Table 2.
Summary of associations between the 12 SNPs and risk for gene methylation in the LSC and PLuSS studies
| SNP | Chr | Position* | Allele† | MAF‡ | Gene/RNA | LSC (stage 1)§ | PLuSS (stage 2)|| | Combined¶ | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| P | OR (95% CI) | P | OR (95% CI) | P | OR (95% CI) | ||||||
| rs7604698 | 2 | 180078742 | C/A | 0.24 | ZNF385B | 1.83×10–6 | 1.25 (1.14 to 1.38) | .32 | 1.09 (0.92 to 1.29) | — | — |
| rs4459923 | 3 | 151685713 | G/A | 0.40 | TSC22D2 | 7.48×10–7 | 1.24 (1.14 to 1.35) | .27 | 1.09 (0.94 to 1.27) | — | — |
| rs4447788# | 3 | 151701304 | T/C | 0.30 | TSC22D2 | 2.03×10–6 | 1.24 (1.13 to 1.35) | .62 | 1.04 (0.89 to 1.22) | — | — |
| rs2398721 | 5 | 143568607 | C/T | 0.22 | KCTD16 | 4.45×10–6 | 1.28 (1.15 to 1.42) | .99 | 1.00 (0.85 to 1.18) | — | — |
| rs12414981 | 10 | 122732922 | A/G | 0.11 | MIR5694 | 4.85×10–6 | 0.72 (0.63 to 0.83) | .32 | 1.12 (0.90 to 1.38) | — | — |
| rs4751287 | 10 | 132559608 | T/G | 0.49 | MIR378C | 4.30×10–6 | 1.21 (1.12 to 1.31) | .57 | 0.96 (0.84 to 1.11) | — | — |
| rs1580746 | 12 | 86538292 | G/A | 0.39 | MKRN9P | 2.14×10–6 | 1.24 (1.13 to 1.35) | .94 | 1.01 (0.86 to 1.17) | — | — |
| rs73371737 | 15 | 23335869 | C/A | 0.11 | UBE3A | 2.86×10–6 | 1.34 (1.19 to 1.51) | .0076 | 1.37 (1.09 to 1.72) | 3.3×10–8 | 1.35 (1.21 to 1.50) |
| rs7179575** | 15 | 24905945 | C/T | 0.36 | GABRG3 | 1.79×10–5 | 0.82 (0.75 to 0.90) | .058 | 0.87 (0.75 to 1.00) | 3.8×10–6 | 0.83 (0.77 to 0.90) |
| HapAC†† | 0.07 | 1.07×10–6 | 1.79 (1.26 to 2.54) | .0012 | 1.57 (1.35 to 1.82) | 2.5×10–9 | 1.57 (1.35 to 1.82) | ||||
| rs16946867 | 18 | 4460922 | G/A | 0.17 | DLGAP1 | 6.10×10–7 | 0.74 (0.66 to 0.83) | .76 | 0.97 (0.81 to 1.17) | — | — |
| rs767457 | 20 | 22133332 | T/C | 0.36 | CR627206 | 4.16×10–6 | 1.22 (1.12 to 1.33) | .59 | 0.96 (0.83 to 1.11) | — | — |
| rs62202801‡‡ | 20 | 22190904 | C/T | 0.35 | CR627206 | 3.00×10–6 | 1.24 (1.13 to 1.35) | .30 | 0.93 (0.80 to 1.07) | — | — |
* Based on genome build 36. Statistical tests were two-sided. Chr = chromosome; CI = confidence interval; LSC = the Lovelace Smokers Cohort; MAF = minor allele frequency; OR = odds ratio; PLuSS = the Pittsburgh Lung Screening Study cohort; SNP = single nucleotide polymorphism.
† Allele after ‘/’ is the test allele and minor allele.
‡ MAF is from the LSC set. MAF from the PLuSS set shows minimal difference compared with that seen in LSC.
§ Age, sex, current smoking status, and pack-years were included in the generalized estimating equation models for adjustment.
|| Age, sex, current smoking status, pack-years, and pulmonary function were included in the generalized estimating equation models for adjustment.
¶ Meta-analysis was conducted for two 15q12 SNPs and HapAC only.
# R2 is 0.52 with rs4459923.
** R2 is 0.000098 with rs73371737.
†† HapAC is the haplotype allele A-C for rs73371737 and rs7179575 on chromosome 15. The MAF for HapAC is population haplotype frequency estimated using PHASE. Probability for haplotype alleles other than AC was used as reference for comparison. The full results for haplotype-based analysis between rs73371737 and rs7179575 are in Supplementary Table 5 (available online).
‡‡ R2 is 0.69 with rs767457.