Table 1:
Sentinel variants of novel associations.
| Chr | Position | rsid | Annotation | Ref allele | Effect allele | EAF | Direction | Study p≤0.05 | OR [95% CI] | p | PPR |
|---|---|---|---|---|---|---|---|---|---|---|---|
| i) Novel variants with high posterior probability of replication (PPR≥90%) | |||||||||||
| 10 | 111229861 | rs79684490 | Intergenic (10q25.1) | G | A | 4.6% | + + + + + | YYNYY | 1.40 [1.24, 1.57] | 3.52×10−8 | 94.0% |
| 15 | 40931708 | rs12912339 a | Intron of KNL1 | G | A | 15.9% | + + + + + | YYNYY | 1.30 [1.21, 1.39] | 7.41×10−13 | 96.5% |
| 16 | 162240 | rs74614704 | Intron of NPRL3 | G | A | 5.6% | + + + + + | YNNYY | 1.49 [1.33, 1.67] | 2.57×10−12 | 99.4% |
| 20 | 62284170 | rs112087793 b | Intron of STMN3 | T | C | 91.5% | + + + + + | YYYYY | 1.34 [1.21, 1.48] | 1.09×10−8 | 96.8% |
| 20 | 62324391 | rs41308092 b | Intron of RTEL1 | G | A | 2.1% | + + + + + | YYYYN | 1.75 [1.45, 2.10] | 3.13×10−9 | 99.9% |
| ii) Novel variants not reaching PPR≥90% threshold | |||||||||||
| 1 | 214659598 | rs4233306 | Intron of PTPN14 | T | C | 80.2% | + + + + + | YYNNN | 1.23 [1.15, 1.32] | 3.41×10−9 | 37.4% |
| 6 | 43352980 | rs1214759 | Intergenic (6p21.2) | A | G | 67.9% | + + + + + | NYYYN | 1.18 [1.11, 1.25] | 1.71×10−8 | 21.9% |
| 9 | 109480268 | rs11788059 | Regulatory region variant (9q31.2) | T | C | 34.2% | + + + + + | NYNYY | 1.17 [1.10, 1.23] | 4.85×10−8 | 3.1% |
| 10 | 105640978 | rs7100920 | Regulatory region of OBFC1 | C | T | 49.0% | + + − + + | NYNYY | 1.19 [1.13, 1.26] | 1.67×10−10 | 32.1% |
Novel variants are defined as those not reaching significance criteria in previous analysis2 (the RTEL1 and OBFC1 signals have previously shown a possible association – see discussion). Effect sizes and directions are given in terms of the allele that increases risk of IPF. Chr=Chromosome. Position is based on genetic build 37. Annotation obtained from Variant Effect Predictor12. EAF=Effect allele frequency calculated across the five studies. The “Direction” column shows the direction of the beta in each of the five individual studies (+ means beta>0, − means beta<0). The “Study p≤0.05” column denotes which individual studies the variant reached nominal significance in (Y means p≤0.05, N means p>0.05). Both the direction and study p<0.05 are given in the order UK, Colorado, Chicago, UUS and then Genentech. OR=Odds ratio. CI=Confidence interval. PPR=posterior probability of replicability calculated using MAMBA13.
The signal at KNL1 is independent of the previously reported nearby signal in the IVD gene.
The RTEL1 and STMN3 signals are independent of each other.