz, R.J.T. Klein, J.J. Spinelli, K.A. Bertrand, F. Laden, E. Giovannucci, P. Kraft, A. Kricker, J. Turner, C.M. Vajdic, M.G. Ennas, G.M. Ferri, L. Miligi, L. Liang, J. Sampson, S. Crouch, J.H. Park, K.E. North, A. Cox, J.A. Snowden, J. Wright, A. Carracedo, C. Lopez-Otin, S. Bea, I. Salaverria, D. Martin-Garcia, E. Campo, J.r. F raumeni JF, S. de Sanjose, H. Hjalgrim, J.R. Cerhan, S.J. Chanock, N. Rothman, S.L. Slager

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

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=1.22x10(-14)), 18q21.33 (BCL2, P=7.76x10(-11)), 11p15.5 (C11orf21, P=2.15x10(-10)), 4q25 (LEF1, P=4.24x10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P=2.50x10(-9)), 9p21.3 (CDKN2B-AS1, P=1.27x10(-8)), 18q21.32 (PMAIP1, P=2.51x10(-8)), 15q15.1 (BMF, P=2.71x10(-10)) and 2p22.2 (QPCT, P=1.68x10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P=2.08x10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P=5.40x10(-8)) and 5p15.33 (TERT, P=1.92x10(-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	Undefined/Unknown
Pages (from-to)	868-76
Number of pages	9
Journal	Nature Genetics
Volume	45
Issue number	8
Publication status	Published - 2013

Cite this

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), 868-76.

@article{613e36f633134e8fb4e96362f74e4f10,

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=1.22x10(-14)), 18q21.33 (BCL2, P=7.76x10(-11)), 11p15.5 (C11orf21, P=2.15x10(-10)), 4q25 (LEF1, P=4.24x10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P=2.50x10(-9)), 9p21.3 (CDKN2B-AS1, P=1.27x10(-8)), 18q21.32 (PMAIP1, P=2.51x10(-8)), 15q15.1 (BMF, P=2.71x10(-10)) and 2p22.2 (QPCT, P=1.68x10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P=2.08x10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P=5.40x10(-8)) and 5p15.33 (TERT, P=1.92x10(-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 = "S.I. Berndt and C.F. Skibola and V. Joseph and N.J. Camp and A. Nieters and Z. Wang and W. Cozen and A. Monnereau and S.S. Wang and R.S. Kelly and Q. Lan and L.R. Teras and N. Chatterjee and C.C. Chung and M. Yeager and A.R. Brooks-Wilson and P. Hartge and M.P. Purdue and B.M. Birmann and B.K. Armstrong and P. Cocco and Y. Zhang and G. Severi and A. Zeleniuch-Jacquotte and C. Lawrence and L. Burdette and J. Yuenger and A. Hutchinson and K.B. Jacobs and T.G. Call and T.D. Shanafelt and A.J. Novak and N.E. Kay and M. Liebow and A.H. Wang and K.E. Smedby and H.O. Adami and M. Melbye and B Glimelius and E.T. Chang and M. Glenn and K. Curtin and L.A. Cannon-Albright and B. Jones and W.R. Diver and B.K. Link and G.J. Weiner and L. Conde and P.M. Bracci and J. Riby and E.A. Holly and M.T. Smith and R.D. Jackson and L.F. Tinker and Y. Benavente and N. Becker and P. Boffetta and P. Brennan and L. Foretova and M. Maynadie and J. McKay and A. Staines and K.G. Rabe and S.J. Achenbach and C.M. Vachon and L.R. Goldin and S.S. Strom and M.C. Lanasa and L.G. Spector and J.F. Leis and J.M. Cunningham and J.B. Weinberg and V.A. Morrison and N.E. Caporaso and A.D. Norman and M.S. Linet and {de Roos}, A.J. and L.M. Morton and R.K. Severson and E. Riboli and P. Vineis and R. Kaaks and D. Trichopoulos and G. Masala and E. Weiderpass and M.D. Chirlaque and R.C.H. Vermeulen and R.C. Travis and G.G. Giles and D. Albanes and J. Virtamo and S. Weinstein and J. Clavel and T. Zheng and T.R. Holford and K. Offit and A. Zelenetz and R.J.T. Klein and J.J. Spinelli and K.A. Bertrand and F. Laden and E. Giovannucci and P. Kraft and A. Kricker and J. Turner and C.M. Vajdic and M.G. Ennas and G.M. Ferri and L. Miligi and L. Liang and J. Sampson and S. Crouch and J.H. Park and K.E. North and A. Cox and J.A. Snowden and J. Wright and A. Carracedo and C. Lopez-Otin and S. Bea and I. Salaverria and D. Martin-Garcia and E. Campo and {F raumeni JF}, J.r. and {de Sanjose}, S. and H. Hjalgrim and J.R. Cerhan and S.J. Chanock and N. Rothman and S.L. Slager",

year = "2013",

language = "Undefined/Unknown",

volume = "45",

pages = "868--76",

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, RJT, 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, F raumeni JF, JR, 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. 868-76.

TY - JOUR

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

AU - Berndt, S.I.

AU - Skibola, C.F.

AU - Joseph, V.

AU - Camp, N.J.

