Table 1.
Loci associated with lung function. Shown are FEV1 and FEV1/FVC results for the leading SNPs, ordered by chromosome and position, for each independent locus associated (P <5×10−8) with FEV1 or FEV1/FVC in a joint analysis of up to 94,612 individuals of European ancestry from the SpiroMeta-CHARGE GWAS (Stage 1) and follow-up (Stage 2). Two-sided p-values are given for Stage 1, Stage 2 and the joint meta-analysis of all stages. P-values reaching genome-wide significance (P<5×10−8) in the joint meta-analysis of all stages are indicated in bold. SNPs reaching independent replication in Stage 2 (P=0.05/34 = 1.47×10−3) are indicated with their Stage 2 p-value in bold. The sample sizes (N) shown are the effective sample sizes. Effective sample size within each study is the product of sample size and imputation quality metric. Joint meta-analysis includes data from Stage 1 and Stage 2. Beta values reflect effect-size estimates on an inverse-normal transformed scale after adjustments for age, age2, sex, height and ancestry principal components. The estimated proportion of the variance explained by each SNP can be found in Supplementary Table 6.
| Chr. | SNP_ID(NCBI36 position), function | Coded allele freq. |
Measure | Stage 1 | Stage 2 | Joint meta-analysis of all stages |
|||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Beta (s.e.m.) | P | Coded allele freq. |
N | Beta (s.e.m.) | P | Coded allele freq. |
N | Beta (s.e.m.) | P | ||||
| 1 | rs2284746(17179262), MFAP2(intron) | G | FEV1/FVC | −0.042 (0.007) | 2.47E-09 | 0.516 | 45944 | −0.038 (0.007) | 2.64E-07 | 0.522 | 35371 | −0.04 (0.005) | 7.50E-16 |
| FEV1 | 0.008 (0.007) | 2.78E-01 | 0.006 (0.007) | 3.70E-01 | 0.007 (0.005) | 1.48E-01 | |||||||
| 1 | rs993925(216926691), TGFB2(downstream) | T | FEV1/FVC | 0.04 (0.007) | 2.54E-07 | 0.308 | 42402 | 0.023 (0.01) | 1.76E-02 | 0.348 | 21414 | 0.034 (0.006) | 1.16E-08 |
| FEV1 | 0.025 (0.007) | 1.51E-03 | 0.003 (0.007) | 7.29E-01 | 0.014 (0.005) | 8.71E-03 | |||||||
| 2 | rs12477314(239542085), HDAC4(downstream) | T | FEV1/FVC | 0.052 (0.008) | 4.48E-09 | 0.202 | 45585 | 0.031 (0.008) | 8.41E-05 | 0.206 | 45821 | 0.041 (0.006) | 1.68E-12 |
| FEV1 | 0.032 (0.008) | 2.77E-04 | 0.025 (0.007) | 1.82E-04 | 0.028 (0.005) | 1.02E-07 | |||||||
| 3 | rs1529672(25495586), RARB(intron) | C | FEV1/FVC | −0.06 (0.009) | 7.75E-10 | 0.829 | 40624 | −0.038 (0.009) | 1.16E-05 | 0.831 | 45466 | −0.048 (0.006) | 3.97E-14 |
| FEV1 | −0.037 (0.009) | 1.78E-04 | −0.011 (0.007) | 9.33E-02 | −0.02 (0.006) | 2.16E-04 | |||||||
| 3 | rs1344555(170782913), MECOM(intron) | T | FEV1/FVC | −0.019 (0.008) | 2.61E-02 | 0.205 | 46067 | −0.017 (0.012) | 1.55E-01 | 0.209 | 21313 | −0.018 (0.007) | 6.65E-03 |
| FEV1 | −0.042 (0.008) | 1.91E-06 | −0.025 (0.009) | 6.44E-03 | −0.034 (0.006) | 2.65E-08 | |||||||
| 5 | rs153916(95062456), SPATA9(upstream) | T | FEV1/FVC | −0.033 (0.007) | 2.06E-06 | 0.552 | 47530 | −0.025 (0.009) | 6.67E-03 | 0.535 | 21647 | −0.031 (0.005) | 2.12E-08 |
