Journal article
Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL
Blood, Vol.117(6), pp.1911-1916
Lymphoid Neoplasia
02/10/2011
DOI: 10.1182/blood-2010-09-308205
PMCID: PMC3056639
PMID: 21131588
Abstract
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.
Details
- Title: Subtitle
- Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL
- Creators
- Susan L Slager - Mayo Clinic College of Medicine, Rochester, MNKari G Rabe - Mayo Clinic College of Medicine, Rochester, MNSara J Achenbach - Mayo Clinic College of Medicine, Rochester, MNCeline M Vachon - Mayo Clinic College of Medicine, Rochester, MNLynn R Goldin - Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MDSara S Strom - University of Texas M. D. Anderson Cancer Center, Houston, TXMark C Lanasa - Duke University Medical Center, Durham, NCLogan G Spector - University of Minnesota, Minneapolis, MNLaura Z Rassenti - Moores Cancer Center, University of California-San Diego Medical Center, La Jolla, CAJose F Leis - Mayo Clinic College of Medicine, Rochester, MNNicola J Camp - University of Utah School of Medicine, Salt Lake City, UTMartha Glenn - University of Utah School of Medicine, Salt Lake City, UTNeil E Kay - Mayo Clinic College of Medicine, Rochester, MNJulie M Cunningham - Mayo Clinic College of Medicine, Rochester, MNCurtis A Hanson - Mayo Clinic College of Medicine, Rochester, MNGerald E Marti - US Food and Drug Administration, Bethesda, MDJ. Brice Weinberg - Duke University Medical Center, Durham, NCVicki A Morrison - University of Minnesota, Minneapolis, MNBrian K Link - University of Iowa, Iowa City, IATimothy G Call - Mayo Clinic College of Medicine, Rochester, MNNeil E Caporaso - Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MDJames R Cerhan - Mayo Clinic College of Medicine, Rochester, MN
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.117(6), pp.1911-1916
- Series
- Lymphoid Neoplasia
- DOI
- 10.1182/blood-2010-09-308205
- PMID
- 21131588
- PMCID
- PMC3056639
- NLM abbreviation
- Blood
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Publisher
- American Society of Hematology
- Grant note
- CA118444; CA92153; 1 UL1 RR024150 / National Institutes of Health
- Language
- English
- Date published
- 02/10/2011
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Internal Medicine
- Record Identifier
- 9984094554102771
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