AU - Nieters, A.

AU - Wang, Z.

AU - Cozen, W.

AU - Monnereau, A.

AU - Wang, S.S.

AU - Kelly, R.S.

AU - Lan, Q.

AU - Teras, L.R.

AU - Chatterjee, N.

AU - Chung, C.C.

AU - Yeager, M.

AU - Brooks-Wilson, A.R.

AU - Hartge, P.

AU - Purdue, M.P.

AU - Birmann, B.M.

AU - Armstrong, B.K.

AU - Cocco, P.

AU - Zhang, Y.

AU - Severi, G.

AU - Zeleniuch-Jacquotte, A.

AU - Lawrence, C.

AU - Burdette, L.

AU - Yuenger, J.

AU - Hutchinson, A.

AU - Jacobs, K.B.

AU - Call, T.G.

AU - Shanafelt, T.D.

AU - Novak, A.J.

AU - Kay, N.E.

AU - Liebow, M.

AU - Wang, A.H.

AU - Smedby, K.E.

AU - Adami, H.O.

AU - Melbye, M.

AU - Glimelius, B

AU - Chang, E.T.

AU - Glenn, M.

AU - Curtin, K.

AU - Cannon-Albright, L.A.

AU - Jones, B.

AU - Diver, W.R.

AU - Link, B.K.

AU - Weiner, G.J.

AU - Conde, L.

AU - Bracci, P.M.

AU - Riby, J.

AU - Holly, E.A.

AU - Smith, M.T.

AU - Jackson, R.D.

AU - Tinker, L.F.

AU - Benavente, Y.

AU - Becker, N.

AU - Boffetta, P.

AU - Brennan, P.

AU - Foretova, L.

AU - Maynadie, M.

AU - McKay, J.

AU - Staines, A.

AU - Rabe, K.G.

AU - Achenbach, S.J.

AU - Vachon, C.M.

AU - Goldin, L.R.

AU - Strom, S.S.

AU - Lanasa, M.C.

AU - Spector, L.G.

AU - Leis, J.F.

AU - Cunningham, J.M.

AU - Weinberg, J.B.

AU - Morrison, V.A.

AU - Caporaso, N.E.

AU - Norman, A.D.

AU - Linet, M.S.

AU - de Roos, A.J.

AU - Morton, L.M.

AU - Severson, R.K.

AU - Riboli, E.

AU - Vineis, P.

AU - Kaaks, R.

AU - Trichopoulos, D.

AU - Masala, G.

AU - Weiderpass, E.

AU - Chirlaque, M.D.

AU - Vermeulen, R.C.H.

AU - Travis, R.C.

AU - Giles, G.G.

AU - Albanes, D.

AU - Virtamo, J.

AU - Weinstein, S.

AU - Clavel, J.

AU - Zheng, T.

AU - Holford, T.R.

AU - Offit, K.

AU - Zelenetz, A.

AU - Klein, R.J.T.

AU - Spinelli, J.J.

AU - Bertrand, K.A.

AU - Laden, F.

AU - Giovannucci, E.

AU - Kraft, P.

AU - Kricker, A.

AU - Turner, J.

AU - Vajdic, C.M.

AU - Ennas, M.G.

AU - Ferri, G.M.

AU - Miligi, L.

AU - Liang, L.

AU - Sampson, J.

AU - Crouch, S.

AU - Park, J.H.

AU - North, K.E.

AU - Cox, A.

AU - Snowden, J.A.

AU - Wright, J.

AU - Carracedo, A.

AU - Lopez-Otin, C.

AU - Bea, S.

AU - Salaverria, I.

AU - Martin-Garcia, D.

AU - Campo, E.

AU - F raumeni JF, J.r.

AU - de Sanjose, S.

AU - Hjalgrim, H.

AU - Cerhan, J.R.

AU - Chanock, S.J.

AU - Rothman, N.

AU - Slager, S.L.

PY - 2013

Y1 - 2013

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=1.22x10(-14)), 18q21.33 (BCL2, P=7.76x10(-11)), 11p15.5 (C11orf21, P=2.15x10(-10)), 4q25 (LEF1, P=4.24x10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P=2.50x10(-9)), 9p21.3 (CDKN2B-AS1, P=1.27x10(-8)), 18q21.32 (PMAIP1, P=2.51x10(-8)), 15q15.1 (BMF, P=2.71x10(-10)) and 2p22.2 (QPCT, P=1.68x10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P=2.08x10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P=5.40x10(-8)) and 5p15.33 (TERT, P=1.92x10(-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=1.22x10(-14)), 18q21.33 (BCL2, P=7.76x10(-11)), 11p15.5 (C11orf21, P=2.15x10(-10)), 4q25 (LEF1, P=4.24x10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P=2.50x10(-9)), 9p21.3 (CDKN2B-AS1, P=1.27x10(-8)), 18q21.32 (PMAIP1, P=2.51x10(-8)), 15q15.1 (BMF, P=2.71x10(-10)) and 2p22.2 (QPCT, P=1.68x10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P=2.08x10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P=5.40x10(-8)) and 5p15.33 (TERT, P=1.92x10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.

M3 - Article

SN - 1061-4036

VL - 45

SP - 868

EP - 876

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -