Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.

Behavioral and Epidemiology Research Group American Cancer Society Atlanta Georgia

Bill Lyons Informatics Centre UCL Cancer Institute University College London Cancer Institute London England

California State University Sacramento Califonia

Canada's Michael Smith Genome Sciences Centre BC Cancer Agency Vancouver Canada

Cancer Epidemiology Division Cancer Council Victoria Melbourne Australia

Cancer Epidemiology Unit University of Oxford Oxford England

Center for Neuroengineering and Therapeutics Department of Neurology Hospital of the University of Pennsylvania Philadelphia Pennsylvania

Center of Research in Epidemiology and Statistics Sorbonne Epidemiology of Childhood and Adolescent Cancer Group INSERM Paris France

Centre de Recherche en Cancerologie de Lyon Lyon France

Centre de Recherche en Transplantation et Immunologie Université de Nantes Centre Hospitalier Universitaire Nantes France

Centre for Big Data Research in Health University of New South Wales Kensington Australia

Centre for Epidemiology and Biostatistics University of Melbourne Melbourne Australia

Centre for Epidemiology and Intelligence Cancer Council Australia Melbourne Australia

Centre of Chronic Immunodeficiency University Medical Centre Freiburg Freiburg im Breisgau Germany

Centro de Investigación Biomédica en Red Epidemiología y Salud Pública Madrid Spain

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

Clinical Effectiveness Research Group Institute of Health University of Oslo Oslo Norway

Clinical Epidemiology McGill University Health Centre Research Institute Montreal Canada

Clinical School Concord Hospital University of Sydney Sydney Australia

College of Medicine California Northstate University Elk Grove California

Department of Biomedical Informatics University of Utah Salt Lake Utah

Department of Biomedical Physiology and Kinesiology Simon Fraser University Burnaby Canada

Department of Cancer Biology and Genetics Memorial Sloan Kettering Cancer Center New York New York

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

Department of Clinical Pathology Genetic Epidemiology Laboratory University of Melbourne Melbourne Australia

Department of Environmental Epidemiology of Cancers INSERM Paris France

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

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

Department of Epidemiology Harvard T H Chan School of Public Health Boston Massachusetts

Department of Epidemiology Research Statens Serum Institut København Denmark

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

Department of Health Sciences Research Mayo Clinic Rochester Minnesota

Department of Health Sciences University of York York England

Department of Immunology Genetics and Pathology Uppsala Universitet Uppsala Sweden

Department of Internal Medicine Huntsman Cancer Institute University of Utah School of Medicine Salt Lake Utah

Department of Internal Medicine Mayo Clinic Rochester Minnesota

Department of Medical and Molecular Genetics King's College London London England

Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden

Department of Medical Sciences and Public Health University of Cagliari Cagliari Sardinia Italy

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

Department of Medicine Universita degli Studi di Perugia Perugia Italy

Department of Neurology University of California San Francisco California

Department of Obstetrics and Gynecology Department of Population Health Department of Environmental Medicine NYU School of Medicine New York New York

Department of Pediatrics University of Chicago Chicago Illinois

Department of Population Sciences City of Hope and the Beckman Research Institute Duarte California

Department of Preventive Medicine University of Southern California Los Angeles Califonia

Departments of Epidemiology and Biostatistics Harvard School of Public Health Boston Massachusetts

Departments of Preventive Medicine and Pathology Norris Comprehensive Cancer Center and Hospital University of Southern California Los Angeles California

Division of Cancer Biology National Cancer Institute Bethesda Maryland

Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda Maryland

Division of Cancer Epidemiology Deutsches Krebsforschungszentrum Heidelberg Germany

Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany

Division of Clinical Epidemiology Department of Medicine Karolinska Institutet Solna Sweden

Division of Environmental Epidemiology Institute for Risk Assessment Science Utrecht University Utrecht Netherlands

Division of Rheumatology Department of Medicine Karolinska Institutet Stockholm Sweden

Environmental and Occupational Epidemiology Branch Cancer Risk Factors and Lifestyle Epidemiology Unit Institute for Cancer Research Prevention and Clinical Network Florence Florence Italy

Faculty of Medicine McGill University Montreal Canada

Hematology Department Centre Hospitalier Universitaire de Lyon Lyon France

Internal Medicine University of Iowa Hospitals and Clinics Iowa City Iowa

International Agency for Research on Cancer Lyon France

Lymphoid Malignancies Unit Henri Mondor Hospital University Paris Est Créteil Paris France

Medicina Traslazionale Università del Piemonte Orientale Vercelli Italy

Memorial Sloan Kettering Cancer Center New York New York

Norris Comprehensive Cancer Center and Hospital University of Southern California Los Angeles California

Population Oncology British Columbia Cancer Agency Vancouver Canada

Precision Medicine School of Clinical Sciences Monash University Melbourne Australia

Registre des Hémopathies Malignes de la Gironde Institut Bergonie Bordeaux France

Reproductive Health Global Program PATH School of Public Health University of Washington Seattle Washington USA

Santé Publique Clinique des Données Centre Hospitalier Universitaire de Nantes INSERM Nantes France

School of Biomedical Sciences University of Calgary Calgary Canada

School of Medicine Emory University Atlanta Georgia

School of Medicine Stanford University Stanford California

School of Nursing and Human Science Dublin City University Dublin Ireland

School of Population and Public Health University of British Columbia Vancouver British Columbia Canada

School of Public Health Brown University Providence Rhode Island

School of Public Health Imperial College London London England

The University of Burgundy Franche Comté and CHU Dijon Bourgogne Registre des Hémopathies Malignes de Côte d'Or INSERM U1231 Dijon France

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

Unit of Infections and Cancer Cancer Epidemiology Research Programme Institut Català d' Oncologia Barcelona Spain

University of California Davis California

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