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.

Cancer Control Research BC Cancer Agency Vancouver BC V5Z 1L3 Canada; School of Population and Public Health University of British Columbia Vancouver BC V6T 1Z3 Canada

Cancer Epidemiology Centre Cancer Council Victoria Melbourne VIC 3053 Australia; Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health University of Melbourne Carlton VIC 3010 Australia

Cancer Epidemiology Unit University of Oxford Oxford OX3 7LF UK

Cancer Genomics Research Laboratory Division of Cancer Epidemiology and Genetics National Cancer Institute NIH Gaithersburg MD 20877 USA

Center for Chronic Immunodeficiency University Medical Center Freiburg Freiburg Baden Württemberg 79108 Germany

Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston MA 02115 USA

Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston MA 02115 USA; Department of Epidemiology Harvard School of Public Health Boston MA 02115 USA

Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston MA 02115 USA; Department of Epidemiology Harvard School of Public Health Boston MA 02115 USA; Department of Nutrition Harvard School of Public Health Boston MA 02115 USA

Department of Anatomical Pathology Australian School of Advanced Medicine Macquarie University Sydney NSW 2109 Australia; Department of Histopathology Douglass Hanly Moir Pathology Macquarie Park NSW 2113 Australia

Department of Biomedical Science University of Cagliari Monserrato Cagliari 09042 Italy

Department of Biostatistics University of Alabama at Birmingham Birmingham AL 35233 USA

Department of Biostatistics Yale School of Public Health New Haven CT 06520 USA

Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute and MF MU Brno 656 53 Czech Republic

Department of Cancer Etiology City of Hope Beckman Research Institute Duarte CA 91030 USA

Department of Chronic Disease Prevention National Institute for Health and Welfare Helsinki 00271 Finland

Department of Clinical Sciences Division of Internal Medicine Skåne University Hospital Lund University Malmö 205 02 Sweden

Department of Environmental Health Sciences Yale School of Public Health New Haven CT 06520 USA

Department of Epidemiology and Biostatistics University of California San Francisco San Francisco CA 94118 USA

Department of Epidemiology Harvard School of Public Health Boston MA 02115 USA

Department of Epidemiology Harvard School of Public Health Boston MA 02115 USA; College of Information Science and Technology Dalian Maritime University Dalian Liaoning Province 116026 China

Department of Epidemiology Harvard School of Public Health Boston MA 02115 USA; Department of Biostatistics Harvard School of Public Health Boston MA 02115 USA

Department of Epidemiology Harvard School of Public Health Boston MA 02115 USA; Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm 17177 Sweden

Department of Epidemiology M D Anderson Cancer Center Houston TX 77030 USA

Department of Epidemiology Research Division of Health Surveillance and Research Statens Serum Institut Copenhagen 2300 Denmark

Department of Epidemiology Research Division of Health Surveillance and Research Statens Serum Institut Copenhagen 2300 Denmark; Department of Medicine Stanford University School of Medicine Stanford CA 94305 USA

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

Department of Epidemiology University of North Carolina at Chapel Hill Chapel Hill NC 27599 USA; Carolina Center for Genome Sciences University of North Carolina at Chapel Hill Chapel Hill NC 27599 USA

Department of Family Medicine and Public Health Sciences Wayne State University Detroit MI 48201 USA

Department of Health Sciences Research Mayo Clinic Rochester MN 55905 USA

Department of Health Sciences University of York York YO10 5DD UK

Department of Health Studies University of Chicago Chicago IL 60637 USA

Department of Hematology Hospices Civils de Lyon Pierre benite Cedex 69495 France; Department of Hematology Université Lyon 1 Pierre benite Cedex 69495 France; Laboratoire de Biologie Moléculaire de la Cellule UMR 5239 Centre National de la Recherche Scientifique Pierre benite Cedex 69495 France

Department of Hematology Ospedale Nord Taranto 74100 Italy

Department of Internal Medicine Carver College of Medicine The University of Iowa Iowa City IA 52242 USA

Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm 17177 Sweden; Department of Community Medicine Faculty of Health Sciences University of Tromsø Breivika 9037 Norway; Cancer Registry of Norway Oslo 0304 Norway; Department of Genetic Epidemiology Folkhalsan Research Center Helsinki 00250 Finland

Department of Medical Genetics and of Epidemiology University Medical Center Utrecht Utrecht 3584 CG the Netherlands; Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht 3584 CX the Netherlands

