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

Pouya Khankhanian, Wendy Cozen, Daniel S. Himmelstein, Lohith Madireddy, Lennox Din, Anke van den Berg, Takuya Matsushita, Sally L. Glaser, Jayaji M. Moré, Karin E. Smedby, Sergio E. Baranzini, Thomas M. Mack, Antoine Lizée, Silvia de Sanjosé, Pierre Antoine Gourraud, Alexandra Nieters, Stephen L. Hauser, Pierluigi Cocco, Marc Maynadié, Lenka Foretová & 10 others Anthony Staines, Manon Delahaye-Sourdeix, Dalin Li, Smita Bhatia, Mads Melbye, Kenan Onel, Ruth Jarrett, James D. McKay, Jorge R. Oksenberg, Henrik Hjalgrim

    研究成果: ジャーナルへの寄稿記事

    11 引用 (Scopus)

    抄録

    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.

    元の言語英語
    ページ(範囲)728-740
    ページ数13
    ジャーナルInternational Journal of Epidemiology
    45
    発行部数3
    DOI
    出版物ステータス出版済み - 1 1 2016

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    Genome-Wide Association Study
    Hodgkin Disease
    Multiple Sclerosis
    Meta-Analysis
    Single Nucleotide Polymorphism
    Autoimmune Diseases
    Inborn Genetic Diseases
    HLA Antigens
    Genome
    Epstein-Barr Virus Infections
    Ultraviolet Rays
    Neoplasms
    Age Groups
    Alleles

    All Science Journal Classification (ASJC) codes

    • Epidemiology

    これを引用

    Khankhanian, P., Cozen, W., Himmelstein, D. S., Madireddy, L., Din, L., Berg, A. V. D., ... Hjalgrim, H. (2016). Meta-analysis of genome-wide association studies reveals genetic overlap between hodgkin lymphoma and multiple sclerosis. International Journal of Epidemiology, 45(3), 728-740. https://doi.org/10.1093/IJE/DYV364

    Meta-analysis of genome-wide association studies reveals genetic overlap between hodgkin lymphoma and multiple sclerosis. / Khankhanian, Pouya; Cozen, Wendy; Himmelstein, Daniel S.; Madireddy, Lohith; Din, Lennox; Berg, Anke van den; Matsushita, Takuya; Glaser, Sally L.; Moré, Jayaji M.; Smedby, Karin E.; Baranzini, Sergio E.; Mack, Thomas M.; Lizée, Antoine; Sanjosé, Silvia de; Gourraud, Pierre Antoine; Nieters, Alexandra; Hauser, Stephen L.; Cocco, Pierluigi; Maynadié, Marc; Foretová, Lenka; Staines, Anthony; Delahaye-Sourdeix, Manon; Li, Dalin; Bhatia, Smita; Melbye, Mads; Onel, Kenan; Jarrett, Ruth; McKay, James D.; Oksenberg, Jorge R.; Hjalgrim, Henrik.

    :: International Journal of Epidemiology, 巻 45, 番号 3, 01.01.2016, p. 728-740.

    研究成果: ジャーナルへの寄稿記事

    Khankhanian, P, Cozen, W, Himmelstein, DS, Madireddy, L, Din, L, Berg, AVD, Matsushita, T, Glaser, SL, Moré, JM, Smedby, KE, Baranzini, SE, Mack, TM, Lizée, A, Sanjosé, SD, Gourraud, PA, Nieters, A, Hauser, SL, Cocco, P, Maynadié, M, Foretová, L, Staines, A, Delahaye-Sourdeix, M, Li, D, Bhatia, S, Melbye, M, Onel, K, Jarrett, R, McKay, JD, Oksenberg, JR & Hjalgrim, H 2016, 'Meta-analysis of genome-wide association studies reveals genetic overlap between hodgkin lymphoma and multiple sclerosis', International Journal of Epidemiology, 巻. 45, 番号 3, pp. 728-740. https://doi.org/10.1093/IJE/DYV364
    Khankhanian, Pouya ; Cozen, Wendy ; Himmelstein, Daniel S. ; Madireddy, Lohith ; Din, Lennox ; Berg, Anke van den ; Matsushita, Takuya ; Glaser, Sally L. ; Moré, Jayaji M. ; Smedby, Karin E. ; Baranzini, Sergio E. ; Mack, Thomas M. ; Lizée, Antoine ; Sanjosé, Silvia de ; Gourraud, Pierre Antoine ; Nieters, Alexandra ; Hauser, Stephen L. ; Cocco, Pierluigi ; Maynadié, Marc ; Foretová, Lenka ; Staines, Anthony ; Delahaye-Sourdeix, Manon ; Li, Dalin ; Bhatia, Smita ; Melbye, Mads ; Onel, Kenan ; Jarrett, Ruth ; McKay, James D. ; Oksenberg, Jorge R. ; Hjalgrim, Henrik. / Meta-analysis of genome-wide association studies reveals genetic overlap between hodgkin lymphoma and multiple sclerosis. :: International Journal of Epidemiology. 2016 ; 巻 45, 番号 3. pp. 728-740.
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    title = "Meta-analysis of genome-wide association studies reveals genetic overlap between hodgkin lymphoma and multiple sclerosis",
    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, 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.",
    author = "Pouya Khankhanian and Wendy Cozen and Himmelstein, {Daniel S.} and Lohith Madireddy and Lennox Din and Berg, {Anke van den} and Takuya Matsushita and Glaser, {Sally L.} and Mor{\'e}, {Jayaji M.} and Smedby, {Karin E.} and Baranzini, {Sergio E.} and Mack, {Thomas M.} and Antoine Liz{\'e}e and Sanjos{\'e}, {Silvia de} and Gourraud, {Pierre Antoine} and Alexandra Nieters and Hauser, {Stephen L.} and Pierluigi Cocco and Marc Maynadi{\'e} and Lenka Foretov{\'a} and Anthony Staines and Manon Delahaye-Sourdeix and Dalin Li and Smita Bhatia and Mads Melbye and Kenan Onel and Ruth Jarrett and McKay, {James D.} and Oksenberg, {Jorge R.} and Henrik Hjalgrim",
    year = "2016",
    month = "1",
    day = "1",
    doi = "10.1093/IJE/DYV364",
    language = "English",
    volume = "45",
    pages = "728--740",
    journal = "International Journal of Epidemiology",
    issn = "0300-5771",
    publisher = "Oxford University Press",
    number = "3",

    }

    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

    PY - 2016/1/1

    Y1 - 2016/1/1

    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.

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    U2 - 10.1093/IJE/DYV364

    DO - 10.1093/IJE/DYV364

    M3 - Article

    VL - 45

    SP - 728

    EP - 740

    JO - International Journal of Epidemiology

    JF - International Journal of Epidemiology

    SN - 0300-5771

    IS - 3

    ER -