Patients with asthma have a higher risk of systemic lupus erythematosus: a systematic review and meta-analysis

Charoenngam, Nipith; Ponvilawan, Ben; Wongtrakul, Wasit; Ungprasert, Patompong

doi:10.1007/s10067-020-05279-x

Cited by 14 publications

(15 citation statements)

References 38 publications

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“…Another significant Harmonizome term was ‘asthma’. There is a significant association between asthma and increased risk of SLE [ 37 ]. Premature coronary heart disease is a major cause of morbidity and mortality in SLE, and is markedly increased in SLE patients compared with the general population, with epidemiologic and pathogenesis studies suggesting a great deal in common between the pathogenesis of SLE and that of atherosclerosis [ 38 ].…”

Section: Resultsmentioning

confidence: 99%

Systemic Lupus Erythematosus Patients with DNASE1L3·Deficiency Have a Distinctive and Specific Genic Circular DNA Profile in Plasma

Gerovska

Araúzo-Bravo

2023

Cells

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Cell-free (cf) extrachromosomal circular DNA (eccDNA) has a potential clinical application as a biomarker. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a complex immunological pathogenesis, associated with autoantibody synthesis. A previous study found that SLE patients with deoxyribonuclease 1-like 3 (DNASE1L3) deficiency exhibit changes in the frequency of short and long eccDNA in plasma compared to controls. Here, using the DifCir method for differential analysis of short-read sequenced purified eccDNA data based on the split-read signal of the eccDNA on circulomics data, we show that SLE patients with DNASE1L3 deficiency have a distinctive profile of eccDNA excised by gene regions compared to controls. Moreover, this profile is specific; cf-eccDNA from the top 93 genes is detected in all SLE with DNASE1L3 deficiency samples, and none in the control plasma. The top protein coding gene producing eccDNA-carrying gene fragments is the transcription factor BARX2, which is involved in skeletal muscle morphogenesis and connective tissue development. The top gene ontology terms are ‘positive regulation of torc1 signaling’ and ‘chondrocyte development’. The top Harmonizome terms are ‘lymphopenia’, ‘metabolic syndrome x’, ‘asthma’, ‘cardiovascular system disease‘, ‘leukemia’, and ‘immune system disease’. Here, we show that gene associations of cf-eccDNA can serve as a biomarker in the autoimmune rheumatic diseases.

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Section: Resultsmentioning

confidence: 99%

Systemic Lupus Erythematosus Patients with DNASE1L3·Deficiency Have a Distinctive and Specific Genic Circular DNA Profile in Plasma

Gerovska

Araúzo-Bravo

2023

Cells

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“…We identi ed that the genes regulated by asthmaassociated spatial eQTLs in the lung are also regulated by spatial eQTLs associated with various asthma endotypes, allergic and autoimmune disorders, metabolite levels, and traits related to the use of asthma medication. For example, variants associated with SLE risk, a known comorbidity of asthma (pooled odds ratio (OR): 1.37; 95% CI 1.14-1.65; I2 = 67%) (46), regulate pleiotropic genes that are regulated by asthma-associated spatial eQTLs. The identi cation of 22 genes causally related to asthma through Mendelian Randomization as being pleiotropic and linked to other traits in our analysis further supports the existence of shared molecular pathways that could contribute to comorbidity risk (41).…”

