Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region
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Publication date
2014-10-02
Authors
Skibola, Christine F.
Berndt, Sonja I.
Vijai, Joseph
Conde, Lucia
Wang, Zhaoming
Yeager, Meredith
de Bakker, Paul I. W.
Birmann, Brenda M.
Vajdic, Claire M.
Foo, Jia-Nee
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Article
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Abstract
Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 x 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 x 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 x 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 x 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 x 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DR beta 1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (P-omnibus = 4.20 x 10(-67) to 2.67 x 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [ORper-allele] = 1.44; p = 4.59 x 10(-16)) and rs3130437 in HLA class I (ORper-allele = 1.23; p = 8.23 x 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.
Keywords
CLASS-I, VARIANTS, EXPRESSION, UNIVERSITY, RESOURCE, PEPTIDE, RISK, SNPS, TOOL, SET
Citation
Skibola, C F, Berndt, S I, Vijai, J, Conde, L, Wang, Z, Yeager, M, de Bakker, P I W, Birmann, B M, Vajdic, C M, Foo, J-N, Bracci, P M, Vermeulen, R C H, Slager, S L, de Sanjose, S, Wang, S S, Linet, M S, Salles, G, Lan, Q, Severi, G, Hjalgrim, H, Lightfoot, T, Melbye, M, Gu, J, Ghesquieres, H, Link, B K, Morton, L M, Holly, E A, Smith, A, Tinker, L F, Teras, L R, Kricker, A, Becker, N, Purdue, M P, Spinelli, J J, Zhang, Y, Giles, G G, Vineis, P, Monnereau, A, Bertrand, K A, Albanes, D, Zeleniuch-Jacquotte, A, Gabbas, A, Chung, C C, Burdett, L, Hutchinson, A, Lawrence, C, Montalvan, R, Liang, L, Huang, J, Ma, B, Liu, J, Adami, H-O, Glimelius, B, Ye, Y, Nowakowski, G S, Dogan, A, Thompson, C A, Habermann, T M, Novak, A J, Liebow, M, Witzig, T E, Weiner, G J, Schenk, M, Hartge, P, De Roos, A J, Cozen, W, Zhi, D, Akers, N K, Riby, J, Smith, M T, Lacher, M, Villano, D J, Maria, A, Roman, E, Kane, E, Jackson, R D, North, K E, Diver, W R, Turner, J, Armstrong, B K, Benavente, Y, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, Staines, A, McKay, J, Brooks-Wilson, A R, Zheng, T, Holford, T R, Chamosa, S, Kaaks, R, Kelly, R S, Ohlsson, B, Travis, R C, Weiderpass, E, Clave, J, Giovannucci, E, Kraft, P, Virtamo, J, Mazza, P, Cocco, P, Ennas, M G, Chiu, B C H, Fraumeni, J R, Nieters, A, Offit, K, Wu, X, Cerhan, J R, Smedby, K E, Chanock, S J & Rothman, N 2014, 'Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region', American Journal of Human Genetics, vol. 95, no. 4, pp. 462-471. https://doi.org/10.1016/j.ajhg.2014.09.004