全基因组关联研究确定了HLA区域之外的五个滤泡性淋巴瘤易感位点。
Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region.
作者信息
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, Bracci Paige M, Vermeulen Roel C H, 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, Mazza Patrizio, Cocco Pierluigi, Ennas Maria Grazia, Chiu Brian C H, Fraumeni Joseph F, Nieters Alexandra, Offit Kenneth, Wu Xifeng, Cerhan James R, Smedby Karin E, Chanock Stephen J, Rothman Nathaniel
机构信息
Department of Epidemiology, School of Public Health and Comprehensive Cancer Center, Birmingham, AL 35233, USA; Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, CA 94720, USA.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
出版信息
Am J Hum Genet. 2014 Oct 2;95(4):462-71. doi: 10.1016/j.ajhg.2014.09.004.
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.
此前，滤泡性淋巴瘤（FL）的全基因组关联研究（GWAS）已鉴定出人类白细胞抗原（HLA）基因变异。为了鉴定其他FL易感位点，我们对4523例欧洲血统的病例受试者和13344例对照受试者进行了大规模两阶段GWAS。五个非HLA位点与FL风险相关：CXCR5附近的11q23.3（rs4938573，p = 5.79×10⁻²⁰）；ETS1附近的11q24.3（rs4937362，p = 6.76×10⁻¹¹）；LPP中的3q28（rs6444305，p = 1.10×10⁻¹⁰）；BCL2附近的18q21.33（rs17749561，p = 8.28×10⁻¹⁰）；以及PVT1附近的8q24.21（rs13254990，p = 1.06×10⁻⁸）。在对HLA区域的分析中，我们在第11、13、28和30位鉴定出四个与FL风险相关的连锁HLA-DRβ1多等位氨基酸（pomnibus = 4.20×10⁻⁶⁷至2.67×10⁻⁷⁰）。其他独立信号包括HLA II类中的rs17203612（优势比[OR（每等位基因）]= 1.44；p = 4.59×10⁻¹⁶）和HLA I类中的rs3130437（OR（每等位基因）= 1.23；p = 8.23×10⁻⁹）。我们的研究结果进一步扩大了与FL相关的位点数量，并提供了证据表明HLA区域外的多个常见变异对FL风险有重大贡献。
Zotero 插件