Assessing causal relationships between gut microbiota and asthma: evidence from two sample Mendelian randomization analysis DOI Creative Commons
Rong Li,

Qi Guo,

Jian Zhao

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 19, 2023

Background Accumulating evidence has suggested that gut microbiota dysbiosis is commonly observed in asthmatics. However, it remains unclear whether a cause or consequence of asthma. We aimed to examine the genetic causal relationships with asthma and its three phenotypes, including adult-onset asthma, childhood-onset moderate-severe Methods To elucidate causality we applied two sample Mendelian randomization (MR) based on largest publicly available genome-wide association study (GWAS) summary statistics. Inverse variance weighting meta-analysis (IVW) was used obtain main estimates; Weighted median, MR-Egger, Robust Adjusted Profile Score (MR-RAPS), Maximum likelihood method (ML), MR pleiotropy residual sum outlier (MR-PRESSO) methods were sensitivity analyses. Finally, reverse analysis performed evaluate possibility causation. Results In absence heterogeneity horizontal pleiotropy, IVW revealed genetically predicted Barnesiella RuminococcaceaeUCG014 positively correlated risk while between CandidatusSoleaferrea negative. And for phenotypes Akkermansia reduced Collinsella increased FamilyXIIIAD3011group , Eisenbergiella Ruminiclostridium6 (all P <0.05). The didn’t find supporting from genus. Conclusion This microbial genera causally associated as well phenotypes. findings deepened our understanding role pathology which emphasizes potential opening up new vista prevention diagnosis

Language: Английский

Cell-type-specific and disease-associated expression quantitative trait loci in the human lung DOI Creative Commons
Heini M. Natri, Christina B. Azodi,

Lance Peter

et al.

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(4), P. 595 - 604

Published: March 28, 2024

Abstract Common genetic variants confer substantial risk for chronic lung diseases, including pulmonary fibrosis. Defining the control of gene expression in a cell-type-specific and context-dependent manner is critical understanding mechanisms through which variation influences complex traits disease pathobiology. To this end, we performed single-cell RNA sequencing tissue from 66 individuals with fibrosis 48 unaffected donors. Using pseudobulk approach, mapped quantitative trait loci (eQTLs) across 38 cell types, observing both shared regulatory effects. Furthermore, identified interaction eQTLs demonstrated that class associations more likely to be linked cellular dysregulation Finally, connected their targets disease-relevant types. These results indicate context determines impact on implicates context-specific as key regulators homeostasis disease.

Language: Английский

Citations

23
Shared genetic investigation of asthma and blood eosinophils in relation to chronic rhinosinusitis DOI Creative Commons

Xian Li,

Jingyun Li, Shibei Xue

et al.

Allergy Asthma and Clinical Immunology, Journal Year: 2025, Volume and Issue: 21(1)

Published: March 17, 2025

Abstract Background An epidemiological association among asthma, blood eosinophil level and chronic rhinosinusitis (CRS) is well established, but whether consistent genetic relationships exist, this reflects a shared etiology between CRS asthma or remains unclear. Methods Data from patients ( N = 1,255) healthy controls 1,032) were reviewed retrospectively to investigate associations clinical characteristics CRS. white cells in the UK biobank 173,480), Trans-National Asthma Genetic Consortium (127,669) 272,922) nasal polyps 264,107) FinnGen consortium used conduct study, including linkage disequilibrium score regression analysis detect aforementioned variables, Mendelian randomization (MR) causal of levels on CRS, Bayesian co-localization consolidate MR findings identify signals. Results We found that count, percentages positive correlations with (all q < 0.0001) (CRSwNP) both our observational study. Through colocalization analysis, 4 loci are CRSwNP, 7 2 unique count 3 CRSwNP. Conclusions These contribute understanding etiology, provide insights for intervention treatment target comorbid high levels.

Language: Английский

Citations

2
Shared genetics of asthma and mental health disorders: a large-scale genome-wide cross-trait analysis DOI Open Access
Zhaozhong Zhu, Xi Zhu,

Cong-Lin Liu

et al.

European Respiratory Journal, Journal Year: 2019, Volume and Issue: 54(6), P. 1901507 - 1901507

Published: Oct. 16, 2019

Epidemiological studies demonstrate an association between asthma and mental health disorders, although little is known about the shared genetics causality of this association. Thus, we aimed to investigate causal link disorders. We conducted a large-scale genome-wide cross-trait study genetic overlap from UK Biobank eight disorders Psychiatric Genomics Consortium: attention deficit hyperactivity disorder (ADHD), anxiety (ANX), autism spectrum disorder, bipolar eating major depressive (MDD), post-traumatic stress schizophrenia (sample size 9537–394 283). In single-trait analysis, replicated 130 previously reported loci discovered 31 novel independent that are associated with asthma. identified ADHD, ANX MDD have strong correlation at level. Cross-trait meta-analysis seven jointly one locus ANX, 10 MDD. Functional analysis revealed variants regulated gene expression in tissues belonging exocrine/endocrine, digestive, respiratory haemic/immune systems. Mendelian randomisation analyses suggested ADHD (including 6.7% sample asthma) might increase risk This potential links three (ADHD, MDD). Such implicate new biological functions common among them.

Language: Английский

Citations

144
The genetics of asthma and the promise of genomics-guided drug target discovery DOI

Z. Elhusseini,

Reinoud Gosens, Frank J. Dekker

et al.

The Lancet Respiratory Medicine, Journal Year: 2020, Volume and Issue: 8(10), P. 1045 - 1056

Published: Sept. 7, 2020

Language: Английский

Citations

131
Adult‐onset eosinophilic airway diseases DOI Open Access
Koichiro Asano, Shigeharu Ueki, Mayumi Tamari

et al.

Allergy, Journal Year: 2020, Volume and Issue: 75(12), P. 3087 - 3099

Published: Oct. 11, 2020

Abstract Eosinophilic airway inflammation is one of the cardinal features allergic diseases such as atopic asthma and rhinitis. These childhood‐onset conditions are mediated by allergen allergen‐specific IgE often accompanied other including food allergy eczema. They can develop consecutively in same patient, which referred to an march. In contrast, some phenotypes asthma, nonsteroidal anti‐inflammatory drugs‐exacerbated disease (N‐ERD), chronic rhinosinusitis with nasal polyps (CRSwNP)/eosinophilic CRS bronchopulmonary aspergillosis/mycosis (ABPA/ABPM) adult‐onset diseases, characterized prominent peripheral blood eosinophilia. Most these conditions, except for ABPA/ABPM, nonatopic, coexistence multiple eosinophilic systemic disease, granulomatosis polyangiitis (EGPA), common. this review, we focus on eosinophil biology, genetics clinical characteristics pathophysiology N‐ERD, CRSwNP/eosinophilic CRS, ABPA/ABPM EGPA, while exploring common genetic, immunological pathological among diseases.

Language: Английский

Citations

83
Advances in asthma and allergic disease genetics: Is bigger always better? DOI Creative Commons
Nathan Schoettler, Elke Rodríguez, Stephan Weidinger

et al.

Journal of Allergy and Clinical Immunology, Journal Year: 2019, Volume and Issue: 144(6), P. 1495 - 1506

Published: Nov. 1, 2019

This review focuses on genome-wide association studies (GWASs) of asthma and allergic diseases published between January 1, 2018, June 30, 2019. During this time period, there were 38 GWASs reported in 19 articles, including the largest performed to date for many these conditions. Overall, we learned that childhood-onset is associated with most independent loci compared other defined groups disease cases; adult-onset moderate-to-severe are fewer genes, which largely a subset those asthma. There significant genetic overlap diseases, particularly respect asthma, involves genes reflect importance barrier function biology, HLA region frequently overall both diseases. Although African American Latino/Hispanic populations during they still significantly underpowered European ancestry, highlighting need larger studies, patients important carry greatest burden disease.

Language: Английский

Citations

82
Genetic analyses identify GSDMB associated with asthma severity, exacerbations, and antiviral pathways DOI
Xingnan Li, Stephanie A. Christenson, Brian D. Modena

et al.

Journal of Allergy and Clinical Immunology, Journal Year: 2020, Volume and Issue: 147(3), P. 894 - 909

Published: Aug. 11, 2020

Language: Английский

Citations

73
Multi-ancestry meta-analysis of asthma identifies novel associations and highlights the value of increased power and diversity DOI Creative Commons
Kristin Tsuo, Wei Zhou, Ying Wang

et al.

Cell Genomics, Journal Year: 2022, Volume and Issue: 2(12), P. 100212 - 100212

Published: Nov. 8, 2022

Asthma is a complex disease that varies widely in prevalence across populations. The extent to which genetic variation contributes these disparities unclear, as the genetics underlying asthma have been investigated primarily populations of European descent. As part Global Biobank Meta-analysis Initiative, we conducted large-scale genome-wide association study (153,763 cases and 1,647,022 controls) via meta-analysis 22 biobanks spanning multiple ancestries. We discovered 179 asthma-associated loci, 49 were not previously reported. Despite wide range among biobanks, found largely consistent effects also improved polygenic risk prediction non-European compared with previous studies. Additionally, considerable overlap between age-of-onset subtypes comorbid diseases. Our work underscores multi-factorial nature development offers insight into its shared architecture.

Language: Английский

Citations

68
The impact of cell type and context-dependent regulatory variants on human immune traits DOI Creative Commons
Zepeng Mu, Wei Wei, Benjamin Fair

et al.

Genome biology, Journal Year: 2021, Volume and Issue: 22(1)

Published: April 29, 2021

Abstract Background The vast majority of trait-associated variants identified using genome-wide association studies (GWAS) are noncoding, and therefore assumed to impact gene regulation. However, the loci unexplained by regulatory quantitative trait (QTLs). Results We perform a comprehensive characterization putative mechanisms which GWAS human immune traits. By harmonizing four major QTL studies, we identify 26,271 expression QTLs (eQTLs) 23,121 splicing (sQTLs) spanning 18 cell types. Our colocalization analyses between from 72 reveals that genetic effects on RNA in cells colocalize with 40.4% for immune-related traits, many cases increasing fraction colocalized two fold compared previous studies. Notably, find largest contributors this increase QTLs, average 14% all do not eQTLs. contrast, type-specific eQTLs, eQTLs small effect sizes contribute very few new colocalizations. To investigate 60% remain unexplained, collect H3K27ac CUT&Tag data rheumatoid arthritis healthy controls, large-scale differences different disease contexts, including at regions overlapping loci. Conclusion Altogether, our work supports as an important mediator suggests must expand study processes contexts improve functional interpretation yet

Language: Английский

Citations

59
Eight novel susceptibility loci and putative causal variants in atopic dermatitis DOI
Nao Tanaka, Masaru Koido, Akari Suzuki

et al.

Journal of Allergy and Clinical Immunology, Journal Year: 2021, Volume and Issue: 148(5), P. 1293 - 1306

Published: June 8, 2021

Language: Английский

Citations

58