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Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL.

Publication ,  Journal Article
Slager, SL; Rabe, KG; Achenbach, SJ; Vachon, CM; Goldin, LR; Strom, SS; Lanasa, MC; Spector, LG; Rassenti, LZ; Leis, JF; Camp, NJ; Glenn, M ...
Published in: Blood
February 10, 2011

Prior genome-wide association (GWA) studies have identified 10 susceptibility loci for risk of chronic lymphocytic leukemia (CLL). To identify additional loci, we performed a GWA study in 407 CLL cases (of which 102 had a family history of CLL) and 296 controls. Moreover, given the strong familial risk of CLL, we further subset our GWA analysis to the CLL cases with a family history of CLL to identify loci specific to these familial CLL cases. Our top hits from these analyses were evaluated in an additional sample of 252 familial CLL cases and 965 controls. Using all available data, we identified and confirmed an independent association of 4 single-nucleotide polymorphisms (SNPs) that met genome-wide statistical significance within the IRF8 (interferon regulatory factor 8) gene (combined P values ≤ 3.37 × 10(-8)), located in the previously identified 16q24.1 locus. Subsetting to familial CLL cases, we identified and confirmed a new locus on chromosome 6p21.3 (combined P value = 6.92 × 10(-9)). This novel region harbors the HLA-DQA1 and HLA-DRB5 genes. Finally, we evaluated the 10 previously reported SNPs in the overall sample and replicated 8 of them. Our findings support the hypothesis that familial CLL cases have additional genetic variants not seen in sporadic CLL. Additional loci among familial CLL cases may be identified through larger studies.

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Published In

Blood

DOI

EISSN

1528-0020

Publication Date

February 10, 2011

Volume

117

Issue

6

Start / End Page

1911 / 1916

Location

United States

Related Subject Headings

  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Odds Ratio
  • Male
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Interferon Regulatory Factors
  • Immunology
  • Humans
  • HLA-DRB5 Chains
  • HLA-DR Antigens
 

Citation

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Slager, S. L., Rabe, K. G., Achenbach, S. J., Vachon, C. M., Goldin, L. R., Strom, S. S., … Cerhan, J. R. (2011). Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL. Blood, 117(6), 1911–1916. https://doi.org/10.1182/blood-2010-09-308205
Slager, Susan L., Kari G. Rabe, Sara J. Achenbach, Celine M. Vachon, Lynn R. Goldin, Sara S. Strom, Mark C. Lanasa, et al. “Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL.Blood 117, no. 6 (February 10, 2011): 1911–16. https://doi.org/10.1182/blood-2010-09-308205.
Slager SL, Rabe KG, Achenbach SJ, Vachon CM, Goldin LR, Strom SS, et al. Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL. Blood. 2011 Feb 10;117(6):1911–6.
Slager, Susan L., et al. “Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL.Blood, vol. 117, no. 6, Feb. 2011, pp. 1911–16. Pubmed, doi:10.1182/blood-2010-09-308205.
Slager SL, Rabe KG, Achenbach SJ, Vachon CM, Goldin LR, Strom SS, Lanasa MC, Spector LG, Rassenti LZ, Leis JF, Camp NJ, Glenn M, Kay NE, Cunningham JM, Hanson CA, Marti GE, Weinberg JB, Morrison VA, Link BK, Call TG, Caporaso NE, Cerhan JR. Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL. Blood. 2011 Feb 10;117(6):1911–1916.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

February 10, 2011

Volume

117

Issue

6

Start / End Page

1911 / 1916

Location

United States

Related Subject Headings

  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Odds Ratio
  • Male
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Interferon Regulatory Factors
  • Immunology
  • Humans
  • HLA-DRB5 Chains
  • HLA-DR Antigens