Table 1. Association between top SNPs and lung function in males and females, and genotype-by-sex interaction results.
| SNP (nearest
gene) and coordinates |
Test/
other allele |
Trait | Lung function UK Biobank
males |
Lung function UK Biobank
females |
Sex interaction in UK
Biobank |
Sex interaction in
SpiroMeta |
||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MAF | Beta (SE) | P | MAF | Beta (SE) | P | Beta (SE) | P | Beta (SE) | P | |||
| rs7697189 (HHIP)
4:145436894 |
C/G | FEV 1 | 0.390 | 0.052 (0.004) | 2.13E-33 | 0.392 | 0.013 (0.003) | 1.16E-05 | -0.040 (0.005) | 3.15E-15 | -0.025 (0.01) | 0.016 |
| rs9403386 (ADGRG6)
6:142764073 |
C/A | FEV 1/FVC | 0.031 | 0.214 (0.012) | 4.48E-75 | 0.031 | 0.128 (0.009) | 2.16E-43 | -0.086 (0.015) | 4.56E-09 | -0.035 (0.032) | 0.281 |
| rs162185 (TCF21)
6:134226147 |
C/T | PEF | 0.411 | -0.038 (0.004) | 1.35E-18 | 0.410 | -0.009 (0.003) | 0.002 | 0.030 (0.005) | 4.87E-09 | 0.022 (0.0139) | 0.083 |
| rs6480592 (CHST3)
10:73764509 |
C/T | PEF | 0.398 | -0.021 (0.004) | 1.66E-06 | 0.400 | 0.007 (0.003) | 0.011 | 0.028 (0.005) | 2.85E-08 | 0.003 (0.012) | 0.808 |
| rs111893604 (ZSCAN10)
16:3141104 |
G/T | FEV 1 | 0.059 | 0.040 (0.009) | 1.70E-05 | 0.059 | -0.020 (0.006) | 0.002 | -0.060 (0.011) | 4.04E-08 | 0.006 (0.026) | 0.827 |
| rs72694266
(RP11-907D1.1) 14:97578576 |
A/C | PEF | 0.077 | -0.044 (0.008) | 2.69E-07 | 0.078 | 0.008 (0.006) | 0.145 | 0.053 (0.010) | 6.31E-08 | -0.049 (0.027) | 0.066 |
| rs72781459
10:10247676 |
C/T | PEF | 0.096 | 0.031 (0.007) | 3.44E-05 | 0.097 | -0.012 (0.005) | 0.014 | -0.046 (0.009) | 1.08E-07 | 0.007 (0.021) | 0.729 |
| rs74316059
(RP11-649A16.1) 3:146983325 |
T/C | FEV 1/FVC | 0.042 | 0.049 (0.010) | 2.52E-06 | 0.043 | -0.018 (0.008) | 0.029 | -0.068 (0.013) | 2.38E-07 | -0.031 (0.028) | 0.269 |
| rs55789572 (EIF2S2/RALY) 20:32687822 | A/C | FEV 1 | 0.022 | 0.041 (0.015) | 0.006 | 0.022 | -0.047 (0.010) | 2.67E-06 | -0.089 (0.017) | 2.80E-07 | -0.01 (0.033) | 0.765 |
| rs74933518 (DAPK2)
15:64303295 |
A/G | PEF | 0.025 | -0.072 (0.014) | 1.23E-07 | 0.025 | 0.007 (0.009) | 0.421 | 0.082 (0.016) | 3.05E-07 | 0.025 (0.043) | 0.568 |
| rs11247571 (ABR)
17:908502 |
G/A | PEF | 0.343 | -0.025 (0.005) | 3.65E-08 | 0.344 | 0.002 (0.003) | 0.569 | 0.027 (0.005) | 3.22E-07 | 0.010 (0.014) | 0.473 |
| rs707588
(RP11-154H17.1) 1:5711430 |
G/A | FEV 1 | 0.482 | -0.020 (0.004) | 3.23E-06 | 0.482 | 0.006 (0.003) | 0.029 | 0.025 (0.005) | 3.27E-07 | 0.014 (0.01) | 0.183 |
| rs138473298 (AUTS2)
7:69644989 |
T/C | PEF | 0.012 | -0.077 (0.020) | 0.0002 | 0.011 | 0.043 (0.014) | 0.002 | 0.122 (0.024) | 3.52E-07 | 0.037 (0.060) | 0.540 |
| rs139069254
(RP11-648K4.2) 15:88113916 |
A/G | FEV 1 | 0.018 | 0.071 (0.016) | 1.83E-05 | 0.018 | -0.027 (0.011) | 0.017 | -0.098 (0.019) | 4.66E-07 | -0.051 (0.041) | 0.216 |
| rs138163836 (PVRL3)
3:110952902 |
C/T | FVC | 0.021 | 0.064 (0.015) | 1.94E-05 | 0.020 | -0.025 (0.011) | 0.019 | -0.091 (0.018) | 5.07E-07 | -0.025 (0.038) | 0.5 |
