| Title: | GWAS identifies genetic loci, lifestyle factors and circulating biomarkers that are risk factors for sarcoidosis |
| Journal: | Nature Communications |
| Published: | 12 Mar 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40075078/ |
| DOI: | https://doi.org/10.1038/s41467-025-57829-z |
Publication 15619
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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.</p>
17 Keywords
- Adult
- Biomarkers
- Body Mass Index
- Female
- Genetic Loci
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Life Style
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Polymorphism, Single Nucleotide
- Receptors, Interleukin
- Risk Factors
- Sarcoidosis
- Transcriptome
12 Authors
- 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
- Susanna C. Larsson
1 Application
| Application ID | Title |
|---|---|
| 72723 | Improving causal inference in rheumatic diseases research by integrating observational and genetic epidemiology |
Enabling scientific discoveries that improve human health