Table 4.
Validation of the relationship between genetic variants and inhaled corticosteroid use on asthma exacerbations within Latinos (n=1,461) from GALA II and African Americans (n=563) from SAGE II*
| Study | SNP | Chr | Position | Allele† | MAF† | Gene | Parameter estimate for ICS‡ | P-value for ICS‡ | Parameter estimate for SNP‡ | P-value for SNP‡ | Parameter estimate for SNP x ICS interaction‡ | P-value for interaction‡ | P-value for joint test§ |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| GALA II | rs3827907 | 14 | 21238798 | C/T | 0.21 | EDDM3B | −0.16 | 0.521 | 0.21 | 0.194 | 0.15 | 0.503 | 0.029 |
| rs2629529 | 10 | 126534415 | C/A | 0.12 | -- | −0.12 | 0.634 | 0.17 | 0.405 | 0.08 | 0.766 | 0.281 | |
| rs73906251 | 20 | 29991274 | T/C | 0.02 | -- | −0.12 | 0.611 | −0.45 | 0.312 | 1.08 | 0.224 | 0.413 | |
| SAGE II | rs3827907 | 14 | 21238798 | C/T | 0.16 | EDDM3B | −1.01 | 0.183 | −1.04 | 0.021 | 0.96 | 0.053 | 0.041 |
| rs2629529 | 10 | 126534415 | C/A | 0.06 | -- | −0.93 | 0.204 | 0.15 | 0.794 | −0.01 | 0.995 | 0.876 | |
| rs73906251 | 20 | 29991274 | T/C | 0.08 | -- | −0.89 | 0.204 | −0.69 | 0.219 | −0.12 | 0.851 | 0.004 |
GALA II denotes the Genes-environments and Admixture in Latino Americans study; SAGE II, the Study of African Americans, Asthma, Genes, and Environments; SNP, single nucleotide polymorphism; Chr, chromosome; MAF, minor allele frequency; and ICS, inhaled corticosteroid.
The validation analyses used logistic regression to model the retrospective relationship between severe asthma exacerbation in the year prior to study enrollment (i.e., burst oral corticosteroid use, asthma-related emergency department or unscheduled physician visits, and hospitalizations for asthma) and both SNPs and SNP x ICS interactions.
The effect allele (minor allele) is shown first, and the referent allele follows. The allele frequency of the “effect” allele is provided, and in the current table, this estimate is based on the observed frequency among individuals with asthma in each study.
The parameter estimates represent the risk of having a severe asthma exacerbation in the year prior to baseline assessment (i.e., the assessment at study enrollment). A negative parameter estimate indicates that the variable was associated with a lower risk of experiencing a severe asthma exacerbation. The parameter estimate for ICS represents the effect of ICS, a dichotomous indicator variable for participant-reported ICS use at the time of study enrollment. The parameter estimate for the SNP can be interpreted as the effect on exacerbation risk for each additional “effect” allele (i.e., none [=0], one [=1], or two alleles [=2]). The parameter estimate for the interaction term can be interpreted as the combined effect of ICS use at enrollment and the number of “effect” alleles on the risk of a severe asthma exacerbation. In both GALA II and SAGE II, ICS use was represented as a single dichotomous variable based patient reported use at the time of enrollment. The parameter estimates and P-values for the ICS, SNP, and SNP x ICS interaction variables are shown for the model simultaneously including these variables, as well as adjusting for patient age, sex, BMI percentile, secondhand smoke exposure, medication step at enrollment (a proxy for asthma severity based on Expert Panel Report-3 guidelines [National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol. 120, 2007, S94-S138.]), and the first 3 principal components.
The likelihood ratio test assessed the significance of the difference in model fit between the full model (i.e., all of the aforementioned variables included) and the reduced model (i.e., the full model minus both the SNP and SNP x ICS interaction terms). In other words, a joint test was used to simultaneously assess the combined significance of the SNP and SNP x ICS interaction terms.