title: Meta-analysis of genome-wide association studies reveals genetic overlap between Hodgkin lymphoma and multiple sclerosis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  HL displays considerable genetic overlap with MS and other autoimmune diseases.
authors.affiliation: Center for Neuroengineering and Thereapeutics at the University of Pennsylvania, Philadelphia, PA, USA University of California, San Francisco, CA, USA.
authors.forename: Pouya
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authors.lastname: Khankhanian
authors.affiliation: University of Southern California, Los Angeles, CA, USA.
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authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Himmelstein
authors.affiliation: University of California, San Francisco, CA, USA.
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authors.affiliation: University of California, San Francisco, CA, USA.
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authors.affiliation: University Medical Center, Groningen, The Netherlands.
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authors.affiliation: University of California, San Francisco, CA, USA.
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authors.affiliation: University of California, San Francisco, CA, USA.
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authors.affiliation: Karolinska Institute, Stockholm, Sweden.
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authors.lastname: Smedby
authors.affiliation: University of California, San Francisco, CA, USA.
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authors.affiliation: University of Southern California, Los Angeles, CA, USA.
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authors.affiliation: University of California, San Francisco, CA, USA.
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authors.affiliation: Catalan Institute of Oncology, L'Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Silvia
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authors.lastname: de Sanjosé
authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: Pierre-Antoine
authors.initials: PA
authors.lastname: Gourraud
authors.affiliation: University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nieters
authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hauser
authors.affiliation: University of Cagliari, Cagliari, Sardinia, Italy.
authors.forename: Pierluigi
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authors.lastname: Cocco
authors.affiliation: Centre Hospitalier Universitaire de Dijon, Dijon, France.
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authors.affiliation: Masaryk Memorial Cancer Institute, Brno, Czech Republic.
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authors.lastname: Foretová
authors.affiliation: University College Dublin, Dublin, Ireland.
authors.forename: Anthony
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authors.lastname: Staines
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Manon
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authors.lastname: Delahaye-Sourdeix
authors.affiliation: University of Southern California, Los Angeles, CA, USA.
authors.forename: Dalin
authors.initials: D
authors.lastname: Li
authors.affiliation: City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: Smita
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authors.lastname: Bhatia
authors.affiliation: Statens Serum Institut, Copenhagen S, Denmark.
authors.forename: Mads
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authors.lastname: Melbye
authors.affiliation: University of Chicago, Chicago, IL, USA.
authors.forename: Kenan
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authors.lastname: Onel
authors.affiliation: MRC, University of Glasgow Centre for Virus Research, Glasgow, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Jarrett
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: James D
authors.initials: JD
authors.lastname: McKay
authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Oksenberg
authors.affiliation: Statens Serum Institut, Copenhagen S, Denmark HHJ@ssi.dk.
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mesh_terms: D005260:Female; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006689:Hodgkin Disease / Q000235:genetics*; D006801:Humans; D016014:Linear Models; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide