Skip to main content
Journal cover image

Identification of Novel Associations and Localization of Signals in Idiopathic Inflammatory Myopathies Using Genome-Wide Imputation.

Publication ,  Journal Article
Rothwell, S; Amos, CI; Miller, FW; Rider, LG; Lundberg, IE; Gregersen, PK; Vencovsky, J; McHugh, N; Limaye, V; Selva-O'Callaghan, A; Hanna, MG ...
Published in: Arthritis & rheumatology (Hoboken, N.J.)
June 2023

The idiopathic inflammatory myopathies (IIMs) are heterogeneous diseases thought to be initiated by immune activation in genetically predisposed individuals. We imputed variants from the ImmunoChip array using a large reference panel to fine-map associations and identify novel associations in IIM.We analyzed 2,565 Caucasian IIM patient samples collected through the Myositis Genetics Consortium (MYOGEN) and 10,260 ethnically matched control samples. We imputed 1,648,116 variants from the ImmunoChip array using the Haplotype Reference Consortium panel and conducted association analysis on IIM and clinical and serologic subgroups.The HLA locus was consistently the most significantly associated region. Four non-HLA regions reached genome-wide significance, SDK2 and LINC00924 (both novel) and STAT4 in the whole IIM cohort, with evidence of independent variants in STAT4, and NAB1 in the polymyositis (PM) subgroup. We also found suggestive evidence of association with loci previously associated with other autoimmune rheumatic diseases (TEC and LTBR). We identified more significant associations than those previously reported in IIM for STAT4 and DGKQ in the total cohort, for NAB1 and FAM167A-BLK loci in PM, and for CCR5 in inclusion body myositis. We found enrichment of variants among DNase I hypersensitivity sites and histone marks associated with active transcription within blood cells.We found novel and strong associations in IIM and PM and localized signals to single genes and immune cell types.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Arthritis & rheumatology (Hoboken, N.J.)

DOI

EISSN

2326-5205

ISSN

2326-5191

Publication Date

June 2023

Volume

75

Issue

6

Start / End Page

1021 / 1027

Related Subject Headings

  • Polymyositis
  • Myositis
  • Humans
  • Haplotypes
  • Genetic Predisposition to Disease
  • Autoimmune Diseases
  • 3204 Immunology
  • 3202 Clinical sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Rothwell, S., Amos, C. I., Miller, F. W., Rider, L. G., Lundberg, I. E., Gregersen, P. K., … Myositis Genetics Consortium. (2023). Identification of Novel Associations and Localization of Signals in Idiopathic Inflammatory Myopathies Using Genome-Wide Imputation. Arthritis & Rheumatology (Hoboken, N.J.), 75(6), 1021–1027. https://doi.org/10.1002/art.42434
Rothwell, Simon, Christopher I. Amos, Frederick W. Miller, Lisa G. Rider, Ingrid E. Lundberg, Peter K. Gregersen, Jiri Vencovsky, et al. “Identification of Novel Associations and Localization of Signals in Idiopathic Inflammatory Myopathies Using Genome-Wide Imputation.Arthritis & Rheumatology (Hoboken, N.J.) 75, no. 6 (June 2023): 1021–27. https://doi.org/10.1002/art.42434.
Rothwell S, Amos CI, Miller FW, Rider LG, Lundberg IE, Gregersen PK, et al. Identification of Novel Associations and Localization of Signals in Idiopathic Inflammatory Myopathies Using Genome-Wide Imputation. Arthritis & rheumatology (Hoboken, NJ). 2023 Jun;75(6):1021–7.
Rothwell, Simon, et al. “Identification of Novel Associations and Localization of Signals in Idiopathic Inflammatory Myopathies Using Genome-Wide Imputation.Arthritis & Rheumatology (Hoboken, N.J.), vol. 75, no. 6, June 2023, pp. 1021–27. Epmc, doi:10.1002/art.42434.
Rothwell S, Amos CI, Miller FW, Rider LG, Lundberg IE, Gregersen PK, Vencovsky J, McHugh N, Limaye V, Selva-O’Callaghan A, Hanna MG, Machado PM, Pachman LM, Reed AM, Molberg Ø, Benveniste O, Mathiesen P, Radstake T, Doria A, De Bleecker JL, De Paepe B, Maurer B, Ollier WE, Padyukov L, O’Hanlon TP, Lee A, Wedderburn LR, Chinoy H, Lamb JA, Myositis Genetics Consortium. Identification of Novel Associations and Localization of Signals in Idiopathic Inflammatory Myopathies Using Genome-Wide Imputation. Arthritis & rheumatology (Hoboken, NJ). 2023 Jun;75(6):1021–1027.
Journal cover image

Published In

Arthritis & rheumatology (Hoboken, N.J.)

DOI

EISSN

2326-5205

ISSN

2326-5191

Publication Date

June 2023

Volume

75

Issue

6

Start / End Page

1021 / 1027

Related Subject Headings

  • Polymyositis
  • Myositis
  • Humans
  • Haplotypes
  • Genetic Predisposition to Disease
  • Autoimmune Diseases
  • 3204 Immunology
  • 3202 Clinical sciences