Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis

Joanna E. Parkes; Simon Rothwell; Alexander Oldroyd; Hector Chinoy; Janine A. Lamb; Ingrid E. Lundberg; Frederick W. Miller; Robert G. Cooper; William E. Ollier; Peter K. Gregersen; Jiri Vencovsky; Katalin Danko; Vidya Limaye; Albert Selva-O'Callaghan; Pedro M. Machado; Michael G. Hanna; Hazel Platt; Øyvind Molberg; Olivier Benveniste; Timothy Radstake; Jan De Bleecker; Boel De Paepe; Britta Maurer; Leonid Padyukov; Terrance P. O'Hanlon; Lucy R. Wedderburn; Christopher Denton; Herman Mann; David Hilton-Jones; Patrick Kiely; Paul H. Plotz; Mark Gourley; Galina Marder; Neil J. McHugh; Zoe E. Betteridge

doi:10.1186/s13075-018-1617-9

Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis

Joanna E. Parkes^*, Simon Rothwell, Alexander Oldroyd, Hector Chinoy, Janine A. Lamb, Ingrid E. Lundberg, Frederick W. Miller, Robert G. Cooper, William E. Ollier, Peter K. Gregersen, Jiri Vencovsky, Katalin Danko, Vidya Limaye, Albert Selva-O'Callaghan, Pedro M. Machado, Michael G. Hanna, Hazel Platt, Øyvind Molberg, Olivier Benveniste, Timothy RadstakeJan De Bleecker, Boel De Paepe, Britta Maurer, Leonid Padyukov, Terrance P. O'Hanlon, Lucy R. Wedderburn, Christopher Denton, Herman Mann, David Hilton-Jones, Patrick Kiely, Paul H. Plotz, Mark Gourley, Galina Marder, Neil J. McHugh, Zoe E. Betteridge,

^*Corresponding author for this work

Infection & Immunity

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: The prevalence of dermatomyositis (DM) versus DM and polymyositis (PM) combined has been shown to be negatively associated with latitude. This observation has been attributed to increasing exposure to ultraviolet (UV) light towards the equator. In this study, we investigated whether differing genetic background in populations could contribute to this distribution of DM. Methods: Case data derived from the MYOGEN (Myositis Genetics Consortium) Immunochip study (n = 1769) were used to model the association of DM prevalence and DM-specific autoantibodies with latitude. Control data (n = 9911) were used to model the relationship of human leucocyte antigen (HLA) associated with DM autoantibodies and DM or PM single-nucleotide polymorphisms (suggestive significance in the Immunochip project, P < 2.25 × 10^{- 5}) in healthy control subjects with latitude. All variables were analysed against latitude using ordered logistic regression, adjusted for sex. Results: The prevalence of DM, as a proportion of DM and PM combined, and the presence of anti-transcription intermediary factor 1 (anti-TIF1-γ) autoantibodies were both significantly negatively associated with latitude (OR 0.96, 95% CI 0.95-0.98, P < 0.001; and OR 0.95, 95% CI 0.92-0.99, P = 0.004, respectively). HLA alleles significantly associated with anti-Mi-2 and anti-TIF1-γ autoantibodies also were strongly negatively associated with latitude (OR 0.97, 95% CI 0.96-0.98, P < 0.001 and OR 0.98, 95% CI 0.97-0.99, P < 0.001, respectively). The frequency of five PM- or DM-associated SNPs showed a significant association with latitude (P < 0.05), and the direction of four of these associations was consistent with the latitude associations of the clinical phenotypes. Conclusions: These results lend some support to the hypothesis that genetic background, in addition to UV exposure, may contribute to the distribution of DM.

Original language	English
Article number	117
Journal	Arthritis Research and Therapy
Volume	20
Issue number	1
DOIs	https://doi.org/10.1186/s13075-018-1617-9
Publication status	Published - 8 Jun 2018

Keywords

Anti-Mi-2
Anti-TIF1-γ
Dermatomyositis
Latitude
Polymyositis
Ultraviolet light

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Parkes, J. E., Rothwell, S., Oldroyd, A., Chinoy, H., Lamb, J. A., Lundberg, I. E., Miller, F. W., Cooper, R. G., Ollier, W. E., Gregersen, P. K., Vencovsky, J., Danko, K., Limaye, V., Selva-O'Callaghan, A., Machado, P. M., Hanna, M. G., Platt, H., Molberg, Ø., Benveniste, O. (2018). Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis. Arthritis Research and Therapy, 20(1), Article 117. https://doi.org/10.1186/s13075-018-1617-9

@article{ccaee7e7b068402e85c99a9cc9e02b4e,

title = "Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis",

abstract = "Background: The prevalence of dermatomyositis (DM) versus DM and polymyositis (PM) combined has been shown to be negatively associated with latitude. This observation has been attributed to increasing exposure to ultraviolet (UV) light towards the equator. In this study, we investigated whether differing genetic background in populations could contribute to this distribution of DM. Methods: Case data derived from the MYOGEN (Myositis Genetics Consortium) Immunochip study (n = 1769) were used to model the association of DM prevalence and DM-specific autoantibodies with latitude. Control data (n = 9911) were used to model the relationship of human leucocyte antigen (HLA) associated with DM autoantibodies and DM or PM single-nucleotide polymorphisms (suggestive significance in the Immunochip project, P < 2.25 × 10- 5) in healthy control subjects with latitude. All variables were analysed against latitude using ordered logistic regression, adjusted for sex. Results: The prevalence of DM, as a proportion of DM and PM combined, and the presence of anti-transcription intermediary factor 1 (anti-TIF1-γ) autoantibodies were both significantly negatively associated with latitude (OR 0.96, 95% CI 0.95-0.98, P < 0.001; and OR 0.95, 95% CI 0.92-0.99, P = 0.004, respectively). HLA alleles significantly associated with anti-Mi-2 and anti-TIF1-γ autoantibodies also were strongly negatively associated with latitude (OR 0.97, 95% CI 0.96-0.98, P < 0.001 and OR 0.98, 95% CI 0.97-0.99, P < 0.001, respectively). The frequency of five PM- or DM-associated SNPs showed a significant association with latitude (P < 0.05), and the direction of four of these associations was consistent with the latitude associations of the clinical phenotypes. Conclusions: These results lend some support to the hypothesis that genetic background, in addition to UV exposure, may contribute to the distribution of DM.",

keywords = "Anti-Mi-2, Anti-TIF1-γ, Dermatomyositis, Latitude, Polymyositis, Ultraviolet light",

author = "Parkes, {Joanna E.} and Simon Rothwell and Alexander Oldroyd and Hector Chinoy and Lamb, {Janine A.} and Lundberg, {Ingrid E.} and Miller, {Frederick W.} and Cooper, {Robert G.} and Ollier, {William E.} and Gregersen, {Peter K.} and Jiri Vencovsky and Katalin Danko and Vidya Limaye and Albert Selva-O'Callaghan and Machado, {Pedro M.} and Hanna, {Michael G.} and Hazel Platt and {\O}yvind Molberg and Olivier Benveniste and Timothy Radstake and {De Bleecker}, Jan and {De Paepe}, Boel and Britta Maurer and Leonid Padyukov and O'Hanlon, {Terrance P.} and Wedderburn, {Lucy R.} and Christopher Denton and Herman Mann and David Hilton-Jones and Patrick Kiely and Plotz, {Paul H.} and Mark Gourley and Galina Marder and McHugh, {Neil J.} and Betteridge, {Zoe E.}",