| rs28493055 (XDH)
2:31573390 |
T/G | FEV 1 | 0.012 | 0.065 (0.020) | 0.002 | 0.013 | -0.055 (0.014) | 6.40E-05 | -0.119 (0.024) | 5.60E-07 | 0.035 (0.054) | 0.519 |
| rs117380804
18:76145905 |
T/C | FVC | 0.035 | 0.035 (0.012) | 0.003 | 0.036 | -0.035 (0.008) | 1.93E-05 | -0.070 (0.014) | 6.25E-07 | -0.034 (0.03) | 0.255 |
| rs602622 (RASGRP3)
2:33658226 |
C/G | PEF | 0.444 | -0.022 (0.004) | 2.11E-07 | 0.445 | 0.002 (0.003) | 0.444 | 0.025 (0.005) | 6.45E-07 | -0.013 (0.013) | 0.323 |
| rs2253718
(RF00019, SFTA2) 6:30900427 |
T/G | PEF | 0.409 | -0.049 (0.004) | 5.69E-30 | 0.405 | -0.027 (0.003) | 1.78E-20 | 0.025 (0.005) | 7.05E-07 | 0.002 (0.016) | 0.925 |
| rs2353939 (HHIP)
4:145729724 |
G/A | FVC | 0.437 | 0.016 (0.004) | 0.0002 | 0.435 | -0.009 (0.003) | 0.002 | -0.025 (0.005) | 7.55E-07 | -0.016 (0.01) | 0.124 |
| rs7691139 (ZNF280A)
22:22876151 |
G/C | FEV 1/FVC | 0.116 | -0.025 (0.007) | 0.0003 | 0.115 | 0.017 (0.005) | 0.002 | 0.043 (0.009) | 7.62E-07 | Not tested | |
| rs13020954
2:17296984 |
C/T | FEV 1/FVC | 0.014 | 0.050 (0.017) | 0.004 | 0.014 | -0.057 (0.014) | 3.83E-05 | -0.109 (0.022) | 7.88E-07 | -0.062 (0.043) | 0.148 |
| rs2731120 (MLF1)
3:158297633 |
A/C | FVC | 0.346 | 0.029 (0.004) | 3.72E-11 | 0.346 | 0.003 (0.003) | 0.310 | -0.026 (0.005) | 8.14E-07 | -0.008 (0.011) | 0.433 |
| rs355079
(LMCD1-AS1) 3:8643371 |
T/C | FVC | 0.337 | 0.015 (0.004) | 0.0007 | 0.339 | -0.011 (0.003) | 0.0004 | -0.026 (0.005) | 8.84E-07 | 0.001 (0.011) | 0.935 |
| rs7338055 (SPRYD7)
13:50504226 |
C/A | FVC | 0.259 | 0.018 (0.005) | 0.0001 | 0.259 | -0.009 (0.003) | 0.008 | -0.028 (0.006) | 9.81E-07 | -0.008 (0.012) | 0.478 |
| rs34490170 (NEUROD1/
CERKL) 2:182576419 |
C/T | FVC | 0.110 | -0.035 (0.007) | 6.41E-07 | 0.110 | 0.007 (0.005) | 0.186 | 0.041 (0.008) | 9.95E-07 | 0.009 (0.018) | 0.622 |
The SNPs are those that demonstrate a sex-interaction effect on lung function in UK Biobank (P<1x10 -6) (N = 303,612). Lung function traits were pre-adjusted for age, age 2, standing height and smoking status and the residuals rank-transformed to normality. The regression models also included genotyping array and the first ten ancestry-based principal components. For each SNP, columns 4-9 provide minor allele frequency (MAF), and beta-coefficients, standard errors and the P value for their association with lung function in males and females separately. Columns 10-11 show the results of the SNP-by-sex interaction in UK Biobank, where the effect is given in females relative to males. For example, the top SNP (rs7697189) shows a less positive effect in females compared to males and its beta coefficient is therefore negative. Columns 12-13 show the results of the SNP-by-sex interaction in 20 cohorts of the SpiroMeta consortium (N = 75,696). Bold text in final column indicates that the effect in SpiroMeta was in the same direction to the effect in UK Biobank.