Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
Publication date
2017-02-06
Authors
Law, Philip J
Berndt, Sonja I.
Speedy, Helen E
Camp, Nicola J
Sava, Georgina P
Skibola, Christine F.
Holroyd, Amy
Joseph, Vijai
Sunter, Nicola J
Nieters, Alexandra
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Article
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Abstract
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.
Keywords
SDG 3 - Good Health and Well-being
Citation
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, Cozen, W, Majid, A, Smedby, K E, Lan, Q, Dearden, C, Brooks-Wilson, A R, Hall, A G, Purdue, M P, Mainou-Fowler, T, Vajdic, C M, Jackson, G H, Cocco, P, Marr, H, Zhang, Y, Zheng, T, Giles, G G, Lawrence, C, Call, T G, Liebow, M, Melbye, M, Glimelius, B, Mansouri, L, Glenn, M, Curtin, K, Diver, W R, Link, B K, Conde, L, Bracci, P M, Holly, E A, Jackson, R D, Tinker, L F, Benavente, Y, Boffetta, P, Brennan, P, Maynadie, M, McKay, J, Albanes, D, Weinstein, S, Wang, Z, Caporaso, N E, Morton, L M, Severson, R K, Riboli, E, Vineis, P, Vermeulen, R C H, Southey, M C, Milne, R L, Clavel, J, Topka, S, Spinelli, J, Kraft, P, Ennas, M G, Summerfield, G, Ferri, G M, Harris, R J, Miligi, L, Pettitt, A R, North, K E, Allsup, D J, Fraumeni, J F, Bailey, J R, Offit, K, Pratt, G, Hjalgrim, H, Pepper, C, Chanock, S J, Fegan, C, Rosenquist, R, De Sanjose, S, Carracedo, A, Dyer, M J S, Catovsky, D, Campo, E, Cerhan, J R, Allan, J M, Rothman, N, Houlston, R S & Slager, S L 2017, 'Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia', Nature Communications, vol. 8, pp. 14175. https://doi.org/10.1038/ncomms14175