BACKGROUND: Based on epidemiological commonalities, multiple sclerosis (MS) and Hodgkin lymphoma (HL), two clinically distinct conditions, have long been suspected to be aetiologically related. MS and HL occur in roughly the same age groups, both are associated with Epstein-Barr virus infection and ultraviolet (UV) light exposure, and they cluster mutually in families (though not in individuals). We speculated if in addition to sharing environmental risk factors, MS and HL were also genetically related. Using data from genome-wide association studies (GWAS) of 1816 HL patients, 9772 MS patients and 25 255 controls, we therefore investigated the genetic overlap between the two diseases. METHODS: From among a common denominator of 404 K single nucleotide polymorphisms (SNPs) studied, we identified SNPs and human leukocyte antigen (HLA) alleles independently associated with both diseases. Next, we assessed the cumulative genome-wide effect of MS-associated SNPs on HL and of HL-associated SNPs on MS. To provide an interpretational frame of reference, we used data from published GWAS to create a genetic network of diseases within which we analysed proximity of HL and MS to autoimmune diseases and haematological and non-haematological malignancies. RESULTS: SNP analyses revealed genome-wide overlap between HL and MS, most prominently in the HLA region. Polygenic HL risk scores explained 4.44% of HL risk (Nagelkerke R(2)), but also 2.36% of MS risk. Conversely, polygenic MS risk scores explained 8.08% of MS risk and 1.94% of HL risk. In the genetic disease network, HL was closer to autoimmune diseases than to solid cancers. CONCLUSIONS: HL displays considerable genetic overlap with MS and other autoimmune diseases.

Cancer Prevention Institute of California Fremont CA USA

Catalan Institute of Oncology L'Hospitalet de Llobregat Catalonia Spain

Center for Neuroengineering and Thereapeutics at the University of Pennsylvania Philadelphia PA USA University of California San Francisco CA USA

Centre Hospitalier Universitaire de Dijon Dijon France

City of Hope National Medical Center Duarte CA USA

International Agency for Research on Cancer Lyon France

Karolinska Institute Stockholm Sweden

Masaryk Memorial Cancer Institute Brno Czech Republic

MRC University of Glasgow Centre for Virus Research Glasgow UK

Statens Serum Institut Copenhagen S Denmark

University College Dublin Dublin Ireland

University Medical Center Freiburg Freiburg Germany

University Medical Center Groningen The Netherlands

University of Cagliari Cagliari Sardinia Italy

University of California San Francisco CA USA

University of Chicago Chicago IL USA

University of Southern California Los Angeles CA USA

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Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes

HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes