Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

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Law, PJ; Berndt, SI; Speedy, HE; Camp, NJ; Sava, GP; Skibola, CF; Holroyd, A; Joseph, V; Sunter, NJ; Nieters, A; ...Date
2017-02-06Source Title
Nature CommunicationsPublisher
NATURE PUBLISHING GROUPAffiliation
Melbourne School of Population and Global HealthClinical Pathology
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Law, 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 Status
Open AccessAbstract
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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