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GWAS identifies genetic loci, lifestyle factors and circulating biomarkers that are risk factors for sarcoidosis
Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden.;Univ Penn, Perelman Sch Med, Dept Surg, Philadelphia, PA 19104 USA.;Corporal Michael J Crescenz VA Med Ctr, Philadelphia, PA 19104 USA..
Cent South Univ, Xiangya Hosp 3, Dept Gastroenterol, Changsha, Peoples R China..
Zhejiang Univ, Affiliated Hosp 2, Ctr Clin Big Data & Analyt, Dept Big Data Hlth Sci,Sch Publ Hlth,Sch Med, Hangzhou, Peoples R China..
Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Biol Med & Hlth, Sch Biol Sci,Div Musculoskeletal & Dermatol Sci,Ct, Manchester, England..
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2025 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 16, no 1, article id 2481Article in journal (Refereed) Published
Abstract [en]

Sarcoidosis is a complex inflammatory disease with a strong genetic component. Here, we perform a genome-wide association study in 9755 sarcoidosis cases to identify risk loci and map associated genes. We then use transcriptome-wide association studies and enrichment analyses to explore pathways involved in sarcoidosis and use Mendelian randomization to examine associations with modifiable factors and circulating biomarkers. We identify 28 genomic loci associated with sarcoidosis, with the C1orf141-IL23R locus showing the largest effect size. We observe gene expression patterns related to sarcoidosis in the spleen, whole blood, and lung, and highlight 75 tissue-specific genes through transcriptome-wide association studies. Furthermore, we use enrichment analysis to establish key roles for T cell activation, leukocyte adhesion, and cytokine production in sarcoidosis. Additionally, we find associations between sarcoidosis and genetically predicted body mass index, interleukin-23 receptor, and eight circulating proteins.

Place, publisher, year, edition, pages
Springer Nature, 2025. Vol. 16, no 1, article id 2481
National Category
Medical Genetics and Genomics Respiratory Medicine and Allergy Cell and Molecular Biology Immunology in the Medical Area
Identifiers
URN: urn:nbn:se:uu:diva-553533DOI: 10.1038/s41467-025-57829-zISI: 001443899000015PubMedID: 40075078OAI: oai:DiVA.org:uu-553533DiVA, id: diva2:1948342
Funder
Swedish Research Council, 2022-00826Swedish Heart Lung Foundation, 20200452Swedish Cancer Society, 20 1299Swedish Cancer SocietySwedish Research Council, 2019-00977Forte, Swedish Research Council for Health, Working Life and Welfare, 2018-00123Swedish Heart Lung Foundation, 20190247Available from: 2025-03-28 Created: 2025-03-28 Last updated: 2025-03-28Bibliographically approved

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