Department of Medicine Mayo Clinic Rochester MN 55905 USA

Department of Medicine Memorial Sloan Kettering Cancer Center New York NY 10065 USA

Department of Medicine Solna Karolinska Institutet Stockholm 17176 Sweden

Department of Oncology and Pathology Karolinska Institutet Karolinska University Hospital Solna Stockholm 17176 Sweden; Department of Radiology Oncology and Radiation Science Uppsala University Uppsala 75105 Sweden

Department of Population Health New York University School of Medicine New York NY 10016 USA; Cancer Institute New York University School of Medicine New York NY 10016 USA

Department of Preventive Medicine USC Keck School of Medicine University of Southern California Los Angeles CA 90033 USA; Norris Comprehensive Cancer Center USC Keck School of Medicine University of Southern California Los Angeles CA 90033 USA

Department of Public Health Clinical and Molecular Medicine University of Cagliari Monserrato Cagliari 09042 Italy

Departments of Laboratory Medicine and Pathology Memorial Sloan Kettering Cancer Center New York NY 10065 USA

Division of Cancer Epidemiology and Genetics National Cancer Institute NIH Bethesda MD 20892 USA

Division of Cancer Epidemiology German Cancer Research Center Heidelberg Baden Württemberg 69120 Germany

Division of Endocrinology Diabetes and Metabolism The Ohio State University Columbus OH 43210 USA

Division of Environmental Health Sciences University of California Berkeley School of Public Health Berkeley CA 94720 USA

Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle WA 98117 USA

Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle WA 98117 USA; Department of Environmental and Occupational Health Drexel University School of Public Health Philadelphia PA 19104 USA

EA 4184 Registre des Hémopathies Malignes de Côte d'Or University of Burgundy and Dijon University Hospital Dijon 21070 France

Environmental Epidemiology of Cancer Group Inserm Centre for Research in Epidemiology and Population Health U1018 Villejuif Cedex 94807 France; UMRS 1018 Université Paris Sud Villejuif Cedex 94807 France

Environmental Epidemiology of Cancer Group Inserm Centre for Research in Epidemiology and Population Health U1018 Villejuif Cedex 94807 France; UMRS 1018 Université Paris Sud Villejuif Cedex 94807 France; Registre des hémopathies malignes de la Gironde Institut Bergonié Bordeaux Cedex 33076 France

Epidemiology Research Program American Cancer Society Atlanta GA 30303 USA

Genetic Cancer Susceptibility Group Section of Genetics International Agency for Research on Cancer Lyon 69372 France

Genome Sciences Centre BC Cancer Agency Vancouver BC V5Z 1L3 Canada; Department of Biomedical Physiology and Kinesiology Simon Fraser University Burnaby BC V5A 1S6 Canada

Group of Genetic Epidemiology Section of Genetics International Agency for Research on Cancer Lyon 69372 France

Health Department BioDonostia Research Institute Basque Region 20014 Spain

Health Studies Sector Westat Rockville MD 20850 USA

Human Genetics Foundation Turin 10126 Italy; Cancer Epidemiology Centre Cancer Council Victoria Melbourne VIC 3053 Australia; Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health University of Melbourne Carlton VIC 3010 Australia

Human Genetics Foundation Turin 10126 Italy; MRC PHE Centre for Environment and Health School of Public Health Imperial College London London W2 1PG UK

Human Genetics Genome Institute of Singapore Singapore 138672 Singapore

Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht 3584 CX the Netherlands; Institute for Risk Assessment Sciences Utrecht University Utrecht 3508 TD the Netherlands

Laboratoire de Biologie Moléculaire de la Cellule UMR 5239 Centre National de la Recherche Scientifique Pierre benite Cedex 69495 France; Department of Hematology Centre Léon Bérard Lyon 69008 France

MRC PHE Centre for Environment and Health School of Public Health Imperial College London London W2 1PG UK; Department of Epidemiology Harvard School of Public Health Boston MA 02115 USA

Prince of Wales Clinical School University of New South Wales Sydney NSW 2052 Australia

School of Nursing and Human Sciences Dublin City University Dublin 9 Ireland

Sydney School of Public Health The University of Sydney Sydney NSW 2006 Australia

The Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York NY 10029 USA

Unit of Infections and Cancer Barcelona 8036 Spain

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