Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region.

Research output: Contribution to journalArticle

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.

Details

Authors
  • 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
  • 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
  • Jenny 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
  • 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
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
Original languageEnglish
Pages (from-to)462-471
JournalAmerican Journal of Human Genetics
Volume95
Issue number4
Publication statusPublished - 2014
Publication categoryResearch
Peer-reviewedYes