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GWAS identifies genetic loci, lifestyle factors and circulating biomarkers that are risk factors for sarcoidosis

Author

Listed:
  • Shuai Yuan

    (Karolinska Institutet
    University of Pennsylvania Perelman School of Medicine
    Corporal Michael J. Crescenz VA Medical Center)

  • Jie Chen

    (Central South University)

  • Jiawei Geng

    (Zhejiang University School of Medicine)

  • Sizheng Steven Zhao

    (Manchester Academic Health Science Centre)

  • James Yarmolinsky

    (Imperial College London)

  • Elizabeth V. Arkema

    (Karolinska Institutet)

  • Sarah Abramowitz

    (University of Pennsylvania Perelman School of Medicine)

  • Michael G. Levin

    (Corporal Michael J. Crescenz VA Medical Center
    University of Pennsylvania Perelman School of Medicine)

  • Kostas K. Tsilidis

    (Imperial College London
    University of Ioannina School of Medicine)

  • Stephen Burgess

    (University of Cambridge
    University of Cambridge)

  • Scott M. Damrauer

    (University of Pennsylvania Perelman School of Medicine
    Corporal Michael J. Crescenz VA Medical Center)

  • Susanna C. Larsson

    (Karolinska Institutet
    Uppsala University)

Abstract

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.

Suggested Citation

  • Shuai Yuan & Jie Chen & Jiawei Geng & Sizheng Steven Zhao & James Yarmolinsky & Elizabeth V. Arkema & Sarah Abramowitz & Michael G. Levin & Kostas K. Tsilidis & Stephen Burgess & Scott M. Damrauer & S, 2025. "GWAS identifies genetic loci, lifestyle factors and circulating biomarkers that are risk factors for sarcoidosis," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57829-z
    DOI: 10.1038/s41467-025-57829-z
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    References listed on IDEAS

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    1. Claudia Giambartolomei & Damjan Vukcevic & Eric E Schadt & Lude Franke & Aroon D Hingorani & Chris Wallace & Vincent Plagnol, 2014. "Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics," PLOS Genetics, Public Library of Science, vol. 10(5), pages 1-15, May.
    2. Christiaan A de Leeuw & Joris M Mooij & Tom Heskes & Danielle Posthuma, 2015. "MAGMA: Generalized Gene-Set Analysis of GWAS Data," PLOS Computational Biology, Public Library of Science, vol. 11(4), pages 1-19, April.
    3. Mitja I. Kurki & Juha Karjalainen & Priit Palta & Timo P. Sipilä & Kati Kristiansson & Kati M. Donner & Mary P. Reeve & Hannele Laivuori & Mervi Aavikko & Mari A. Kaunisto & Anu Loukola & Elisa Lahtel, 2023. "Author Correction: FinnGen provides genetic insights from a well-phenotyped isolated population," Nature, Nature, vol. 615(7952), pages 19-19, March.
    4. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    5. Mitja I. Kurki & Juha Karjalainen & Priit Palta & Timo P. Sipilä & Kati Kristiansson & Kati M. Donner & Mary P. Reeve & Hannele Laivuori & Mervi Aavikko & Mari A. Kaunisto & Anu Loukola & Elisa Lahtel, 2023. "FinnGen provides genetic insights from a well-phenotyped isolated population," Nature, Nature, vol. 613(7944), pages 508-518, January.
    6. Alvaro N Barbeira & Milton Pividori & Jiamao Zheng & Heather E Wheeler & Dan L Nicolae & Hae Kyung Im, 2019. "Integrating predicted transcriptome from multiple tissues improves association detection," PLOS Genetics, Public Library of Science, vol. 15(1), pages 1-20, January.
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