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Asthma is a prevalent chronic respiratory condition marked by inflammation and hyperresponsiveness of the airways. Its pathophysiology involves complex interactions among inflammatory pathways, immune responses, and neural mechanisms.
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Asthma is a chronic pulmonary condition involving inflammation of the airways, hyper-reactivity, and reversible obstruction of the airways. This condition can significantly impact a person's quality of life, making breathing difficult and leading to distressing symptoms.
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In addition to multiple alleles at the same locus influencing traits, numerous genes or alleles at different locations may interact and influence phenotypes in a phenomenon called epistasis. For example, rabbit fur can be black or brown depending on whether the animal is homozygous dominant or heterozygous at a TYRP1 locus. However, if the rabbit is also homozygous recessive at a locus on the tyrosinase gene (TYR), it will have an unshaded coat that appears white, regardless of its TYRP1...
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Causality Between 91 Circulating Inflammatory Proteins and Various Asthma Phenotypes: A Mendelian Randomization

Shiyao Zhang1, Xiuying Zhang2, Chenghao Wei1

  • 1Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People's Republic of China.

Immunotargets and Therapy
|November 11, 2024
PubMed
Summary

This study used Mendelian randomization to explore links between inflammatory proteins and asthma. Increased CST5 protein is linked to higher non-allergic asthma risk, while LIF-R is associated with lower childhood asthma risk.

Keywords:
allergic asthmaasthmachildhood asthmainflammatory proteinmendelian randomizationnon-allergic asthmaobesity related asthmasuggestive for eosinophilic asthma

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Area of Science:

  • Genetics
  • Immunology
  • Epidemiology

Background:

  • Asthma is a complex respiratory condition with various phenotypes.
  • Circulating inflammatory proteins are implicated in asthma pathogenesis.
  • Understanding causal relationships can inform targeted therapies.

Purpose of the Study:

  • To investigate potential causal links between 91 circulating inflammatory proteins and diverse asthma phenotypes.
  • To leverage Mendelian randomization (MR) for robust causal inference.
  • To identify specific inflammatory proteins associated with increased or decreased asthma risk.

Main Methods:

  • Utilized genome-wide association studies (GWAS) data for 91 inflammatory proteins from 14,824 participants.
  • Derived asthma phenotypes from the FinnGen Biobank.
  • Employed inverse variance weighting (IVW) as the primary MR analysis method, with sensitivity analyses including MR-Egger and weighted median.
  • Assessed pleiotropy and heterogeneity using MR-Egger intercept and Cochran's Q tests.

Main Results:

  • Identified 30 potential causal relationships between inflammatory proteins and asthma phenotypes.
  • After FDR correction, CST5 protein levels showed a significant association with increased risk of non-allergic asthma (OR=1.184).
  • LIF-R protein levels were significantly associated with a reduced risk of childhood asthma (OR=0.723).

Conclusions:

  • Elevated CST5 levels are causally associated with an increased risk of non-allergic asthma.
  • Reduced LIF-R levels are causally associated with a decreased risk of asthma in children.
  • These findings highlight specific inflammatory proteins as potential therapeutic targets for distinct asthma subtypes.