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

Publication ,  Journal Article
Berndt, SI; Skibola, CF; Joseph, V; Camp, NJ; Nieters, A; Wang, Z; Cozen, W; Monnereau, A; Wang, SS; Kelly, RS; Lan, Q; Teras, LR; Chung, CC ...
Published in: Nat Genet
August 2013
Published version (DOI) Link to item

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.

Duke Scholars

Joe Brice Weinberg
Author Joe Brice Weinberg Medicine, Hematology
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Published In

Nat Genet

DOI

10.1038/ng.2652

EISSN

1546-1718

Publication Date

August 2013

Volume

45

Issue

8

Start / End Page

868 / 876

Location

United States

Related Subject Headings

  • Risk
  • Recombination, Genetic
  • Polymorphism, Single Nucleotide
  • Linkage Disequilibrium
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Loci
  • Developmental Biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Berndt, S. I., Skibola, C. F., Joseph, V., Camp, N. J., Nieters, A., Wang, Z., … Slager, S. L. (2013). Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia. Nat Genet, 45(8), 868–876. https://doi.org/10.1038/ng.2652
Berndt, Sonja I., Christine F. Skibola, Vijai Joseph, Nicola J. Camp, Alexandra Nieters, Zhaoming Wang, Wendy Cozen, et al. “Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia.” Nat Genet 45, no. 8 (August 2013): 868–76. https://doi.org/10.1038/ng.2652.
Berndt SI, Skibola CF, Joseph V, Camp NJ, Nieters A, Wang Z, et al. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia. Nat Genet. 2013 Aug;45(8):868–76.
Berndt, Sonja I., et al. “Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia.” Nat Genet, vol. 45, no. 8, Aug. 2013, pp. 868–76. Pubmed, doi:10.1038/ng.2652.
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 H-O, 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 M-D, 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 J-H, 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. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia. Nat Genet. 2013 Aug;45(8):868–876.

Published In

Nat Genet

DOI

10.1038/ng.2652

EISSN

1546-1718

Publication Date

August 2013

Volume

45

Issue

8

Start / End Page

868 / 876

Location

United States

Related Subject Headings

  • Risk
  • Recombination, Genetic
  • Polymorphism, Single Nucleotide
  • Linkage Disequilibrium
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Loci
  • Developmental Biology