Publications

Functional link between sarcoidosis-associated gene variants and quantitative levels of bronchoalveolar lavage fluid cell types

https://pubmed.ncbi.nlm.nih.gov/36824606/

Abo Al Hayja M, Kullberg S, Eklund A, Padyukov L, Grunewald J, Rivera NV. Functional link between sarcoidosis-associated gene variants and quantitative levels of bronchoalveolar lavage fluid cell types. Front Med (Lausanne). 2023 Feb 7;10:1061654. doi: 10.3389/fmed.2023.1061654. PMID: 36824606; PMCID: PMC9941743.

Genetic variants associated with sarcoidosis are likely to modulate quantitative levels of BAL cell types and may regulate gene expression in immune cell populations. Thus, the role of sarcoidosis-associated gene-variants may be to influence cellular phenotypes underlying the disease immunopathology.

Gene-based analysis in LS and non-LS sex groups across all cohorts at p < 2e-6. ls, LS in SWE; non-ls1, non-LS in SWE and GER; non-ls2, non-LS in SWE, GER, and USA-AA; shared, genes shared by sex groups; male, genes associated with males only; female, genes associated with females only.

Sex differences in the genetics of sarcoidosis across European and African ancestry populations

https://pubmed.ncbi.nlm.nih.gov/37250650/

Xiong Y, Kullberg S, Garman L, Pezant N, Ellinghaus D, Vasila V, Eklund A, Rybicki BA, Iannuzzi MC, Schreiber S, Müller-Quernheim J, Montgomery CG, Grunewald J, Padyukov L, Rivera NV. Sex differences in the genetics of sarcoidosis across European and African ancestry populations. Front Med (Lausanne). 2023 May 11;10:1132799. doi: 10.3389/fmed.2023.1132799. Erratum in: Front Med (Lausanne). 2024 Feb 21;11:1382584. PMID: 37250650; PMCID: PMC10213734.

Sex differences in the susceptibility of sarcoidosis are unknown. The study aimed to identify sex-dependent genetic variations in two clinical sarcoidosis phenotypes: Löfgren's syndrome (LS) and non-Löfgren's syndrome (non-LS). The findings of this study provided new evidence for a sex bias underlying sarcoidosis genetic architecture, particularly in clinical phenotypes LS and non-LS. Biological sex likely plays a role in disease mechanisms in sarcoidosis.

Genomic regions interacting with smoking in LS. From the center, the first circos depicts the odds ratio due to double exposure i.e., the effect of both SNP allele and smoking (in red). The second circos illustrates the effect of smoking (green). The third circos depicts the effect of the SNP allele (blue). The fourth circos shows the autosomal chromosomes (1–22) ideogram and highlights the genomic loci interacting with smoking.

A Gene-Environment Interaction Between Smoking and Gene polymorphisms Provides a High Risk of Two Subgroups of Sarcoidosis

https://pubmed.ncbi.nlm.nih.gov/31819081/

Rivera NV, Patasova K, Kullberg S, Diaz-Gallo LM, Iseda T, Bengtsson C, Alfredsson L, Eklund A, Kockum I, Grunewald J, Padyukov L. A Gene-Environment Interaction Between Smoking and Gene polymorphisms Provides a High Risk of Two Subgroups of Sarcoidosis. Sci Rep. 2019 Dec 9;9(1):18633. doi: 10.1038/s41598-019-54612-1. PMID: 31819081; PMCID: PMC6901455.

The findings in this study suggest that sarcoidosis risk is modulated by smoking due to genetic susceptibility. Therefore, patients having certain gene variants, are at a higher risk for the disease. Consideration of individual's genetic predisposition is crucial to quantify effects of smoking in sarcoidosis.

Photo: Mesargen

Common variants of T-cells contribute differently to phenotypic variation in sarcoidosis

https://pubmed.ncbi.nlm.nih.gov/28717140/

Rivera NV, Hagemann-Jensen M, Ferreira MAR, Kullberg S, Eklund A, Martin NG, Padyukov L, Grunewald J. Common variants of T-cells contribute differently to phenotypic variation in sarcoidosis. Sci Rep. 2017 Jul 17;7(1):5623. doi: 10.1038/s41598-017-05754-7. PMID: 28717140; PMCID: PMC5514043.

Differences in significant polygenic scores, presenceof pleiotropy, and distinct genetic factors provide further insights on how genetic variants and genesassociated with relative levels of T-cell subtypes contribute differently to sarcoidosis phenotypes.

Lofgren syndrome (LS), non-Lofgren syndrome (non-LS), and healthy controls (HC)

Regional association plots of chr6:25527073–33191175. Löfgren’s syndrome (LS)-associated single-nucleotide polymorphisms (SNPs) (top) at PGC < 5 × 10−8 highlight region chr6:28910128–3295881. Non-LS–associated SNPs (bottom) at PGC < 5 × 10−8 highlight region chr6: 32447326–32789970. PGC = genomic-controlled P value.

High-Density Genetic Mapping Identifies New Susceptibility Variants in Sarcoidosis Phenotypes and Shows Genomic-driven Phenotypic Differences

https://pubmed.ncbi.nlm.nih.gov/26651848/

Rivera NV, Ronninger M, Shchetynsky K, Franke A, Nöthen MM, Müller-Quernheim J, Schreiber S, Adrianto I, Karakaya B, van Moorsel CH, Navratilova Z, Kolek V, Rybicki BA, Iannuzzi MC, Petrek M, Grutters JC, Montgomery C, Fischer A, Eklund A, Padyukov L, Grunewald J. Am J Respir Crit Care Med. 2016 May 1;193(9):1008-22. doi: 10.1164/rccm.201507-1372OC. PMID:26651848

Genetic investigations of sarcoidosis sub-phenotypes: Lofgren syndrome (LS) and Non-Lofgren syndrome (non-LS) – revealed that these sub-phenotypes have their own genetic architecture with a common genomic overlap located on the extended major histocompatibility complex (MHC) region.