Table 2.
Signals that achieved the significance threshold in GWAS for associations with age-at-onset of familial PD
| CHR | Gene | SNP | MAF | Discovery (NGRC) |
Replication |
Discovery + Replication |
||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| GWAS Test Cox regression |
Effect on AAO Linear regression |
Test Cox regression |
Effect on AAO Linear regression |
Test Cox regression |
Effect on AAO Linear regression |
|||||||||||||
| HR | P | Beta | 95% CI | P | HR | P | Beta | 95% CI | P | HR | P | Beta | 95% CI | P | ||||
| 5 | LHFPL2 | rs10035651 | 0.016 | 4.76 | 3E-8 | ