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

SI Berndt; CF Skibola; V Joseph; NJ Camp; A Nieters; Z Wang; W Cozen; A Monnereau; SS Wang; RS Kelly; Q Lan; LR Teras; N Chatterjee; CC Chung; M Yeager; AR Brooks-Wilson; P Hartge; MP Purdue; BM  Birmann; BK Armstrong; P Cocco; Y Zhang; G Severi; A Zeleniuch-Jacquotte; C Lawrence; L Burdette; J Yuenger; A Hutchinson; KB Jacobs; TG Call; TD Shanafelt; AJ Novak; NE Kay; M Liebow; AH Wang; KE Smedby; HO Adami; M Melbye; B Glimelius; ET Chang; M Glenn; K Curtin; LA Cannon-Albright; B Jones; WR Diver; BK Link; GJ Weiner; L Conde; PM  Bracci; J Riby; EA Holly; MT Smith; RD Jackson; LF Tinker; Y Benavente; N Becker; P Boffetta; P Brennan; L Foretova; M Maynadie; J McKay; A Staines; KG Rabe; SJ Achenbach; CM Vachon; LR Goldin; SS Strom; MC Lanasa; LG Spector; JF Leis; JM Cunningham; JB Weinberg; VA Morrison; NE Caporaso; AD Norman; MS Linet; AJ De Roos; LM Morton; RK Severson; E Riboli; P Vineis; R Kaaks; D Trichopoulos; G Masala; E Weiderpass; MD Chirlaque; RC Vermeulen; RC Travis; GG Giles; D Albanes; J Virtamo; S Weinstein; J Clavel; T Zheng; TR Holford; K Offit; A Zelenetz; RJ Klein; JJ Spinelli; KA Bertrand; F Laden; E Giovannucci; P Kraft; A Kricker; J Turner; CM Vajdic; MG Ennas; GM Ferri; L Miligi; L Liang; J Sampson; Simon Crouch; JH Park; KE North; A Cox; JA Snowden; J Wright; A Carracedo; C Lopez-Otin; S Bea; I Salaverria; D Martin-Garcia; E Campo; JF Fraumeni Jr; S de Sanjose; H Hjalgrim; JR Cerhan; SJ Chanock; N Rothman; SL Slager

doi:10.1038/ng.2652

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

SI Berndt, CF Skibola, V Joseph, NJ Camp, A Nieters, Z Wang, W Cozen, A Monnereau, SS Wang, RS Kelly, Q Lan, LR Teras, N Chatterjee, CC Chung, M Yeager, AR Brooks-Wilson, P Hartge, MP Purdue, BM Birmann, BK ArmstrongP Cocco, Y Zhang, G Severi, A Zeleniuch-Jacquotte , C Lawrence, L Burdette, J Yuenger, A Hutchinson, KB Jacobs, TG Call, TD Shanafelt , AJ Novak, NE Kay, M Liebow, AH Wang, KE Smedby, HO Adami, M Melbye, B Glimelius, ET Chang, M Glenn, K Curtin, LA Cannon-Albright , B Jones, WR Diver, BK Link, GJ Weiner, L Conde, PM Bracci, J Riby, EA Holly, MT Smith, RD Jackson, LF Tinker, Y Benavente, N Becker, P Boffetta, P Brennan, L Foretova, M Maynadie, J McKay, A Staines, KG Rabe, SJ Achenbach, CM Vachon, LR Goldin, SS Strom, MC Lanasa, LG Spector, JF Leis, JM Cunningham, JB Weinberg, VA Morrison, NE Caporaso, AD Norman, MS Linet, AJ De Roos, LM Morton, RK Severson, E Riboli, P Vineis, R Kaaks, D Trichopoulos, G Masala, E Weiderpass, MD Chirlaque, RC Vermeulen, RC Travis, GG Giles, D Albanes, J Virtamo, S Weinstein, J Clavel, T Zheng, TR Holford, K Offit, A Zelenetz, RJ Klein, JJ Spinelli, KA Bertrand, F Laden, E Giovannucci , P Kraft, A Kricker, J Turner, CM Vajdic, MG Ennas, GM Ferri, L Miligi, L Liang, J Sampson, Simon Crouch, JH Park, KE North, A Cox, JA Snowden, J Wright, A Carracedo, C Lopez-Otin, S Bea, I Salaverria, D Martin-Garcia, E Campo, JF Fraumeni Jr, S de Sanjose, H Hjalgrim, JR Cerhan, SJ Chanock, N Rothman, SL Slager

Health Sciences

Research output: Contribution to journal › Article › 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 = 1.22 × 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
Journal	Nature genetics
Volume	45
Issue number	8
Early online date	16 Jun 2013
DOIs	https://doi.org/10.1038/ng.2652
Publication status	Published - Aug 2013

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10.1038/ng.2652

http://www.nature.com/ng/journal/v45/n8/full/ng.2652.html

Cite this

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., ... Slager, SL. (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{8d2af43ab2794519ac310c11d514b3d0,

