Abstract Despite limited discovery stages (<1,125 cases), genome-wide association studies (GWAS) have successfully identified 13 loci associated with risk of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL); however, these loci only explain a portion of the heritability. To identify additional genetic loci associated with CLL susceptibility, we conducted the largest meta-analysis of GWAS, to date, including 3,100 CLL cases and 7,667 controls of European ancestry from 25 independent studies genotyped on four different SNP microarrays. Association testing was conducted assuming a log-additive genetic model, adjusting for age, sex, and significant principal components. Meta-analyses were performed using the fixed effects inverse variance method based on the beta estimates and standard errors from each study. Promising loci were taken forward for replication in three additional studies totaling 788 cases and 4,872 controls. In the meta-analysis of both the discovery and replication studies, we conclusively identified ten independent SNPs in nine novel loci that reached genome-wide significance (P<5 x 10−8): 10q23.31 (FAS; P=1.22x10−14), 18q21.33 (BCL2; P=2.66x10−12 and P=7.76x10−11), 11p15.5 (C11orf21; P=2.15x10−10), 4q25 (LEF1; P=4.24x10−10), 2q33.1 (CASP8; P=2.50x10−9), 9p21.3 (CDKN2B-AS1; P=1.27x10−8), 18q21.32 (PMAIP1; P=2.51x10−8), 15q15.1 (BMF; P=2.71x10−10), and 2p22.2 (QPCT; P=1.68x10−8) as well as an independent signal at an established locus (2q13, ACOXL, P=2.08x10−18). We also found evidence for two additional promising loci that reached marginal genome-wide significance (P<2.0x10−7) at 8q22.3 (ODF1; P=5.40x10−8) and 5p15.33 (TERT; P=1.92x10−7). Although further studies are required, the proximity of five of the novel loci to genes involved in apoptosis suggests a possible unifying underlying biological mechanism. Together with the previously established loci, these genetic loci explain ~17% of the familial risk of CLL. Citation Format: Sonja I. Berndt, Christine F. Skibola, Vijai Joseph, Nicola J. Camp, Alexandra Nieters, Zhaoming Wang, Wendy Cozen, Alain Monnereau, Rachel S. Kelly, Silvia de Sanjose, Martha S. Linet, Elio Riboli, Paolo Vineis, Henrik Hjalgrim, James R. Cerhan, Stephen J. Chanock, Nathaniel Rothman, Susan L. Slager. Meta-analysis of genome-wide association studies identifies multiple loci associated with chronic lymphocytic leukemia. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-23. doi:10.1158/1538-7445.AM2013-LB-23