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

TitleGenome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia.
Publication TypeJournal Article
Year of Publication2013
AuthorsBerndt SI, Skibola CF, Joseph V, Camp NJ, Nieters A, Wang Z, Cozen W, Monnereau A, Wang SS, Kelly RS et al.
JournalNat Genet
Volume45
Issue8
Pagination868-76
Date Published2013 Aug
ISSN1546-1718
KeywordsCase-Control Studies, Chromosomes, Human, Pair 2, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Recombination, Genetic, Risk
Abstract

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.

DOI10.1038/ng.2652
Alternate JournalNat. Genet.
PubMed ID23770605
PubMed Central IDPMC3729927
Grant ListK08 CA134919 / CA / NCI NIH HHS / United States
N01 CN045165 / CN / NCI NIH HHS / United States
N01RC37004 / RC / CCR NIH HHS / United States
P01 CA055075 / CA / NCI NIH HHS / United States
P50 CA097274 / CA / NCI NIH HHS / United States
R01 CA092153 / CA / NCI NIH HHS / United States
R01 CA104682 / CA / NCI NIH HHS / United States
R01 CA122663 / CA / NCI NIH HHS / United States
R01 CA129539 / CA / NCI NIH HHS / United States
R01 CA134674 / CA / NCI NIH HHS / United States
R01 CA148690 / CA / NCI NIH HHS / United States
R01 CA149445 / CA / NCI NIH HHS / United States
R01 CA154643 / CA / NCI NIH HHS / United States
R03 CA143947 / CA / NCI NIH HHS / United States
R03 CA150037 / CA / NCI NIH HHS / United States
R25 CA098566 / CA / NCI NIH HHS / United States
U01 CA118444 / CA / NCI NIH HHS / United States