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

Year: 2016

Type: review

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 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.

Source: International Journal of Epidemiology

DOI: 10.1093/ije/dyv364

Institutions: University of California, San Francisco, University of Pennsylvania, University of Southern California, University Medical Center Groningen, Cancer Prevention Institute of California, Karolinska Institutet, Institut Català d'Oncologia, University Medical Center Freiburg, University of Cagliari, CHU Dijon Bourgogne, Masaryk Memorial Cancer Institute, University College Dublin, Centre international de recherche sur le cancer, City Of Hope National Medical Center, Statens Serum Institut, University of Chicago, MRC University of Glasgow Centre for Virus Research

Language: English

Topic: Multiple Sclerosis Research Studies

Subfield: Pathology and Forensic Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,514

Funders: National Science Foundation, U.S. Department of Defense, U.S. Department of Health and Human Services, World Health Organization, University of Pennsylvania, Wellcome Trust, American Lebanese Syrian Associated Charities, Lundbeckfonden, Dansk Kræftforsknings Fond, H. Lundbeck A/S, National Institutes of Health, U.S. Army, Medical Research Council, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, Medical Research and Materiel Command

OpenAlex ID: W2310337733