Effect of HLA on development of asthma

Mahdi, Batool Mutar; Al-Hadithi, Arwa Tahrir Ramadhan; Raouf, Hyam; Zalzala, Haider Hashim; Abid, Laheeb Ali; Nehad, Zena

doi:10.1016/j.amsu.2018.10.003

Cited by 11 publications

(5 citation statements)

References 14 publications

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“…To demonstrate the utility of using our resource, we explored colocalization between eGenes and complex traits that contribute to wide phenotypic variation in Cystic Fibrosis (CF) patients including pulmonary diseases (Stoltz et al, 2015), weight (Leung et al, 2017; Morison et al, 1997) as well as liver, biliary tract and gallbladder diseases (Assis and Debray, 2017; Diwakar et al, 2001; Herrmann et al, 2010) (Figure 6). We identified eight eGenes whose eQTL colocalized with GWAS signals for pulmonary diseases, of which three, HLA-B , HLA-DQA1 and HLA-DQB1 , had been previously associated with Asthma in GWAS (Kontakioti et al, 2014; Li et al, 2012; Mahdi et al, 2018) and in the UK Biobank (Vicente et al, 2017). However, the other five eGenes, including HLA-DRA (the most strongly associated), APOM , DXO , RNF5 and TAP1 were novel, that is had not been identified in GWAS.…”

Section: Resultsmentioning

confidence: 99%

Systematic genetic analysis of the MHC region reveals mechanistic underpinnings of HLA type associations with disease

D’Antonio

Reyna

Jakubosky

et al. 2019

eLife

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The MHC region is highly associated with autoimmune and infectious diseases. Here we conduct an in-depth interrogation of associations between genetic variation, gene expression and disease. We create a comprehensive map of regulatory variation in the MHC region using WGS from 419 individuals to call eight-digit HLA types and RNA-seq data from matched iPSCs. Building on this regulatory map, we explored GWAS signals for 4083 traits, detecting colocalization for 180 disease loci with eQTLs. We show that eQTL analyses taking HLA type haplotypes into account have substantially greater power compared with only using single variants. We examined the association between the 8.1 ancestral haplotype and delayed colonization in Cystic Fibrosis, postulating that downregulation of RNF5 expression is the likely causal mechanism. Our study provides insights into the genetic architecture of the MHC region and pinpoints disease associations that are due to differential expression of HLA genes and non-HLA genes.

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Section: Resultsmentioning

confidence: 99%

Systematic genetic analysis of the MHC region reveals mechanistic underpinnings of HLA type associations with disease

D’Antonio

Reyna

Jakubosky

et al. 2019

eLife

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“…To demonstrate the utility of using our resource, we explored colocalization between eGenes and complex traits that contribute to wide phenotypic variation in Cystic Fibrosis (CF) patients including pulmonary diseases (Stoltz et al, 2015), weight (Leung et al, 2017;Morison et al, 1997) as well as liver, biliary tract and gallbladder diseases (Assis and Debray, 2017;Diwakar et al, 2001;Herrmann et al, 2010) (Figure 5). We identified eight eGenes whose eQTL colocalized with GWAS signals for pulmonary diseases, of which three, HLA-B, HLA-DQA1 and HLA-DQB1, had been previously associated with Asthma in GWAS (Kontakioti et al, 2014;Li et al, 2012;Mahdi et al, 2018) and in the UK Biobank (Vicente et al, 2017). However, the other five eGenes, including HLA-DRA (the most strongly associated), APOM, DXO, RNF5 and TAP1 were novel, i.e., had not been identified in GWAS.…”

Section: Regulatory Variants In the Mhc Region Play Important Roles Imentioning

confidence: 97%

In-depth genetic analysis of 6p21.3 reveals insights into associations between HLA types and complex traits and disease

D’Antonio¹,

Reyna²,

D’Antonio‐Chronowska³

et al. 2019

Preprint

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The MHC region is highly associated with autoimmune and infectious diseases. Here we conduct an in-depth interrogation of associations between genetic variation, gene expression and disease. We create a comprehensive map of regulatory variation in the MHC region using WGS from 419 individuals to call eight-digit HLA types and RNA-seq data from matched iPSCs. Building on this regulatory map, we explored GWAS signals for 4,083 traits, detecting colocalization for 180 disease loci with eQTLs. We show that eQTL analyses taking HLA type haplotypes into account have substantially greater power compared with only using single variants. We examined the association between the 8.1 ancestral haplotype and delayed

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“…To date, the diagnosis of asthma is a complex and multistep process that requires not only a careful collection of anamnesis, but identification of all possible risk factors, including genetic predisposition, contributing to the development and severe course of asthma [ 12 , 13 ]. With the emergence of COVID-19, we have a new trigger factor that affects not only the activation of asthma but also determines the severity of the course of both COVID-19 itself and the severity of asthma [ 12 , 14 ].…”

Section: Etiology and Pathogenesis Of Asthmamentioning

confidence: 99%

Bronchial Asthma and COVID-19: Etiology, Pathological Triggers, and Therapeutic Considerations

Starshinova,

Borozinets,

Kulpina

et al. 2024

Pathophysiology

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Bronchial asthma (BA) continues to be a difficult disease to diagnose. Various factors have been described in the development of BA, but to date, there is no clear evidence for the etiology of this chronic disease. The emergence of COVID-19 has contributed to the pandemic course of asthma and immunologic features. However, there are no unambiguous data on asthma on the background and after COVID-19. There is correlation between various trigger factors that provoke the development of bronchial asthma. It is now obvious that the SARS-CoV-2 virus is one of the provoking factors. COVID-19 has affected the course of asthma. Currently, there is no clear understanding of whether asthma progresses during or after COVID-19 infection. According to the results of some studies, a significant difference was identified between the development of asthma in people after COVID-19. Mild asthma and moderate asthma do not increase the severity of COVID-19 infection. Nevertheless, oral steroid treatment and hospitalization for severe BA were associated with higher COVID-19 severity. The influence of SARS-CoV-2 infection is one of the protective factors. It causes the development of severe bronchial asthma. The accumulated experience with omalizumab in patients with severe asthma during COVID-19, who received omalizumab during the pandemic, has strongly suggested that continued treatment with omalizumab is safe and may help prevent the severe course of COVID-19. Targeted therapy for asthma with the use of omalizumab may also help to reduce severe asthma associated with COVID-19. However, further studies are needed to prove the effect of omalizumab. Data analysis should persist, based on the results of the course of asthma after COVID-19 with varying degrees of severity.

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Effect of HLA on development of asthma

Cited by 11 publications

References 14 publications

Systematic genetic analysis of the MHC region reveals mechanistic underpinnings of HLA type associations with disease

Systematic genetic analysis of the MHC region reveals mechanistic underpinnings of HLA type associations with disease

In-depth genetic analysis of 6p21.3 reveals insights into associations between HLA types and complex traits and disease

Bronchial Asthma and COVID-19: Etiology, Pathological Triggers, and Therapeutic Considerations

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