Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P=3.95 × 10(-15)) and HLA-B (rs2922994, P=2.43 × 10(-9)) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility.

] Cancer Control Research BC Cancer Agency Vancouver British Columbia Canada V5Z1L3 [2] School of Population and Public Health University of British Columbia Vancouver British Columbia Canada V6T1Z3

] Cancer Epidemiology Centre Cancer Council Victoria Melbourne Victoria 3053 Australia [2] Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health University of Melbourne Carlton Victoria 3010 Australia

] Cancer Epidemiology Centre Cancer Council Victoria Melbourne Victoria 3053 Australia [2] Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health University of Melbourne Carlton Victoria 3010 Australia [3] Human Genetics Foundation Turin 10126 Italy

] Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts 02115 USA [2] Department of Epidemiology Harvard School of Public Health Boston Massachusetts 02115 USA

] Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts 02115 USA [2] Department of Epidemiology Harvard School of Public Health Boston Massachusetts 02115 USA [3] Department of Nutrition Harvard School of Public Health Boston Massachusetts 02115 USA

] Department of Epidemiology Harvard School of Public Health Boston Massachusetts 02115 USA [2] College of Information Science and Technology Dalian Maritime University Dalian 116026 China

] Department of Epidemiology Harvard School of Public Health Boston Massachusetts 02115 USA [2] Department of Biostatistics Harvard School of Public Health Boston Massachusetts 02115 USA

] Department of Epidemiology Harvard School of Public Health Boston Massachusetts 02115 USA [2] Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm 17177 Sweden

] Department of Epidemiology Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht 3584 CX The Netherlands [2] Institute for Risk Assessment Sciences Utrecht University Utrecht 3508 TD The Netherlands

] Department of Epidemiology Research Division of Health Surveillance and Research Statens Serum Institut Copenhagen 2300 Denmark [2] Department of Medicine Stanford University School of Medicine Stanford California 94305 USA

] Department of Epidemiology School of Public Health and Comprehensive Cancer Center Birmingham Alabama 35233 USA [2] Division of Environmental Health Sciences University of California Berkeley School of Public Health Berkeley California 94720 USA

] Department of Epidemiology University of North Carolina at Chapel Hill Chapel Hill North Carolina 27599 USA [2] Carolina Center for Genome Sciences University of North Carolina at Chapel Hill Chapel Hill North Carolina 27599 USA

] Department of Medical Genetics Center for Molecular Medicine University Medical Center Utrecht Utrecht 3584 CG The Netherlands [2] Department of Epidemiology Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht 3584 CX The Netherlands

] Department of Oncology and Pathology Karolinska Institutet Karolinska University Hospital Solna Stockholm 17176 Sweden [2] Department of Radiology Oncology and Radiation Science Uppsala University Uppsala 75105 Sweden

] Department of Population Health New York University School of Medicine New York New York 10016 USA [2] Cancer Institute New York University School of Medicine New York New York 10016 USA

] Department of Preventive Medicine USC Keck School of Medicine University of Southern California Los Angeles California 90033 USA [2] Norris Comprehensive Cancer Center USC Keck School of Medicine University of Southern California Los Angeles California 90033 USA

] Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle Washington 98117 USA [2] Department of Environmental and Occupational Health Drexel University School of Public Health Philadelphia Pennsylvania 19104 USA

] Environmental Epidemiology of Cancer Group Inserm Centre for research in Epidemiology and Population Health U1018 Villejuif F 94807 France [2] UMRS 1018 Univ Paris Sud Villejuif F 94807 France

] Environmental Epidemiology of Cancer Group Inserm Centre for research in Epidemiology and Population Health U1018 Villejuif F 94807 France [2] UMRS 1018 Univ Paris Sud Villejuif F 94807 France [3] Registre des hémopathies malignes de la Gironde Institut Bergonié Bordeaux 33076 France

] Genome Sciences Centre BC Cancer Agency Vancouver British Columbia Canada V5Z1L3 [2] Department of Biomedical Physiology and Kinesiology Simon Fraser University Burnaby British Columbia Canada V5A1S6

] MRC PHE Centre for Environment and Health School of Public Health Imperial College London London W2 1PG UK [2] Human Genetics Foundation Turin 10126 Italy

] Pathology Australian School of Advanced Medicine Macquarie University Sydney New South Wales 2109 Australia [2] Department of Histopathology Douglass Hanly Moir Pathology Macquarie Park New South Wales 2113 Australia

] Unit of Infections and Cancer Barcelona 8036 Spain

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

Center For Chronic Immunodeficiency University Medical Center Freiburg Freiburg 79108 Germany

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

Department of Biomedical Science University of Cagliari Monserrato Cagliari 09042 Italy

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

Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute and MF MU Brno 65653 Czech Republic

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

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

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

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

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

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

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

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

Department of Health Sciences Research Mayo Clinic Rochester Minnesota 55905 USA

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

Department of Health Studies University of Chicago Chicago Illinois 60637 USA

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

Department of Medicine Mayo Clinic Rochester Minnesota 55905 USA

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

Department of Medicine Solna Karolinska Institutet Stockholm 17176 Sweden

Department of Pathological Anatomy University of Bari Bari 70124 Italy

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

Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda Maryland 20892 USA

Division of Cancer Epidemiology German Cancer Research Center Heidelberg 69120 Germany

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

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

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

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

Environmental and Occupational Epidemiology Unit Cancer Prevention and Research Institute Florence 50139 Italy

Epidemiology Research Program American Cancer Society Atlanta Georgia 30303 USA

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

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

Health Studies Sector Westat Rockville Maryland 20850 USA

Interdisciplinary Department of Medicine University of Bari Bari 70124 Italy

MRC PHE Centre for Environment and Health School of Public Health Imperial College London London W2 1PG UK

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

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

Sydney School of Public Health The University of Sydney Sydney New South Wales 2006 Australia

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

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