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

Khankhanian, P. et al. (2016) Meta-analysis of genome-wide association studies reveals genetic overlap between Hodgkin lymphoma and multiple sclerosis. International Journal of Epidemiology, 45(3), pp. 728-740. (doi:10.1093/ije/dyv364) (PMID:26971321) (PMCID:PMC5005944)

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Abstract

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 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.

Item Type:Articles
Additional Information:Funding for this project was obtained from the Nordic Cancer Union (16-02-D to H.H.), the Lundbeck Foundation (R19-A2364 to H.H.), the Danish Cancer Research Foundation (41-08 to H.H.), the National Institutes of Health (CA110836 to W.C.; HD0433871, CA129045, and CA40046 to K.O.; CA55727 to L.L.R.; CA58839 to T.M.M.), the United States Army Medical Research and Materiel Command (Department of Defense PR054600 to W.C.), the American Cancer Society Illinois Division (to K.O.), the American Lebanese Syrian Associated Charities (to L.L.R.), the Leukemia & Lymphoma Society (TR6137-07 to W.C.), the Cancer Research Foundation (to K.O.), the National Cancer Institute Surveillance Epidemiology and End Results Population-based Registry Program at the National Institutes of Health in the Department of Health and Human Services (R01-NS-026799 to J.R.O., N01-PC-35139 to W.C. and N01-PC-35136 to the Cancer Prevention Institute of California), the National Cancer Institute (263-MQ-417755 to S.L.G.), the Leukemia Lymphoma Research and Kay Kendall Leukemia fund (grant 12022 to R.F.J.), the California Cancer Registry and the Dutch Cancer Society (KWF grants RUG 2009-4313 and RUG 2014-6698 to A.v.d.B.), the National Science Foundation (Graduate Research Fellowship Grant 1144247 to D.S.H.) and the Center for Neuroengineering and Therapeutics at the University of Pennsylvania (P.K.).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jarrett, Professor Ruth
Authors: Khankhanian, P., Cozen, W., Himmelstein, D. S., Madireddy, L., Din, L., van den Berg, A., Matsushita, T., Glaser, S. L., More, J. M., Smedby, K. E., Baranzini, S. E., Mack, T. M., Lizee, A., de Sanjose, S., Gourraud, P.-A., Nieters, A., Hauser, S. L., Cocco, P., Maynadie, M., Foretova, L., Staines, A., Delahaye-Sourdeix, M., Li, D., Bhatia, S., Melbye, M., Onel, K., Jarrett, R., McKay, J. D., Oksenberg, J. R., and Hjalgrim, H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:International Journal of Epidemiology
Publisher:Oxford University Press
ISSN:0300-5771
ISSN (Online):1464-3685
Published Online:12 March 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in International Journal of Epidemiology 45(3): 728-740
Publisher Policy:Reproduced under a Creative Commons License

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