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 = "SI Berndt and CF Skibola and V Joseph and NJ Camp and A Nieters and Z Wang and W Cozen and A Monnereau and SS Wang and RS Kelly and Q Lan and LR Teras and N Chatterjee and CC Chung and M Yeager and AR Brooks-Wilson and P Hartge and MP Purdue and BM Birmann and BK 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 KB Jacobs and TG Call and TD Shanafelt and AJ Novak and NE Kay and M Liebow and AH Wang and KE Smedby and HO Adami and M Melbye and B Glimelius and ET Chang and M Glenn and K Curtin and LA Cannon-Albright and B Jones and WR Diver and BK Link and GJ Weiner and L Conde and PM Bracci and J Riby and EA Holly and MT Smith and RD Jackson and LF 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 KG Rabe and SJ Achenbach and CM Vachon and LR Goldin and SS Strom and MC Lanasa and LG Spector and JF Leis and JM Cunningham and JB Weinberg and VA Morrison and NE Caporaso and AD Norman and MS Linet and {De Roos}, AJ and LM Morton and RK Severson and E Riboli and P Vineis and R Kaaks and D Trichopoulos and G Masala and E Weiderpass and MD Chirlaque and RC Vermeulen and RC Travis and GG Giles and D Albanes and J Virtamo and S Weinstein and J Clavel and T Zheng and TR Holford and K Offit and A Zelenetz and RJ Klein and JJ Spinelli and KA Bertrand and F Laden and E Giovannucci and P Kraft and A Kricker and J Turner and CM Vajdic and MG Ennas and GM Ferri and L Miligi and L Liang and J Sampson and Simon Crouch and JH Park and KE North and A Cox and JA 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 {Fraumeni Jr}, JF and {de Sanjose}, S and H Hjalgrim and JR Cerhan and SJ Chanock and N Rothman and SL Slager",

year = "2013",

month = aug,

doi = "10.1038/ng.2652",

language = "English",

volume = "45",

pages = "868--876",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

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, RC, 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 Jr, 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, SI

AU - Skibola, CF

AU - Joseph, V

AU - Camp, NJ

AU - Nieters, A

AU - Wang, Z

AU - Cozen, W

AU - Monnereau, A

AU - Wang, SS

AU - Kelly, RS

AU - Lan, Q

AU - Teras, LR

AU - Chatterjee, N

AU - Chung, CC

AU - Yeager, M

AU - Brooks-Wilson, AR

AU - Hartge, P

AU - Purdue, MP

AU - Birmann, BM

AU - Armstrong, BK

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, KB

AU - Call, TG

AU - Shanafelt , TD

AU - Novak, AJ

AU - Kay, NE

AU - Liebow, M

AU - Wang, AH

AU - Smedby, KE

AU - Adami, HO

AU - Melbye, M

AU - Glimelius, B

AU - Chang, ET

AU - Glenn, M

AU - Curtin, K

AU - Cannon-Albright , LA

AU - Jones, B

AU - Diver, WR

AU - Link, BK

AU - Weiner, GJ

AU - Conde, L

AU - Bracci, PM

AU - Riby, J

AU - Holly, EA

AU - Smith, MT

AU - Jackson, RD

AU - Tinker, LF

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, KG

AU - Achenbach, SJ

AU - Vachon, CM

AU - Goldin, LR

AU - Strom, SS

AU - Lanasa, MC

AU - Spector, LG

AU - Leis, JF

AU - Cunningham, JM

AU - Weinberg, JB

AU - Morrison, VA

AU - Caporaso, NE

AU - Norman, AD

AU - Linet, MS

AU - De Roos, AJ

AU - Morton, LM

AU - Severson, RK

AU - Riboli, E

AU - Vineis, P

AU - Kaaks, R

AU - Trichopoulos, D

AU - Masala, G

AU - Weiderpass, E

AU - Chirlaque, MD

AU - Vermeulen, RC

AU - Travis, RC

AU - Giles, GG

AU - Albanes, D

AU - Virtamo, J

AU - Weinstein, S

AU - Clavel, J

AU - Zheng, T

AU - Holford, TR

AU - Offit, K

AU - Zelenetz, A

AU - Klein, RJ

AU - Spinelli, JJ

AU - Bertrand, KA

AU - Laden, F

AU - Giovannucci , E

AU - Kraft, P

AU - Kricker, A

AU - Turner, J

AU - Vajdic, CM

AU - Ennas, MG

AU - Ferri, GM

AU - Miligi, L

AU - Liang, L

AU - Sampson, J

AU - Crouch, Simon

AU - Park, JH

AU - North, KE

AU - Cox, A

AU - Snowden, JA

AU - Wright, J

AU - Carracedo, A

AU - Lopez-Otin, C

AU - Bea, S

AU - Salaverria, I

AU - Martin-Garcia, D

AU - Campo, E

AU - Fraumeni Jr, JF

AU - de Sanjose, S

AU - Hjalgrim, H

AU - Cerhan, JR

AU - Chanock, SJ

AU - Rothman, N

AU - Slager, SL

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.

U2 - 10.1038/ng.2652

DO - 10.1038/ng.2652

M3 - Article

VL - 45

SP - 868

EP - 876

JO - Nature genetics

JF - Nature genetics

SN - 1061-4036

IS - 8

ER -