TY - JOUR
T1 - Meta-analysis of genome-wide association studies reveals genetic overlap between hodgkin lymphoma and multiple sclerosis
AU - Khankhanian, Pouya
AU - Cozen, Wendy
AU - Himmelstein, Daniel S.
AU - Madireddy, Lohith
AU - Din, Lennox
AU - Berg, Anke van den
AU - Matsushita, Takuya
AU - Glaser, Sally L.
AU - Moré, Jayaji M.
AU - Smedby, Karin E.
AU - Baranzini, Sergio E.
AU - Mack, Thomas M.
AU - Lizée, Antoine
AU - Sanjosé, Silvia de
AU - Gourraud, Pierre Antoine
AU - Nieters, Alexandra
AU - Hauser, Stephen L.
AU - Cocco, Pierluigi
AU - Maynadié, Marc
AU - Foretová, Lenka
AU - Staines, Anthony
AU - Delahaye-Sourdeix, Manon
AU - Li, Dalin
AU - Bhatia, Smita
AU - Melbye, Mads
AU - Onel, Kenan
AU - Jarrett, Ruth
AU - McKay, James D.
AU - Oksenberg, Jorge R.
AU - Hjalgrim, Henrik
N1 - Publisher Copyright:
© The Author 2016.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85032888825
U2 - 10.1093/IJE/DYV364
DO - 10.1093/IJE/DYV364
M3 - Article
C2 - 26971321
AN - SCOPUS:85032888825
SN - 0300-5771
VL - 45
SP - 728
EP - 740
JO - International Journal of Epidemiology
JF - International Journal of Epidemiology
IS - 3
ER -