PMID- 26971321
OWN - NLM
STAT- MEDLINE
DCOM- 20180104
LR  - 20240324
IS  - 1464-3685 (Electronic)
IS  - 0300-5771 (Print)
IS  - 0300-5771 (Linking)
VI  - 45
IP  - 3
DP  - 2016 Jun
TI  - Meta-analysis of genome-wide association studies reveals genetic overlap between 
      Hodgkin lymphoma and multiple sclerosis.
PG  - 728-40
LID - 10.1093/ije/dyv364 [doi]
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, 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.
CI  - (c) The Author 2016. Published by Oxford University Press on behalf of the 
      International Epidemiological Association.
FAU - Khankhanian, Pouya
AU  - Khankhanian P
AD  - Center for Neuroengineering and Thereapeutics at the University of Pennsylvania, 
      Philadelphia, PA, USA University of California, San Francisco, CA, USA.
FAU - Cozen, Wendy
AU  - Cozen W
AD  - University of Southern California, Los Angeles, CA, USA.
FAU - Himmelstein, Daniel S
AU  - Himmelstein DS
AD  - University of California, San Francisco, CA, USA.
FAU - Madireddy, Lohith
AU  - Madireddy L
AD  - University of California, San Francisco, CA, USA.
FAU - Din, Lennox
AU  - Din L
AD  - University of California, San Francisco, CA, USA.
FAU - van den Berg, Anke
AU  - van den Berg A
AD  - University Medical Center, Groningen, The Netherlands.
FAU - Matsushita, Takuya
AU  - Matsushita T
AD  - University of California, San Francisco, CA, USA.
FAU - Glaser, Sally L
AU  - Glaser SL
AD  - Cancer Prevention Institute of California, Fremont, CA, USA.
FAU - More, Jayaji M
AU  - More JM
AD  - University of California, San Francisco, CA, USA.
FAU - Smedby, Karin E
AU  - Smedby KE
AD  - Karolinska Institute, Stockholm, Sweden.
FAU - Baranzini, Sergio E
AU  - Baranzini SE
AD  - University of California, San Francisco, CA, USA.
FAU - Mack, Thomas M
AU  - Mack TM
AD  - University of Southern California, Los Angeles, CA, USA.
FAU - Lizee, Antoine
AU  - Lizee A
AD  - University of California, San Francisco, CA, USA.
FAU - de Sanjose, Silvia
AU  - de Sanjose S
AD  - Catalan Institute of Oncology, L'Hospitalet de Llobregat, Catalonia, Spain.
FAU - Gourraud, Pierre-Antoine
AU  - Gourraud PA
AD  - University of California, San Francisco, CA, USA.
FAU - Nieters, Alexandra
AU  - Nieters A
AD  - University Medical Center Freiburg, Freiburg, Germany.
FAU - Hauser, Stephen L
AU  - Hauser SL
AD  - University of California, San Francisco, CA, USA.
FAU - Cocco, Pierluigi
AU  - Cocco P
AD  - University of Cagliari, Cagliari, Sardinia, Italy.
FAU - Maynadie, Marc
AU  - Maynadie M
AD  - Centre Hospitalier Universitaire de Dijon, Dijon, France.
FAU - Foretova, Lenka
AU  - Foretova L
AD  - Masaryk Memorial Cancer Institute, Brno, Czech Republic.
FAU - Staines, Anthony
AU  - Staines A
AD  - University College Dublin, Dublin, Ireland.
FAU - Delahaye-Sourdeix, Manon
AU  - Delahaye-Sourdeix M
AD  - International Agency for Research on Cancer, Lyon, France.
FAU - Li, Dalin
AU  - Li D
AD  - University of Southern California, Los Angeles, CA, USA.
FAU - Bhatia, Smita
AU  - Bhatia S
AD  - City of Hope National Medical Center, Duarte, CA, USA.
FAU - Melbye, Mads
AU  - Melbye M
AD  - Statens Serum Institut, Copenhagen S, Denmark.
FAU - Onel, Kenan
AU  - Onel K
AD  - University of Chicago, Chicago, IL, USA.
FAU - Jarrett, Ruth
AU  - Jarrett R
AD  - MRC, University of Glasgow Centre for Virus Research, Glasgow, UK.
FAU - McKay, James D
AU  - McKay JD
AD  - International Agency for Research on Cancer, Lyon, France.
FAU - Oksenberg, Jorge R
AU  - Oksenberg JR
AD  - University of California, San Francisco, CA, USA.
FAU - Hjalgrim, Henrik
AU  - Hjalgrim H
AD  - Statens Serum Institut, Copenhagen S, Denmark HHJ@ssi.dk.
LA  - eng
GR  - U24 CA055727/CA/NCI NIH HHS/United States
GR  - T32 GM067547/GM/NIGMS NIH HHS/United States
GR  - R25 NS070680/NS/NINDS NIH HHS/United States
GR  - T32 EB009383/EB/NIBIB NIH HHS/United States
GR  - N01PC35136/CA/NCI NIH HHS/United States
GR  - N01PC35139/CA/NCI NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
GR  - R01 NS026799/NS/NINDS NIH HHS/United States
GR  - 001/WHO_/World Health Organization/International
GR  - MC_UU_12014/3/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20160312
PL  - England
TA  - Int J Epidemiol
JT  - International journal of epidemiology
JID - 7802871
SB  - IM
MH  - Female
MH  - Gene Regulatory Networks
MH  - Genetic Predisposition to Disease
MH  - *Genome-Wide Association Study
MH  - Hodgkin Disease/*genetics
MH  - Humans
MH  - Linear Models
MH  - Male
MH  - Multiple Sclerosis/*genetics
MH  - *Polymorphism, Single Nucleotide
PMC - PMC5005944
EDAT- 2016/03/14 06:00
MHDA- 2018/01/05 06:00
PMCR- 2016/03/12
CRDT- 2016/03/14 06:00
PHST- 2015/12/18 00:00 [accepted]
PHST- 2016/03/14 06:00 [entrez]
PHST- 2016/03/14 06:00 [pubmed]
PHST- 2018/01/05 06:00 [medline]
PHST- 2016/03/12 00:00 [pmc-release]
AID - dyv364 [pii]
AID - 10.1093/ije/dyv364 [pii]
AID - 10.1093/ije/dyv364 [doi]
PST - ppublish
SO  - Int J Epidemiol. 2016 Jun;45(3):728-40. doi: 10.1093/ije/dyv364. Epub 2016 Mar 
      12.