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

Publication ,  Journal Article
Berndt, SI; Camp, NJ; Skibola, CF; Vijai, J; Wang, Z; Gu, J; Nieters, A; Kelly, RS; Smedby, KE; Monnereau, A; Cozen, W; Cox, A; Wang, SS ...
Published in: Nat Commun
March 9, 2016

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

March 9, 2016

Volume

7

Start / End Page

10933

Location

England

Related Subject Headings

  • White People
  • T-Box Domain Proteins
  • Serpins
  • Proto-Oncogene Proteins
  • Polymorphism, Single Nucleotide
  • Membrane Proteins
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
 

Citation

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Berndt, S. I., Camp, N. J., Skibola, C. F., Vijai, J., Wang, Z., Gu, J., … Slager, S. L. (2016). Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia. Nat Commun, 7, 10933. https://doi.org/10.1038/ncomms10933
Berndt, Sonja I., Nicola J. Camp, Christine F. Skibola, Joseph Vijai, Zhaoming Wang, Jian Gu, Alexandra Nieters, et al. “Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia.Nat Commun 7 (March 9, 2016): 10933. https://doi.org/10.1038/ncomms10933.
Berndt SI, Camp NJ, Skibola CF, Vijai J, Wang Z, Gu J, et al. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia. Nat Commun. 2016 Mar 9;7:10933.
Berndt, Sonja I., et al. “Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia.Nat Commun, vol. 7, Mar. 2016, p. 10933. Pubmed, doi:10.1038/ncomms10933.
Berndt SI, Camp NJ, Skibola CF, Vijai J, Wang Z, Gu J, Nieters A, Kelly RS, Smedby KE, Monnereau A, Cozen W, Cox A, Wang SS, Lan Q, Teras LR, Machado M, Yeager M, Brooks-Wilson AR, Hartge P, Purdue MP, Birmann BM, Vajdic CM, Cocco P, Zhang Y, Giles GG, Zeleniuch-Jacquotte A, Lawrence C, Montalvan R, Burdett L, Hutchinson A, Ye Y, Call TG, Shanafelt TD, Novak AJ, Kay NE, Liebow M, Cunningham JM, Allmer C, Hjalgrim H, Adami H-O, Melbye M, Glimelius B, Chang ET, Glenn M, Curtin K, Cannon-Albright LA, Diver WR, Link BK, Weiner GJ, Conde L, Bracci PM, Riby J, Arnett DK, Zhi D, Leach JM, Holly EA, Jackson RD, Tinker LF, Benavente Y, Sala N, Casabonne D, Becker N, Boffetta P, Brennan P, Foretova L, Maynadie M, McKay J, Staines A, Chaffee KG, Achenbach SJ, Vachon CM, Goldin LR, Strom SS, Leis JF, Weinberg JB, Caporaso NE, Norman AD, De Roos AJ, Morton LM, Severson RK, Riboli E, Vineis P, Kaaks R, Masala G, Weiderpass E, Chirlaque M-D, Vermeulen RCH, Travis RC, Southey MC, Milne RL, Albanes D, Virtamo J, Weinstein S, Clavel J, Zheng T, Holford TR, Villano DJ, Maria A, Spinelli JJ, Gascoyne RD, Connors JM, Bertrand KA, Giovannucci E, Kraft P, Kricker A, Turner J, Ennas MG, Ferri GM, Miligi L, Liang L, Ma B, Huang J, Crouch S, Park J-H, Chatterjee N, North KE, Snowden JA, Wright J, Fraumeni JF, Offit K, Wu X, de Sanjose S, Cerhan JR, Chanock SJ, Rothman N, Slager SL. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia. Nat Commun. 2016 Mar 9;7:10933.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

March 9, 2016

Volume

7

Start / End Page

10933

Location

England

Related Subject Headings

  • White People
  • T-Box Domain Proteins
  • Serpins
  • Proto-Oncogene Proteins
  • Polymorphism, Single Nucleotide
  • Membrane Proteins
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease