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

The Myositis Genetics Consortium (MYOGEN), 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 & 16 others 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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

LanguageEnglish
Article number117
JournalArthritis Research and Therapy
Volume20
Issue number1
DOIs
StatusPublished - 8 Jun 2018

Fingerprint

Myositis
Dermatomyositis
Autoantibodies
HLA Antigens
Single Nucleotide Polymorphism
Genetic Background
transcriptional intermediary factor 1
Ultraviolet Rays
Healthy Volunteers
Transcription Factors
Logistic Models
Alleles

Keywords

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

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis. / The Myositis Genetics Consortium (MYOGEN).

In: Arthritis Research and Therapy, Vol. 20, No. 1, 117, 08.06.2018.

Research output: Contribution to journalArticle

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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 = "{The Myositis Genetics Consortium (MYOGEN)} and 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.}",
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T1 - Genetic background may contribute to the latitude-dependent prevalence of dermatomyositis and anti-TIF1-γ autoantibodies in adult patients with myositis

AU - The Myositis Genetics Consortium (MYOGEN)

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.

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

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DO - 10.1186/s13075-018-1617-9

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