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Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

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Publication date

2016

Authors

Berndt, Sonja I
Camp, Nicola J
Skibola, Christine F
Vijai, Joseph
Wang, Zhaoming
Gu, Jian
Nieters, Alexandra
Kelly, Rachel S
Smedby, Karin E
Monnereau, Alain

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DOI

https://doi.org/10.1038/ncomms10933

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Article

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Abstract

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10(-11)), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10(-8)) and 3q28 (rs9815073, LPP, P=3.62 × 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10(-11)) in the combined analysis. We find suggestive evidence (P<5 × 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.

Keywords

Adaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Membrane Proteins, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins, Serpins, T-Box Domain Proteins

Citation

Berndt, S I, Camp, N J, Skibola, C F, Vijai, J, Wang, Z, Gu, J, Nieters, A, Kelly, R S, Smedby, K E, Monnereau, A, Cozen, W, Cox, A, Wang, S S, Lan, Q, Teras, L R, Machado, M, Yeager, M, Brooks-Wilson, A R, Hartge, P, Purdue, M P, Birmann, B M, Vajdic, C M, Cocco, P, Zhang, Y, Giles, G G, Zeleniuch-Jacquotte, A, Lawrence, C, Montalvan, R, Burdett, L, Hutchinson, A, Ye, Y, Call, T G, Shanafelt, T D, Novak, A J, Kay, N E, Liebow, M, Cunningham, J M, Allmer, C, Hjalgrim, H, Adami, H-O, Melbye, M, Glimelius, B, Chang, E T, Glenn, M, Curtin, K, Cannon-Albright, L A, Diver, W R, Link, B K, Weiner, G J, Conde, L, Bracci, P M, Riby, J, Arnett, D K, Zhi, D, Leach, J M, Holly, E A, Jackson, R D, Tinker, L F, Benavente, Y, Sala, N, Casabonne, D, Becker, N, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, McKay, J, Staines, A, Chaffee, K G, Achenbach, S J, Vachon, C M, Goldin, L R, Strom, S S, Leis, J F, Weinberg, J B, Caporaso, N E, Norman, A D, De Roos, A J, Morton, L M, Severson, R K, Riboli, E, Vineis, P, Kaaks, R, Masala, G, Weiderpass, E, Chirlaque, M-D, Vermeulen, R C H, Travis, R C, Southey, M C, Milne, R L, Albanes, D, Virtamo, J, Weinstein, S, Clavel, J, Zheng, T, Holford, T R, Villano, D J, Maria, A, Spinelli, J J, Gascoyne, R D, Connors, J M, Bertrand, K A, Giovannucci, E, Kraft, P, Kricker, A, Turner, J, Ennas, M G, Ferri, G M, Miligi, L, Liang, L, Ma, B, Huang, J, Crouch, S, Park, J-H, Chatterjee, N, North, K E, Snowden, J A, Wright, J, Fraumeni, J F, Offit, K, Wu, X, de Sanjose, S, Cerhan, J R, Chanock, S J, Rothman, N & Slager, S L 2016, 'Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia', Nature Communications [E], vol. 7, 10933. https://doi.org/10.1038/ncomms10933

URI

https://dspace.library.uu.nl/handle/1874/345512