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Genet Epidemiol. 2019 Aug 13. doi: 10.1002/gepi.22242. [Epub ahead of print]

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.

Author information

1
College of Medicine, California Northstate University, Elk Grove, California.
2
Center for Neuroengineering and Therapeutics, Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
3
Division of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Solna, Sweden.
4
Faculty of Medicine, McGill University, Montreal, Canada.
5
Clinical Epidemiology, McGill University Health Centre, Research Institute, Montreal, Canada.
6
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
7
School of Medicine, Emory University, Atlanta, Georgia.
8
Centre of Chronic Immunodeficiency, University Medical Centre Freiburg, Freiburg im Breisgau, Germany.
9
Department of Population Sciences, City of Hope and the Beckman Research Institute, Duarte, California.
10
International Agency for Research on Cancer, Lyon, France.
11
Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Sardinia, Italy.
12
The University of Burgundy-Franche-Comté and CHU Dijon Bourgogne, Registre des Hémopathies Malignes de Côte d'Or, INSERM U1231, Dijon, France.
13
Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
14
School of Nursing and Human Science, Dublin City University, Dublin, Ireland.
15
Norris Comprehensive Cancer Center and Hospital, University of Southern California, Los Angeles, California.
16
Reproductive Health Global Program PATH, School of Public Health, University of Washington, Seattle, Washington, USA.
17
Unit of Infections and Cancer, Cancer Epidemiology Research Programme, Institut Català d' Oncologia, (IDIBELL), Barcelona, Spain.
18
Centro de Investigación Biomédica en Red, Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
19
Department of Medical and Molecular Genetics, King's College London, London, England.
20
Division of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
21
Center of Research in Epidemiology and Statistics, Sorbonne (CRESS), Epidemiology of Childhood and Adolescent Cancer Group, INSERM, Paris, France.
22
Registre des Hémopathies Malignes de la Gironde, Institut Bergonie, Bordeaux, France.
23
Department of Obstetrics and Gynecology, Department of Population Health, Department of Environmental Medicine, NYU School of Medicine, New York, New York.
24
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada.
25
Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, Canada.
26
Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
27
Department of Immunology, Genetics, and Pathology, Uppsala Universitet, Uppsala, Sweden.
28
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
29
Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
30
Memorial Sloan Kettering Cancer Center, New York, New York.
31
Centre for Big Data Research in Health, University of New South Wales, Kensington, Australia.
32
Lymphoid Malignancies Unit, Henri Mondor Hospital, University Paris-Est Créteil (UPEC), Paris, France.
33
Medicina Traslazionale, Università del Piemonte Orientale, Vercelli, Italy.
34
Department of Preventive Medicine, University of Southern California, Los Angeles, Califonia.
35
Centre de Recherche en Cancerologie de Lyon, Lyon, France.
36
Department of Health Sciences, University of York, York, England.
37
Department of Medicine, Universita degli Studi di Perugia, Perugia, Italy.
38
Hematology Department, Centre Hospitalier Universitaire de Lyon, Lyon, France.
39
Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.
40
Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Australia.
41
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
42
Clinical Effectiveness Research Group, Institute of Health, University of Oslo, Oslo, Norway.
43
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
44
Department of Environmental Epidemiology of Cancers, INSERM, Paris, France.
45
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
46
Population Oncology, British Columbia Cancer Agency, Vancouver, Canada.
47
School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
48
Department of Internal Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake, Utah.
49
Department of Pediatrics, University of Chicago, Chicago, Illinois.
50
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
51
Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York.
52
Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.
53
Bill Lyons Informatics Centre, UCL Cancer Institute, University College London Cancer Institute, London, England.
54
Environmental and Occupational Epidemiology Branch, Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research Prevention and Clinical Network (ISPRO), Florence, Florence, Italy.
55
Department of Epidemiology Research, Statens Serum Institut, København, Denmark.
56
School of Medicine, Stanford University, Stanford, California.
57
School of Biomedical Sciences, University of Calgary, Calgary, Canada.
58
Division of Cancer Biology, National Cancer Institute, Bethesda, Maryland.
59
Department of Clinical Pathology, Genetic Epidemiology Laboratory, University of Melbourne, Melbourne, Australia.
60
Precision Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia.
61
California State University, Sacramento, Califonia.
62
Department of Biomedical Informatics, University of Utah, Salt Lake, Utah.
63
Clinical School, Concord Hospital, University of Sydney, Sydney, Australia.
64
Centre for Epidemiology and Intelligence, Cancer Council Australia, Melbourne, Australia.
65
Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
66
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
67
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
68
School of Public Health, Imperial College London, London, England.
69
Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
70
Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan.
71
Division of Environmental Epidemiology, Institute for Risk Assessment Science, Utrecht University, Utrecht, Netherlands.
72
Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
73
Cancer Epidemiology Unit, University of Oxford, Oxford, England.
74
School of Public Health, Brown University, Providence, Rhode Island.
75
Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut.
76
University of California, Davis, California.
77
 Department of Neurology, University of California, San Francisco, California.
78
Centre de Recherche en Transplantation et Immunologie, Université de Nantes, Centre Hospitalier Universitaire (CHU, INSERM), Nantes, France.
79
Santé Publique, Clinique des Données, Centre Hospitalier Universitaire (CHU) de Nantes, INSERM, Nantes, France.
80
Departments of Preventive Medicine and Pathology, Norris Comprehensive Cancer Center and Hospital, University of Southern California, Los Angeles, California.

Abstract

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.

KEYWORDS:

autoimmune disease; genome-wide association study; meta-analysis; non-Hodgkin lymphoma

PMID:
31407831
DOI:
10.1002/gepi.22242

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