Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region

Christine F. Skibola*, Sonja I. Berndt, Joseph Vijai, Lucia Conde, Zhaoming Wang, Meredith Yeager, Paul I. W. De Bakker, Brenda M. Birmann, Claire M. Vajdic, Jia Nee Foo, Paige M. Bracci, Roel C.H. Vermeulen, Susan L. Slager, Silvia De Sanjose, Sophia S. Wang, Martha S. Linet, Gilles Salles, Qing Lan, Gianluca Severi, Henrik Hjalgrim & 92 others Tracy Lightfoot, Mads Melbye, Jian Gu, Hervé Ghesquières, Brian K. Link, Lindsay M. Morton, Elizabeth A. Holly, Alex Smith, Lesley F. Tinker, Lauren R. Teras, Anne Kricker, Nikolaus Becker, Mark P. Purdue, John J. Spinelli, Yawei Zhang, Graham G. Giles, Paolo Vineis, Alain Monnereau, Kimberly A. Bertrand, Demetrius Albanes, Anne Zeleniuch-Jacquotte, Attilio Gabbas, Charles C. Chung, Laurie Burdett, Amy Hutchinson, Charles Lawrence, Rebecca Montalvan, Liming Liang, Jinyan Huang, Baoshan Ma, Jianjun Liu, Hans Olov Adami, Bengt Glimelius, Yuanqing Ye, Grzegorz S. Nowakowski, Ahmet Dogan, Carrie A. Thompson, Thomas M. Habermann, Anne J. Novak, Mark Liebow, Thomas E. Witzig, George J. Weiner, Maryjean Schenk, Patricia Hartge, Anneclaire J. De Roos, Wendy Cozen, Degui Zhi, Nicholas K. Akers, Jacques Riby, Martyn T. Smith, Mortimer Lacher, Danylo J. Villano, Ann Maria, Eve Roman, Eleanor Kane, Rebecca D. Jackson, Kari E. North, W. Ryan Diver, Jennifer Turner, Bruce K. Armstrong, Yolanda Benavente, Paolo Boffetta, Paul Brennan, Lenka Foretova, Marc Maynadie, Anthony Staines, James McKay, Angela R. Brooks-Wilson, Tongzhang Zheng, Theodore R. Holford, Saioa Chamosa, Rudolph Kaaks, Rachel S. Kelly, Bodil Ohlsson, Ruth C. Travis, Elisabete Weiderpass, Jacqueline Clavel, Edward Giovannucci, Peter Kraft, Jarmo Virtamo, Patrizio Mazza, Pierluigi Cocco, Maria Grazia Ennas, Brian C.H. Chiu, Joseph F. Fraumeni, Alexandra Nieters, Kenneth Offit, Xifeng Wu, James R. Cerhan, Karin E. Smedby, Stephen J. Chanock, Nathaniel Rothman

*Corresponding author for this work

Research output: Contribution to journalArticle

62 Citations (Scopus)

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 [ORper-allele] = 1.44; p = 4.59 × 10 -16) and rs3130437 in HLA class I (ORper-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.

Original languageEnglish
Pages (from-to)462-471
Number of pages10
JournalAmerican Journal of Human Genetics
Volume95
Issue number4
DOIs
Publication statusPublished - 2014

Fingerprint Dive into the research topics of 'Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region'. Together they form a unique fingerprint.

  • Cite this