학술논문
Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region
Document Type
article
Author
Skibola, Christine F; Berndt, Sonja I; Vijai, Joseph; Conde, Lucia; Wang, Zhaoming; Yeager, Meredith; de Bakker, Paul IW; Birmann, Brenda M; Vajdic, Claire M; Foo, Jia-Nee; Bracci, Paige M; Vermeulen, Roel CH; Slager, Susan L; de Sanjose, Silvia; Wang, Sophia S; Linet, Martha S; Salles, Gilles; Lan, Qing; Severi, Gianluca; Hjalgrim, Henrik; Lightfoot, Tracy; Melbye, Mads; Gu, Jian; Ghesquières, Hervé; Link, Brian K; Morton, Lindsay M; Holly, Elizabeth A; Smith, Alex; Tinker, Lesley F; Teras, Lauren R; Kricker, Anne; Becker, Nikolaus; Purdue, Mark P; Spinelli, John J; Zhang, Yawei; Giles, Graham G; Vineis, Paolo; Monnereau, Alain; Bertrand, Kimberly A; Albanes, Demetrius; Zeleniuch-Jacquotte, Anne; Gabbas, Attilio; Chung, Charles C; Burdett, Laurie; Hutchinson, Amy; Lawrence, Charles; Montalvan, Rebecca; Liang, Liming; Huang, Jinyan; Ma, Baoshan; Liu, Jianjun; Adami, Hans-Olov; Glimelius, Bengt; Ye, Yuanqing; Nowakowski, Grzegorz S; Dogan, Ahmet; Thompson, Carrie A; Habermann, Thomas M; Novak, Anne J; Liebow, Mark; Witzig, Thomas E; Weiner, George J; Schenk, Maryjean; Hartge, Patricia; De Roos, Anneclaire J; Cozen, Wendy; Zhi, Degui; Akers, Nicholas K; Riby, Jacques; Smith, Martyn T; Lacher, Mortimer; Villano, Danylo J; Maria, Ann; Roman, Eve; Kane, Eleanor; Jackson, Rebecca D; North, Kari E; Diver, W Ryan; Turner, Jenny; Armstrong, Bruce K; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; McKay, James; Brooks-Wilson, Angela R; Zheng, Tongzhang; Holford, Theodore R; Chamosa, Saioa; Kaaks, Rudolph; Kelly, Rachel S; Ohlsson, Bodil; Travis, Ruth C; Weiderpass, Elisabete; Clavel, Jacqueline; Giovannucci, Edward; Kraft, Peter; Virtamo, Jarmo
Source
American Journal of Human Genetics. 95(4)
Subject
Language
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 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [OR(per-allele)] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (OR(per-allele) = 1.23; p = 8.23 × 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.