note = "Funding Information: This study was supported by Myositis UK, Medical Research Council (MRC) UK grant MR/N003322/1; Arthritis Research UK (18474), Association Francaise Contre Les Myopathies (AFM), the European Union Sixth Framework Programme (project AutoCure; LSH-018661), the European Science Foundation (ESF) within the framework of the Research Networking Programme European Myositis Network (EUMYONET), the Swedish Research Council and the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, and the intramural research program of the National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health (NIH). The Czech cohort was supported by Project for Conceptual Development of Research Organization 00023728 from the Ministry of Health in the Czech Republic. JEP is supported by a University of Manchester alumni “Research Impact” doctoral studentship and president{\textquoteright}s doctoral scholar award. This report includes description of independent research supported by the National Institute for Health Research. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = jun,

day = "8",

doi = "10.1186/s13075-018-1617-9",

language = "English",

volume = "20",

journal = "Arthritis Research and Therapy",

issn = "1478-6354",

publisher = "BioMed Central",

number = "1",

}

Parkes, JE, Rothwell, S, Oldroyd, A, Chinoy, H, Lamb, JA, Lundberg, IE, Miller, FW, Cooper, RG, Ollier, WE, Gregersen, PK, Vencovsky, J, Danko, K, Limaye, V, Selva-O'Callaghan, A, Machado, PM, Hanna, MG, Platt, H, Molberg, Ø, Benveniste, O, Radstake, T, De Bleecker, J, De Paepe, B, Maurer, B, Padyukov, L, O'Hanlon, TP, Wedderburn, LR, Denton, C, Mann, H, Hilton-Jones, D, Kiely, P, Plotz, PH, Gourley, M, Marder, G, McHugh, NJ, Betteridge, ZE 2018, 'Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis', Arthritis Research and Therapy, vol. 20, no. 1, 117. https://doi.org/10.1186/s13075-018-1617-9

TY - JOUR

T1 - Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis

AU - Parkes, Joanna E.

AU - Rothwell, Simon

AU - Oldroyd, Alexander

AU - Chinoy, Hector

AU - Lamb, Janine A.

AU - Lundberg, Ingrid E.

AU - Miller, Frederick W.

AU - Cooper, Robert G.

AU - Ollier, William E.

AU - Gregersen, Peter K.

AU - Vencovsky, Jiri

AU - Danko, Katalin

AU - Limaye, Vidya

AU - Selva-O'Callaghan, Albert

AU - Machado, Pedro M.

AU - Hanna, Michael G.

AU - Platt, Hazel

AU - Molberg, Øyvind

AU - Benveniste, Olivier

AU - Radstake, Timothy

AU - De Bleecker, Jan

AU - De Paepe, Boel

AU - Maurer, Britta

AU - Padyukov, Leonid

AU - O'Hanlon, Terrance P.

AU - Wedderburn, Lucy R.

AU - Denton, Christopher

AU - Mann, Herman

AU - Hilton-Jones, David

AU - Kiely, Patrick

AU - Plotz, Paul H.

AU - Gourley, Mark

AU - Marder, Galina

AU - McHugh, Neil J.

AU - Betteridge, Zoe E.

N1 - Funding Information: This study was supported by Myositis UK, Medical Research Council (MRC) UK grant MR/N003322/1; Arthritis Research UK (18474), Association Francaise Contre Les Myopathies (AFM), the European Union Sixth Framework Programme (project AutoCure; LSH-018661), the European Science Foundation (ESF) within the framework of the Research Networking Programme European Myositis Network (EUMYONET), the Swedish Research Council and the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, and the intramural research program of the National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health (NIH). The Czech cohort was supported by Project for Conceptual Development of Research Organization 00023728 from the Ministry of Health in the Czech Republic. JEP is supported by a University of Manchester alumni “Research Impact” doctoral studentship and president’s doctoral scholar award. This report includes description of independent research supported by the National Institute for Health Research. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. Publisher Copyright: © 2018 The Author(s).