Section: Discussionmentioning

confidence: 99%

De novo identification of complex traits associated with asthma

Zaied

Fadason

O’Sullivan

2023

Preprint

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Network analysis is a powerful approach for untangling the relationships between complex diseases. Here, we integrated information on physical contacts between common single nucleotide polymorphisms (SNPs) and gene expression with expression quantitative trait loci (eQTL) data from the lung and whole blood to construct two tissue-specific spatial gene regulatory networks (GRN). From these GRNs, we located the genes that are functionally affected by asthma-associated eQTLs to identify the asthma GRN. We then expanded outwards to identify curated protein-protein interactions occurring 1 to 4 edges away from the asthma GRN. The eQTLs spatially regulating the identified genes were used to interrogate the GWAS Catalog to identify enriched traits (hypergeometric test; FDR≤0.05) within the asthma GRN and each of the 4 levels. This led to the de novo identification of traits both previously reported (e.g., depressive symptoms and lung cancer) and unreported (e.g., reticulocyte count) to be comorbid or associated with asthma. It additionally pinpoints the variants and genes that link asthma to the identified asthma-associated traits, a subset of which was replicated in a comorbidity analysis using health records of 26,781 asthma patients in New Zealand. Our discovery approach identifies enriched traits in the regulatory space proximal to asthma, in the tissue of interest, without a priori selection of the interacting traits. The predictions it makes expand our understanding of possible shared molecular interactions and therapeutic targets for asthma, where no cure is currently available.

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“…), SLE, and sarcoidosis, all of which are conditions known to be multimorbid with asthma. For instance, metanalysis studies report an increased risk for the development of SLE in asthmatics (pooled odds ratio (OR): 1.37; 95% CI 1.14-1.65; I2 = 67%) (23). Additionally, the genetic risk of sarcoidosis, which is a granulomatous multisystem disease of unknown etiology and pathology that predominantly affects the lungs (47,48), had signi cant pleiotropy with the genetic risk of asthma (R 2 =2.03%; p=8.89×10 −9 ) (26).…”

Section: Discussionmentioning

confidence: 99%

“…This agnostic approach enabled us to de novo identify diseases that are associated with asthma such as systemic lupus erythematosus (SLE), sarcoidosis, and lung cancer. These disease have been previously observed to be multimorbid with asthma (23)(24)(25)(26). We also identi ed traits that are proximal to the asthma disease module whose association with asthma are yet to be con rmed (e.g., disc degeneration and hip circumference).…”

Section: Introductionmentioning

confidence: 92%

De novo identification of complex multimorbid conditions by integration of gene regulation and protein interaction networks with genome-wide association studies

Zaied

Fadason

O’Sullivan

2022

Preprint

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Network analysis represents a powerful approach for untangling the relationships between complex diseases. Here, we integrated information on physical contacts between common single nucleotide polymorphisms (SNPs; MAF≥0.05) and expressed genes (TPM>0.1), with expression quantitative trait loci (eQTL) data from whole blood to construct a blood-specific spatial gene regulatory network (GRN). Using this GRN, we located the genes that are functionally affected by asthma-associated SNPs to identify the asthma-specific module. We then expanded outwards to identify curated protein-protein interactions occurring 1 to 4 edges away from the asthma module. The eQTLs spatially regulating the identified genes were used to interrogate the GWAS Catalog to identify enriched traits (hypergeometric test; FDR≤0.05) within each of the 4 levels. This led to de novo identification of traits both previously reported (e.g., sarcoidosis and lung cancer) and unreported (e.g., disc-degeneration) to be multimorbid with asthma, and pinpoints the variants and genes bridging asthma to the multimorbidities. Our discovery approach identifies significantly enriched traits in the regulatory space proximal to a disease of interest, in the tissue of interest, without a priori selection of the interacting diseases. The predictions it makes expand our understanding of possible shared therapeutic targets, especially for diseases such as asthma where no cure is currently available.

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Patients with asthma have a higher risk of systemic lupus erythematosus: a systematic review and meta-analysis

Cited by 14 publications

References 38 publications

Systemic Lupus Erythematosus Patients with DNASE1L3·Deficiency Have a Distinctive and Specific Genic Circular DNA Profile in Plasma

Systemic Lupus Erythematosus Patients with DNASE1L3·Deficiency Have a Distinctive and Specific Genic Circular DNA Profile in Plasma

De novo identification of complex traits associated with asthma

De novo identification of complex multimorbid conditions by integration of gene regulation and protein interaction networks with genome-wide association studies

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