asthma cases , unaffected controls , asthmacase parent trios , and extended families were recruited in clinics in the u.s , mexico , and barbados . detailed descriptions of the individual studies , ascertainment schemes , genotyping platforms , quality control ( qc ) protocols , and statistical analyses for the primary association testing are described in the supplementary note online . the common set of snps consisted of all phase 2 , release 21 consensus hapmap variants . prior to genotype imputation , each center oriented their snps to the plus strand , and filtered for call rates ( > 95% ) and consistency with hardy - weinberg expectations ( p > 10 for case / control studies , p > 10 for trio studies ) . genotype imputation using hapmap reference panels were performed separately in each sample with the program mach , and associations were tested using the genotype dosages that are part of the imputation algorithms output , with adjustments for admixture in the african american and latino case - control samples ( see supplementary note online ) . the shared summary files contained the snp identifiers ( rs number , chromosome , position , alleles ) , snp qc metrics ( call rate , hardy - weinberg equilibrium p - value , imputation quality metrics ) , and information related to the test for association ( allele frequencies in cases and controls or in the transmitted and untransmitted alleles in trios , association p - value , odds ratios with standard errors ) . reference alleles were assigned as the allele coded 0 in the hapmap release 21 phased consensus haplotypes during genotype imputation in mach . the qc checks performed on summary file data included consistency in reference allele and strand orientation ( see supplementary figs . 1315 online ) , and imputation quality ( see supplementary fig . 16 online ) . snps with imputation quality scores below a threshold were removed from the analysis ( rsq < 0.3 or < 0.5 for the barbados study ) . qq plots were visually inspected to compare the distribution of association p - values for genotyped and imputed markers separately for each cohort . the meta - analysis searched for asthma susceptibility variants for which the same allele was associated with asthma in the different studies . for each study , we constructed a test statistic that has a standard normal distribution under the null hypothesis of no association and captures the direction of the effect ( i.e. , the statistic was positive if the reference allele was associated with an increased risk of asthma ) . the meta - analysis test statistic was calculated as a linear combination of the individual study scores with weights proportional to the square root of the number of cases ( or trios ) . odds ratios were calculated by combining linearly log odds ratios with weights reflecting the standard errors from the genome - wide association studies . detailed descriptions of these samples , genotyping technologies , qc protocols , and statistical analyses are described in the supplementary note online . the combined analysis of the replication samples was performed in a similar manner to the meta - analysis . for each study , we constructed a test statistic that had standard normal distribution under the null hypothesis of no association , and that also captured the direction of the effect . a combined test statistic was calculated as a linear combination of the individual study scores with weights proportional to the square root of the number of cases , and p - values were obtained using normal approximations . pilot data from the 1000 genomes project ( august 2010 haplotypes ) was used to impute a 2 mb region surrounding the pyhin1 gene in all studies using impute2 . the eur haplotypes ( european ) were used as a reference for the european american studies ( assuming an effective population size [ ne ] of 11418 ) , the eur and afr ( african ) haplotypes were used as a reference for the african american studies ( assuming ne=15000 ) , and the eur , afr , and asn ( asian haplotypes ) were used as a reference for the latino studies ( assuming ne=15000 ) . individual genotypes were filtered for probabilities > 90% , and only snps with call rates > 90% were included in allelic tests of association . for family - based studies , snps with mendelian errors were removed . asthma cases , unaffected controls , asthmacase parent trios , and extended families were recruited in clinics in the u.s , mexico , and barbados . detailed descriptions of the individual studies , ascertainment schemes , genotyping platforms , quality control ( qc ) protocols , and statistical analyses for the primary association testing are described in the supplementary note online . the common set of snps consisted of all phase 2 , release 21 consensus hapmap variants . prior to genotype imputation , each center oriented their snps to the plus strand , and filtered for call rates ( > 95% ) and consistency with hardy - weinberg expectations ( p > 10 for case / control studies , p > 10 for trio studies ) . genotype imputation using hapmap reference panels were performed separately in each sample with the program mach , and associations were tested using the genotype dosages that are part of the imputation algorithms output , with adjustments for admixture in the african american and latino case - control samples ( see supplementary note online ) . the shared summary files contained the snp identifiers ( rs number , chromosome , position , alleles ) , snp qc metrics ( call rate , hardy - weinberg equilibrium p - value , imputation quality metrics ) , and information related to the test for association ( allele frequencies in cases and controls or in the transmitted and untransmitted alleles in trios , association p - value , odds ratios with standard errors ) . reference alleles were assigned as the allele coded 0 in the hapmap release 21 phased consensus haplotypes during genotype imputation in mach . the qc checks performed on summary file data included consistency in reference allele and strand orientation ( see supplementary figs . 1315 online ) , and imputation quality ( see supplementary fig . 16 online ) . snps with imputation quality scores below a threshold were removed from the analysis ( rsq < 0.3 or < 0.5 for the barbados study ) . qq plots were visually inspected to compare the distribution of association p - values for genotyped and imputed markers separately for each cohort . the meta - analysis searched for asthma susceptibility variants for which the same allele was associated with asthma in the different studies . for each study , we constructed a test statistic that has a standard normal distribution under the null hypothesis of no association and captures the direction of the effect ( i.e. , the statistic was positive if the reference allele was associated with an increased risk of asthma ) . the meta - analysis test statistic was calculated as a linear combination of the individual study scores with weights proportional to the square root of the number of cases ( or trios ) . odds ratios were calculated by combining linearly log odds ratios with weights reflecting the standard errors from the genome - wide association studies . detailed descriptions of these samples , genotyping technologies , qc protocols , and statistical analyses are described in the supplementary note online . the combined analysis of the replication samples was performed in a similar manner to the meta - analysis . for each study , we constructed a test statistic that had standard normal distribution under the null hypothesis of no association , and that also captured the direction of the effect . a combined test statistic was calculated as a linear combination of the individual study scores with weights proportional to the square root of the number of cases , and p - values were obtained using normal approximations . pilot data from the 1000 genomes project ( august 2010 haplotypes ) was used to impute a 2 mb region surrounding the pyhin1 gene in all studies using impute2 . the eur haplotypes ( european ) were used as a reference for the european american studies ( assuming an effective population size [ ne ] of 11418 ) , the eur and afr ( african ) haplotypes were used as a reference for the african american studies ( assuming ne=15000 ) , and the eur , afr , and asn ( asian haplotypes ) were used as a reference for the latino studies ( assuming ne=15000 ) . individual genotypes were filtered for probabilities > 90% , and only snps with call rates > 90% were included in allelic tests of association . for family - based studies , snps with mendelian errors
asthma is a common disease with a complex risk architecture including both genetic and environmental factors . 
 we performed a meta - analysis of north american genome - wide association studies ( gwas ) of asthma in 5,416 asthma cases representing european americans , african americans / african caribbeans , and latinos , and replicated five regions among the most significant signals in 12,649 individuals from the same ethnic groups . 
 four were at previously reported loci on 17q21 , and near the il1rl1 , tslp , and il33 , genes , but we report for the first time that these loci are associated with asthma risk in three ethnic groups . in addition , we identified a novel association with asthma in the pyhin1 , gene that was specific to individuals of african descent ( p=3.9109 ) . 
 these results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated , and that ancestry - specific associations also contribute to the complex genetic architecture of asthma .