Genotyping Quality Control and Filtering

Genotyping in GERA was performed on the Affymetric Axion Genotyping System and underwent standard quality control procedures as previously described.^{8 (link)} Subjects in the MGB Biobank were genotyped on the Illumina Multi-Ethnic Global Array (MEGA), Expanded MEGA (MEGA Ex), and MEGA with imputation to the 1000 Genomes phase 3 reference panel using the Michigan Imputation Server.^{14 (link)} Genotyping was performed using the Illumina HumanHap550-Duo and Human 610-Quad BeadChips in the Rotterdam Study. Single-nucleotide polymorphisms (SNPs) with minor allele frequencies<1% and Hardy-Weinberg equilibrium exact test p<10⁻⁵ were filtered using Plink V.1.9.^{15 (link)} Identity-by-descent estimates were calculated in each cohort, and one subject from each pair with an identity-by-descent estimate >0.1875 was removed. In GERA, the final dataset comprised 8 995 492 and 9 004 920 variants, respectively, for the OCS burst (online supplemental figure 1) and asthma-related exacerbation (online supplemental figure 2) phenotypes.