Genetic Architecture of Idiopathic Inflammatory Myopathies From Meta-Analyses.
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023728%3A_____%2F25%3AN0000086" target="_blank" >RIV/00023728:_____/25:N0000086 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1002/art.43088" target="_blank" >https://doi.org/10.1002/art.43088</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/art.43088" target="_blank" >10.1002/art.43088</a>
Alternative languages
Result language
angličtina
Original language name
Genetic Architecture of Idiopathic Inflammatory Myopathies From Meta-Analyses.
Original language description
Idiopathic inflammatory myopathies (IIMs, myositis) are rare systemic autoimmune disorders that lead to muscle inflammation, weakness, and extramuscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome-wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome-wide myositis studies and analyzed the largest myositis data set to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes. We performed association analyses on 14,903 individuals (3,206 patients and 11,697 controls) with genotypes and imputed data from the Trans-Omics for Precision Medicine reference panel. Fine-mapping and expression quantitative trait locus colocalization analyses in myositis-relevant tissues indicated potential causal variants. Functional annotation and network analyses using the random walk with restart (RWR) algorithm explored underlying genetic networks and drug repurposing opportunities. Our analyses identified novel risk loci and susceptibility genes, such as FCRLA, NFKB1, IRF4, DCAKD, and ATXN2 in overall IIMs; NEMP2 in polymyositis; ACBC11 in dermatomyositis; and PSD3 in myositis with anti-histidyl-transfer RNA synthetase autoantibodies (anti-Jo-1). We also characterized effects of HLA region variants and the role of C4. Colocalization analyses suggested putative causal variants in DCAKD in skin and muscle, HCP5 in lung, and IRF4 in Epstein-Barr virus (EBV)-transformed lymphocytes, lung, and whole blood. RWR further prioritized additional candidate genes, including APP, CD74, CIITA, NR1H4, and TXNIP, for future investigation. Our study uncovers novel genetic regions contributing to IIMs, advancing our understanding of myositis pathogenesis and offering new insights for future research.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30226 - Rheumatology
Result continuities
Project
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Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ARTHRITIS & RHEUMATOLOGY
ISSN
2326-5191
e-ISSN
2326-5205
Volume of the periodical
77
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
5
Pages from-to
750-764
UT code for WoS article
001420150200001
EID of the result in the Scopus database
2-s2.0-85219194691