Meta-analysis of genome-wide association studies reveals genetic overlap between hodgkin lymphoma and multiple sclerosis

Pouya Khankhanian, Wendy Cozen, Daniel S. Himmelstein, Lohith Madireddy, Lennox Din, Anke van den Berg, Takuya Matsushita, Sally L. Glaser, Jayaji M. Moré, Karin E. Smedby, Sergio E. Baranzini, Thomas M. Mack, Antoine Lizée, Silvia de Sanjosé, Pierre Antoine Gourraud, Alexandra Nieters, Stephen L. Hauser, Pierluigi Cocco, Marc Maynadié, Lenka ForetováAnthony Staines, Manon Delahaye-Sourdeix, Dalin Li, Smita Bhatia, Mads Melbye, Kenan Onel, Ruth Jarrett, James D. McKay, Jorge R. Oksenberg, Henrik Hjalgrim

    Research output: Contribution to journalArticlepeer-review

    20 Citations (Scopus)


    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, 9772MS 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 R2), 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.

    Original languageEnglish
    Pages (from-to)728-740
    Number of pages13
    JournalInternational Journal of Epidemiology
    Issue number3
    Publication statusPublished - 2016

    All Science Journal Classification (ASJC) codes

    • Epidemiology


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