PY - 2018/6/8

Y1 - 2018/6/8

N2 - Background: The prevalence of dermatomyositis (DM) versus DM and polymyositis (PM) combined has been shown to be negatively associated with latitude. This observation has been attributed to increasing exposure to ultraviolet (UV) light towards the equator. In this study, we investigated whether differing genetic background in populations could contribute to this distribution of DM. Methods: Case data derived from the MYOGEN (Myositis Genetics Consortium) Immunochip study (n = 1769) were used to model the association of DM prevalence and DM-specific autoantibodies with latitude. Control data (n = 9911) were used to model the relationship of human leucocyte antigen (HLA) associated with DM autoantibodies and DM or PM single-nucleotide polymorphisms (suggestive significance in the Immunochip project, P < 2.25 × 10- 5) in healthy control subjects with latitude. All variables were analysed against latitude using ordered logistic regression, adjusted for sex. Results: The prevalence of DM, as a proportion of DM and PM combined, and the presence of anti-transcription intermediary factor 1 (anti-TIF1-γ) autoantibodies were both significantly negatively associated with latitude (OR 0.96, 95% CI 0.95-0.98, P < 0.001; and OR 0.95, 95% CI 0.92-0.99, P = 0.004, respectively). HLA alleles significantly associated with anti-Mi-2 and anti-TIF1-γ autoantibodies also were strongly negatively associated with latitude (OR 0.97, 95% CI 0.96-0.98, P < 0.001 and OR 0.98, 95% CI 0.97-0.99, P < 0.001, respectively). The frequency of five PM- or DM-associated SNPs showed a significant association with latitude (P < 0.05), and the direction of four of these associations was consistent with the latitude associations of the clinical phenotypes. Conclusions: These results lend some support to the hypothesis that genetic background, in addition to UV exposure, may contribute to the distribution of DM.

AB - Background: The prevalence of dermatomyositis (DM) versus DM and polymyositis (PM) combined has been shown to be negatively associated with latitude. This observation has been attributed to increasing exposure to ultraviolet (UV) light towards the equator. In this study, we investigated whether differing genetic background in populations could contribute to this distribution of DM. Methods: Case data derived from the MYOGEN (Myositis Genetics Consortium) Immunochip study (n = 1769) were used to model the association of DM prevalence and DM-specific autoantibodies with latitude. Control data (n = 9911) were used to model the relationship of human leucocyte antigen (HLA) associated with DM autoantibodies and DM or PM single-nucleotide polymorphisms (suggestive significance in the Immunochip project, P < 2.25 × 10- 5) in healthy control subjects with latitude. All variables were analysed against latitude using ordered logistic regression, adjusted for sex. Results: The prevalence of DM, as a proportion of DM and PM combined, and the presence of anti-transcription intermediary factor 1 (anti-TIF1-γ) autoantibodies were both significantly negatively associated with latitude (OR 0.96, 95% CI 0.95-0.98, P < 0.001; and OR 0.95, 95% CI 0.92-0.99, P = 0.004, respectively). HLA alleles significantly associated with anti-Mi-2 and anti-TIF1-γ autoantibodies also were strongly negatively associated with latitude (OR 0.97, 95% CI 0.96-0.98, P < 0.001 and OR 0.98, 95% CI 0.97-0.99, P < 0.001, respectively). The frequency of five PM- or DM-associated SNPs showed a significant association with latitude (P < 0.05), and the direction of four of these associations was consistent with the latitude associations of the clinical phenotypes. Conclusions: These results lend some support to the hypothesis that genetic background, in addition to UV exposure, may contribute to the distribution of DM.

KW - Anti-Mi-2

KW - Anti-TIF1-γ

KW - Dermatomyositis

KW - Latitude

KW - Polymyositis

KW - Ultraviolet light

UR - http://www.scopus.com/inward/record.url?scp=85048288877&partnerID=8YFLogxK

U2 - 10.1186/s13075-018-1617-9

DO - 10.1186/s13075-018-1617-9

M3 - Article

C2 - 29884237

AN - SCOPUS:85048288877

SN - 1478-6354

VL - 20

JO - Arthritis Research and Therapy

JF - Arthritis Research and Therapy

IS - 1

M1 - 117

ER -

Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis

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