Table 2.
The validation study to test for 11 genes transcriptomic and methylomic expression level associations with prostate cancer at a FDR-corrected significance level
| Associations in TWAS | Genes showing differential expression in tumor vs normal prostate samples |
CpG sites showing significant differential methylation levels between prostate tumor and tumor adjacent normal samples |
Biologically significant differential methylation levels between prostate tumor and tumor adjacent normal samples |
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|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Gene Name | region | Classification | R2a | OR (95%CI) | P-value | P-value after FDRa | model | FC b | P-value after FDR b | Probe ID | FC b | P-value after FDR b | P-value after FDR b | P-valueb | r b | |
| ADAM15 | 1q22 | protein_coding | 0.02 | 1.35 (1.23-1.48) | 1.59×10−10 | 3.23×10−8 | JTI | 1.36 | 4.51×10−8 | cg13069100 | 1.48 | 5.35×10−22 | 3.31×10−5 | 1.75×10−6 | 0.72 | Pearson |
| 0.05 | 1.23 (1.16-1.3) | 1.94×10−11 | 4.57×10−9 | PrediXcan | ||||||||||||
| LDAH | 2p24.1 | protein_coding | 0.05 | 0.8 (0.75-0.85) | 3.45×10−12 | 9.09×10−10 | JTI | −1.73 | 2.84×10−11 | cg20248458 | 2.00 | 6.36×10−13 | 0.02 | 1.65×10−3 | −0.52 | Pearson |
| 0.13 | 0.9 (0.88-0.93) | 1.25×10−12 | 3.48×10−10 | PrediXcan | ||||||||||||
| 0.13 | 0.87 (0.83-0.9) | 4.71×10−15 | 1.78×10−12 | Modified UTMOST | ||||||||||||
| AMT | 3p21.31 | protein_coding | 0.33 | 0.95 (0.92-0.97) | 5.42×10−5 | 3.10×10−3 | Modified UTMOST | −1.87 | 3.42×10−12 | cg02251567 | 1.70 | 4.13×10−20 | 1.65×10−7 | 1.10×10−9 | −0.83 | Pearson |
| cg05924489 | 2.17 | 3.73×10−20 | 5.23×10−7 | 1.38×10−8 | −0.80 | Pearson | ||||||||||
| 0.35 | 0.96 (0.94-0.98) | 5.24×10−5 | 3.02×10−3 | PrediXcan | cg14184400 | 1.66 | 9.00×10−19 | 5.23×10−7 | 3.51×10−7 | −0.80 | Pearson | |||||
| cg15246085 | 1.74 | 2.65×10−20 | 5.23×10−7 | 2.40×10−7 | −0.80 | Pearson | ||||||||||
| 0.32 | 0.95 (0.93-0.97) | 1.81×10−5 | 1.22×10−3 | JTI | cg17877071 | 1.56 | 3.62×10−19 | 8.34×10−7 | 2.91×10−7 | −0.79 | Pearson | |||||
| cg20191453 | 1.71 | 1.23×10−17 | 8.34×10−7 | 3.31×10−8 | −0.79 | Pearson | ||||||||||
| cg21926782 | 1.45 | 4.80×10−17 | 1.07×10−6 | 3.51×10−7 | −0.78 | Pearson | ||||||||||
| UBA7 | 3p21.31 | protein_coding | 0.07 | 0.84 (0.76-0.94) | 1.62×10−3 | 0.04 | Modified UTMOST | −1.26 | 6.88×10−5 | cg13343687 | 1.59 | 3.16×10−20 | 0.04 | 3.76×10−3 | −0.48 | Pearson |
| SRGAP3 | 3p25.3 | protein_coding | 0.03 | 0.88 (0.81-0.95) | 1.05×10−3 | 0.03 | Modified UTMOST | −1.15 | 0.04 | cg12669543 | 1.72 | 2.20×10−17 | 0.02 | 2.42×10−3 | −0.50 | Pearson |
| 0.04 | 0.88 (0.81-0.95) | 1.04×10−3 | 0.03 | PrediXcan | ||||||||||||
| ATF6B | 6p21.33 | protein_coding | 0.12 | 1.07 (1.03-1.12) | 5.92×10−4 | 0.02 | Modified UTMOST | 1.07 | 0.03 | cg09149894 | −1.15 | 9.65×10−4 | 0.03 | 3.42×10−3 | −0.49 | Pearson |
| 0.13 | 1.07 (1.04-1.1) | 3.60×10−5 | 2.19×10−3 | PrediXcan | ||||||||||||
| 0.03 | 1.17 (1.09-1.26) | 2.67×10−5 | 1.71×10−3 | JTI | ||||||||||||
| VARS2 | 6p21.33 | protein_coding | 0.44 | 1.05 (1.03-1.07) | 6.49×10−7 | 6.78×10−5 | JTI | 1.42 | 3.01×10−10 | cg00933603 | −1.08 | 0.02 | 6.34×10−5 | 3.78×10−6 | −0.70 | Pearson |
| 0.43 | 1.06 (1.03-1.08) | 2.99×10−7 | 3.39×10−5 | Modified UTMOST | ||||||||||||
| 0.47 | 1.05 (1.03-1.07) | 1.05×10−7 | 1.35×10−5 | PrediXcan | ||||||||||||
| SMYD4 | 17p13.3 | protein_coding | 0.12 | 0.92 (0.88-0.96) | 4.34×10−4 | 0.02 | JTI | −1.38 | 6.71×10−9 | cg16616918 | 1.46 | 5.91×10−14 | 9.36×10−5 | 6.20×10−6 | −0.69 | Pearson |
a
R2: prediction performance (R2) derived using GTEx data. P value: derived from association analyses of 79,194 cases and 61,112 controls; associations with FDR-corrected P value < 0.05 considered significant.
b
P value: derived from 34 prostatic tumor tissue samples and paired normal prostatic tissue samples.