Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
AuthorLaw, PJ; Berndt, SI; Speedy, HE; Camp, NJ; Sava, GP; Skibola, CF; Holroyd, A; Joseph, V; Sunter, NJ; Nieters, A; ...
Source TitleNature Communications
PublisherNATURE PUBLISHING GROUP
AffiliationMelbourne School of Population and Global Health
Document TypeJournal Article
CitationsLaw, P. J., Berndt, S. I., Speedy, H. E., Camp, N. J., Sava, G. P., Skibola, C. F., Holroyd, A., Joseph, V., Sunter, N. J., Nieters, A., Bea, S., Monnereau, A., Martin-Garcia, D., Goldin, L. R., Clot, G., Teras, L. R., Quintela, I., Birmann, B. M., Jayne, S. ,... Slager, S. L. (2017). Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia. NATURE COMMUNICATIONS, 8 (1), https://doi.org/10.1038/ncomms14175.
Access StatusOpen Access
Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10-13), 1q42.13 (rs41271473, P=1.06 × 10-10), 4q24 (rs71597109, P=1.37 × 10-10), 4q35.1 (rs57214277, P=3.69 × 10-8), 6p21.31 (rs3800461, P=1.97 × 10-8), 11q23.2 (rs61904987, P=2.64 × 10-11), 18q21.1 (rs1036935, P=3.27 × 10-8), 19p13.3 (rs7254272, P=4.67 × 10-8) and 22q13.33 (rs140522, P=2.70 × 10-9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.
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