| FEV1 | −0.001 (0.007) | 8.91E-01 | 0.004 (0.007) | 6.22E-01 | 0.001 (0.005) | 8.20E-01 | |||||||
| 6 | rs6903823(28430275), ZKSCAN3(intron)/ZNF323(intron) | G | FEV1/FVC | −0.027 (0.008) | 2.28E-03 | 0.209 | 47057 | −0.013 (0.011) | 2.34E-01 | 0.246 | 21489 | −0.021 (0.007) | 1.19E-03 |
| FEV1 | −0.046 (0.008) | 2.00E-07 | −0.029 (0.008) | 4.75E-04 | −0.037 (0.006) | 2.18E-10 | |||||||
| 6 | rs2857595(31676448), NCR3(upstream) | G | FEV1/FVC | 0.049 (0.009) | 7.86E-08 | 0.809 | 45540 | 0.028 (0.008) | 5.36E-04 | 0.796 | 46107 | 0.037 (0.006) | 2.28E-10 |
| FEV1 | 0.04 (0.009) | 1.46E-05 | 0.017 (0.007) | 9.41E-03 | 0.025 (0.005) | 1.30E-06 | |||||||
| 6 | rs2798641(109374743), ARMC2(intron) | T | FEV1/FVC | −0.047 (0.009) | 2.81E-07 | 0.183 | 46369 | −0.03 (0.012) | 1.57E-02 | 0.179 | 21173 | −0.041 (0.007) | 8.35E-09 |
| FEV1 | −0.046 (0.009) | 5.39E-07 | −0.009 (0.01) | 3.35E-01 | −0.03 (0.006) | 4.69E-06 | |||||||
| 10 | rs7068966(12317998), CDC123(intron) | T | FEV1/FVC | 0.045 (0.007) | 1.28E-10 | 0.519 | 47085 | 0.023 (0.006) | 3.86E-04 | 0.518 | 46067 | 0.033 (0.005) | 6.13E-13 |
| FEV1 | 0.04 (0.007) | 1.19E-08 | 0.022 (0.005) | 3.56E-05 | 0.029 (0.004) | 2.82E-12 | |||||||
| 10 | rs11001819(77985230), C10orf11(intron) | G | FEV1/FVC | −0.019 (0.007) | 6.50E-03 | 0.522 | 45546 | −0.006 (0.006) | 3.17E-01 | 0.506 | 45932 | −0.012 (0.005) | 7.58E-03 |
| FEV1 | −0.041 (0.007) | 1.42E-08 | −0.022 (0.005) | 3.10E-05 | −0.029 (0.004) | 2.98E-12 | |||||||
| 12 | rs11172113(55813550), LRP1(intron) | T | FEV1/FVC | −0.035 (0.007) | 1.36E-06 | 0.607 | 45387 | −0.026 (0.01) | 5.83E-03 | 0.59 | 20509 | −0.032 (0.006) | 1.24E-08 |
| FEV1 | −0.021 (0.007) | 3.55E-03 | −0.003 (0.007) | 6.94E-01 | −0.013 (0.005) | 1.19E-02 | |||||||
| 12 | rs1036429(94795559), CCDC38(intron) | T | FEV1/FVC | 0.049 (0.008) | 1.24E-08 | 0.2 | 47814 | 0.028 (0.008) | 3.35E-04 | 0.214 | 46311 | 0.038 (0.006) | 2.30E-11 |
| FEV1 | 0.01 (0.008) | 2.67E-01 | 0.004 (0.006) | 5.38E-01 | 0.006 (0.005) | 2.26E-01 | |||||||
| 16 | rs12447804(56632783), MMP15(intron) | T | FEV1/FVC | −0.053 (0.009) | 7.12E-08 | 0.208 | 35123 | −0.021 (0.01) | 4.20E-02 | 0.222 | 24398 | −0.038 (0.007) | 3.59E-08 |
| FEV1 | −0.017 (0.009) | 8.02E-02 | 0.004 (0.007) | 5.71E-01 | −0.004 (0.006) | 4.73E-01 | |||||||
| 16 | rs2865531(73947817), CFDP1(intron) | T | FEV1/FVC | 0.039 (0.007) | 2.30E-08 | 0.418 | 47594 | 0.024 (0.006) | 1.94E-04 | 0.409 | 46304 | 0.031 (0.005) | 1.77E-11 |
| FEV1 | 0.024 (0.007) | 6.30E-04 | 0.011 (0.005) | 3.89E-02 | 0.016 (0.004) | 1.09E-04 | |||||||
| 21 | rs9978142(34574109), KCNE2(upstream) | T | FEV1/FVC | −0.048 (0.009) | 8.23E-07 | 0.156 | 44577 | −0.031 (0.013) | 1.75E-02 | 0.149 | 20944 | −0.043 (0.008) | 2.65E-08 |
| FEV1 | −0.012 (0.009) | 2.47E-01 | −0.015 (0.01) | 1.35E-01 | −0.013 (0.007) | 5.57E-02 | |||||||