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

Reference Details

Berndt SI, Skibola CF, Joseph V, Camp NJ, Nieters A, Wang Z, Cozen W, Monnereau A, Wang SS, Kelly RS, Lan Q, Teras LR, Chatterjee N, Chung CC, Yeager M, Brooks-Wilson AR, Hartge P, Purdue MP, Birmann BM, Armstrong BK, Cocco P, Zhang Y, Severi G, Zeleniuch-Jacquotte A, Lawrence C, Burdette L, Yuenger J, Hutchinson A, Jacobs KB, Call TG, Shanafelt TD, Novak AJ, Kay NE, Liebow M, Wang AH, Smedby KE, Adami HO, Melbye M, Glimelius B, Chang ET, Glenn M, Curtin K, Cannon-Albright LA, Jones B, Diver WR, Link BK, Weiner GJ, Conde L, Bracci PM, Riby J, Holly EA, Smith MT, Jackson RD, Tinker LF, Benavente Y, Becker N, Boffetta P, Brennan P, Foretova L, Maynadie M, McKay J, Staines A, Rabe KG, Achenbach SJ, Vachon CM, Goldin LR, Strom SS, Lanasa MC, Spector LG, Leis JF, Cunningham JM, Weinberg JB, Morrison VA, Caporaso NE, Norman AD, Linet MS, De Roos AJ, Morton LM, Severson RK, Riboli E, Vineis P, Kaaks R, Trichopoulos D, Masala G, Weiderpass E, Chirlaque MD, Vermeulen RC, Travis RC, Giles GG, Albanes D, Virtamo J, Weinstein S, Clavel J, Zheng T, Holford TR, Offit K, Zelenetz A, Klein RJ, Spinelli JJ, Bertrand KA, Laden F, Giovannucci E, Kraft P, Kricker A, Turner J, Vajdic CM, Ennas MG, Ferri GM, Miligi L, Liang L, Sampson J, Crouch S, Park JH, North KE, Cox A, Snowden JA, Wright J, Carracedo A, Lopez-Otin C, Bea S, Salaverria I, Martin-Garcia D, Campo E, Fraumeni JF, Jr., de Sanjose S, Hjalgrim H, Cerhan JR, Chanock SJ, Rothman N, Slager SL (2013) Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia. Nat Genet 45:868-876

Abtract

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 x 10-14), 18q21.33 (BCL2, P = 7.76 x 10-11), 11p15.5 (C11orf21, P = 2.15 x 10-10), 4q25 (LEF1, P = 4.24 x 10-10), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10-9), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10-8), 18q21.32 (PMAIP1, P = 2.51 x 10-8), 15q15.1 (BMF, P = 2.71 x 10-10) and 2p22.2 (QPCT, P = 1.68 x 10-8), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10-18). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10-8) and 5p15.33 (TERT, P = 1.92 x 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.

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