UK researchers linked genetic variations at the 17q21 locus on chromosome 17 to childhood asthma and certain wheezing phenotypes, but not to more general phenotypes such as atopy or lung function, according to results of an international study.
Investigators reviewed data on 7045 children, identifying 244 independent single nucleotide polymorphisms (SNPs) and 13 previously identified asthma SNPs between 34 Mb and 36 Mb on chromosome 17. The associations were examined between the SNPs and early wheezing phenotypes, doctor-diagnosed asthma and atopy at 7.5 years, and bronchial hyperresponsiveness (BHR) and lung function at 8.5 years.
Among all children, 19.7% had asthma, 46.7% had an asthmatic or allergic mother, 22.3% were exposed to maternal smoking during pregnancy, and 20.1% were atopic. Nearly 70% had never/infrequent wheezing, 10.2% had transient early wheezing, 7.5% had prolonged early wheezing, 2.3% had intermediate onset, 4.8% late onset, and 7.0% had persistent wheezing.
The strongest associations with doctor-diagnosed asthma were seen with the asthma-related SNPs rs9303277 near IKZF3 and rs2290400 near GSDML, both at odds ratios (ORs) of 1.30. For BHR, the strongest associations were with rs1042658 near CSF3 and with rs3859192 near GSDM1, at ORs of 1.20 and 1.19, respectively.
“Elucidation of causal mechanisms has the potential to facilitate disease prediction in children with wheezing in the preschool years, to contribute to the separation of discrete phenotypes of childhood asthma, and to identify risk factors that might be targets for primary or secondary disease prevention,” the authors wrote.