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Int J Epidemiol. 2016 Jun;45(3):728-40. doi: 10.1093/ije/dyv364. Epub 2016 Mar 12.

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

Author information

1
Center for Neuroengineering and Thereapeutics at the University of Pennsylvania, Philadelphia, PA, USA University of California, San Francisco, CA, USA.
2
University of Southern California, Los Angeles, CA, USA.
3
University of California, San Francisco, CA, USA.
4
University Medical Center, Groningen, The Netherlands.
5
Cancer Prevention Institute of California, Fremont, CA, USA.
6
Karolinska Institute, Stockholm, Sweden.
7
Catalan Institute of Oncology, L'Hospitalet de Llobregat, Catalonia, Spain.
8
University Medical Center Freiburg, Freiburg, Germany.
9
University of Cagliari, Cagliari, Sardinia, Italy.
10
Centre Hospitalier Universitaire de Dijon, Dijon, France.
11
Masaryk Memorial Cancer Institute, Brno, Czech Republic.
12
University College Dublin, Dublin, Ireland.
13
International Agency for Research on Cancer, Lyon, France.
14
City of Hope National Medical Center, Duarte, CA, USA.
15
Statens Serum Institut, Copenhagen S, Denmark.
16
University of Chicago, Chicago, IL, USA.
17
MRC, University of Glasgow Centre for Virus Research, Glasgow, UK.
18
Statens Serum Institut, Copenhagen S, Denmark HHJ@ssi.dk.

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.

PMID:
26971321
PMCID:
PMC5005944
DOI:
10.1093/ije/dyv364
[Indexed for MEDLINE]
Free PMC Article

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