Genetic Associates of Childhood Wheezing Phenotypes Identified

What is it about?

This study identified genetic associates of childhood wheezing disorders using a unique dataset from five UK birth cohorts. It found that genetic architecture of different wheeze phenotypes comprises a limited number of variants likely underpinning mechanisms which are shared across phenotypes, but each phenotype is also characterized by unique phenotype-specific genetic associations. The researchers identified a novel locus in chr9q21 nearby ANXA1 exclusively associated with early-onset persistent wheeze. They also found that the risk allele of rs75260654 associated with early-onset persistent wheeze is also associated with ANXA1 expression. Furthermore, they demonstrated that the pro-resolving ANXA1 may play a role in regulating the pulmonary immune response to allergen. In summary, the study used a novel approach to identify genetic associates of childhood wheezing disorders, finding unique genetic associations for each wheeze phenotype. They identified a new locus in ANXA1 and found that the risk allele of rs75260654 is associated with ANXA1 expression and early-onset persistent wheeze. The study highlights the importance of careful phenotyping in identifying precise genetic associations and subtypes of diseases.

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Why is it important?

The study is important because it sheds light on the genetic architecture of childhood wheezing disorders and identifies subsets of SNPs differentially associated with different wheezing phenotypes. This knowledge can help in understanding the underlying mechanisms and contribute to the development of targeted therapies for asthma and related conditions. Key Takeaways: 1. The study identified 44 SNPs associated with early-onset persistent wheeze, 25 SNPs associated with early-onset pre-school remitting wheeze, 33 SNPs associated with early-onset mid-childhood remitting wheeze, and 32 SNPs associated with late-onset wheeze. 2. Each wheezing phenotype comprises a limited number of variants likely underpinning shared mechanisms, but each phenotype is also characterized by unique phenotype-specific genetic associations. 3. A novel locus in chr9q21 nearby ANXA1 was exclusively associated with early-onset persistent wheeze, and the risk allele was also associated with increased ANXA1 expression. 4. The ANXA1/FPR2 axis represents an important resolution pathway in chronic inflammatory settings and may have therapeutic potential for asthma and related conditions.