For FEV1/FVC, among 18 SNPs tested for replication, six SNPs in three loci were significantly associated with this measure in SpiroMeta: rs1980057 and rs1032295 near HHIP (r2=0.72), rs2070600 in AGER and rs10947233 in PPT2 (r2=0.66), and rs11168048 and rs7735184 in HTR4 (r2=0.93) (Table 2). Their joint meta-analysis P values ranged from 3.21×10−20 to 6.23×10−11 (Table 2). Five additional SNPs in GPR126 (rs3817928, rs7776375, and rs6937121) and ADAM19 (rs2277027 and rs1422795) were not significantly associated with FEV1/FVC at the stringent threshold in SpiroMeta, but these SNPs were associated at genome-wide significance in the joint meta-analysis with P values ranging from 9.93×10−11 to 1.25×10−8 (Table 2). For replicated SNPs, the allele frequencies and the direction and magnitude of the associations with FEV1/FVC were similar between consortia (Table 2). Further, the HHIP, ADAM19, and HTR4 SNPs were significantly associated with FEV1 in SpiroMeta (Supplementary Table 5). The HHIP SNP rs1980057 and HTR4 SNPs rs11168048 and rs7735184 were also associated with FEV1 at genome-wide significance in the joint meta-analysis (P ranging from 5.86×10−9 to 1.58×10−8, Supplementary Table 5). SNPs in FAM13A, PTCH1, and PID1 that gave genome-wide significance in CHARGE were not confirmed in analyses with SpiroMeta.
