Table 2. Novel loci associated with lung function traits.
Results are shown for variant in novel loci associated (P<2·7×10 -7) with lung function traits in a two stage meta-analysis consisting of up to 68,470 individuals from the SpiroMeta and CHARGE Consortia in the discovery analyses, with follow-up in up to 111,556 individuals from UK Biobank, UKHLS and NEO. For each SNP, the result for the trait-smoking-ancestry combination which resulted in the most statistically significant association is given. The results for these SNPs and all three traits are shown in Supplementary Table 12. Beta values from SpiroMeta (β Sp) reflect effect-size estimates on an inverse-normal transformed scale after adjustments for age, age 2, sex, height and ancestry principal components, and stratified by ever smoking status (Analysis of All individuals only). Beta values from CHARGE (β CH) reflect effect-size estimates on an untransformed scale (litres for FEV 1 and FVC; ratio for FEV 1/FVC). Samples sizes (N), Z-statistics (Z) and two-sided P-values (P) are given for the combined discovery analysis and the replication analysis. Two-sided P-values are also given for the full two-stage combined analyses (discovery + replication).
| Consortium
results |
Combined discovery
meta-analysis |
Replication | Two-stage
combined |
|||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SNP | Chr:Pos | (Nearest) gene(s) | Trait | Smoking | Ancestry | Effect/other
allele |
Effect allele
frequency (Discovery) |
β CH | β Sp | N disc | Z disc | P disc | N rep | Z rep | P rep | P meta |
| rs2322659 | 2:136555659 | LCT (nonsynonymous) | FVC | All Individuals | EA Only | T/C | 23·5% | 27·34 | 0·032 | 55,591 | 5·597 | 2·18×10 -8 | 12,899 | 2·286 | 0·0223 | 1·70 ×10 -9 |
| rs1448044 | 5:44296986 |
FGF10(dist=8111),
NNT(dist=591,318) |
FVC | Ever Smokers | EA+AA | A/G | 35·6% | 18·63 | 0·057 | 30,966 | 4·813 | 1·49 ×10 -6 | 64,400 | 4·805 | 1·55 ×10 -6 | 2·22 ×10 -11 |
| rs1294421 | 6:6743149 |
LY86(dist=87,933),
RREB1(dist=364,681) |
FEV
1/
FVC |
All Individuals | EA+AA | T/G | 36·8% | -0·222 | -0·038 | 68,099 | -5·479 | 4·27 ×10 -8 | 111,556 | -8·171 | 3·06 ×10 -16 | 9·74 ×10 -23 |
| rs3849969 | 10: 75525999 | SEC24C (intronic) | FEV1 | All Individuals | EA+AA | T/C | 29·4% | 13·10 | 0·036 | 68,116 | 4·767 | 1·87 ×10 -6 | 111,556 | 5·042 | 4·60 ×10 -7 | 4·99 ×10 -12 |
| rs1200345 | 15: 41819716 | RPAP1 (nonsynonymous) | FEV1/
FVC |
All Individuals | EA only | C/T | 48·8% | -0·217 | -0·025 | 60,381 | -4·586 | 4·51 ×10 -6 | 111,556 | -5·725 | 1·03 ×10 -8 | 2·33 ×10 -13 |
| rs1859962 | 17: 69108753 | CASC17 (intronic) | FEV 1 | All Individuals | EA only | G/T | 48·2% | 15·39 | 0·026 | 60,395 | 4·876 | 1·08 ×10 -6 | 111,554 | 4·612 | 3·99 ×10 -6 | 4·10 ×10 -11 |
| rs6088813 | 20: 33975181 | UQCC1 (intronic) | FVC | All Individuals | EA+AA | C/A | 36·7% | -16·16 | -0·023 | 68,115 | -4·634 | 3·58×10 -6 | 111,556 | -7·688 | 1·50 ×10 -14 | 4·90 ×10 -19 |