Dog ownership during infancy might attenuate the risk of persistent wheezing
In a recent study published in the Journal of Allergy and Clinical Immunology, researchers examined the gene-environment (GxE) interactions between pet ownership in infancy and the 17q12-21 (asthma-risk) locus concerning wheezing.
The heritability of asthma explained by genetic variants in recent genome-wide association studies (GWASs) has been approximately 9%, as opposed to 60%-90% estimated in extensive twin studies. GxE interactions and broad definitions of asthma likely contribute to the ‘missing’ heritability. The study team for the early life asthma research (STELAR) consortium was created using five unselected birth cohorts in the United Kingdom (UK).
Seventeen single-nucleotide polymorphisms (SNPs) in different genes in the 17q12-q21 locus have been linked to asthma, albeit no causal variant has been confirmed. Nevertheless, rs2305480, the gasdermin-B missense variant, was the lead SNP in one study on asthma exacerbations. Sensitization to pets (cats/dogs) is common in childhood asthma.
About the study
The present study evaluated the GxE interactions between the rs2305480 variant in the 17q12-q21 locus and pet (dog/cat) ownership in infancy. Data were collected from birth through adolescence through validated questionnaires in five cohorts in the STELAR consortium. The authors focused separately on cat and dog ownership in the first year of life by limiting the analysis to only dog owners, cat owners, and those who owned neither pet.
For comparison, a group of dog and cat owners was used. The researchers used five wheezing classes from latent class analysis on longitudinal wheezing data. These were – a) never/infrequent wheeze, b) early-onset preschool remitting wheeze, c) early-onset middle-childhood remitting wheeze, d) persistent wheeze, and e) late-onset wheeze.
The rs2305480 variant was genotyped in five cohorts. The broad binary definition of asthma, namely, asthma ever at age 16 (AE16), was used. The five cohorts were Ashford (ASHFORD), Avon longitudinal study of parents and children (ALSPAC), Aberdeen study of eczema and asthma to observe the effects of nutrition (SEATON), Manchester asthma and allergy study (MAAS), and Isle of Wight (IOW).
The ALSPAC cohort was separately analyzed, whereas the remaining were jointly studied (henceforth, joint cohort). A meta-analysis was performed on the summary statistics of ALSPAC and joint cohorts. The interactions between the rs2305480 genotype and pet ownership were examined using logistic regression.
Multinomial regression was performed to assess the association and interactions between rs2305480 and pet ownership. Floor dust was obtained at age 5 for the MAAS cohort, and endotoxin levels were ascertained. Endotoxin levels were tested for associations with wheezing classes and pet ownership, using multinomial regression and the Wilcoxon test, respectively.
Findings
The joint cohort had 2587 children, whereas the ALSPAC cohort had 6149 children. Notably, 90% of those classified non-asthmatic as per AE16 definition were in the ‘never/infrequent wheeze’ class. Conversely, 89% of asthmatics were in the persistent wheeze class. The meta-analysis showed that the rs2305480 variant was linked with AE16 and persistent and late-onset wheezing.
However, the meta-analysis for pet ownership showed no association between cat/dog ownership in the first year of life and asthma or wheezing type. In non-pet owners, the G allele of rs2305480 was associated with an elevated risk of AE16, persistent wheeze, and late-onset wheeze. Similarly, for cat owners, the G allele was associated with an increased risk of persistent wheezing and AE16.
No association was observed between the rs2305480 genotype and AE16 or wheezing class for dog owners. The meta-analysis of logistic models revealed that dog owners with the rs2305480 risk allele had a significantly attenuated risk of persistent wheezing. The non-pet owners carrying the (GG) risk phenotype showed a heightened prevalence of persistent wheezing.
Like non-pet owners, cat owners with the GG phenotype had a higher risk of persistent wheezing. In contrast, dog owners with the GG phenotype did not have a higher prevalence of persistent wheezing relative to other groups. Notably, higher endotoxin levels were observed in pet owners’ houses than in non-pet owners’ homes. Specifically, elevated endotoxin levels were associated with a lower risk of persistent wheezing.
Conclusions
In summary, the study showed the association between the rs2305480 risk allele and the elevated risk of asthma for the whole population. The rs2305480 allele also elevated the risk of persistent and late-onset wheezing. The authors found no association between pet ownership and asthma or wheezing outcomes in the first year of life in the whole population. However, when GxE interactions between pet ownership and genotype were tested, dog owners (only) were no longer associated with a higher risk of asthma or wheezing.
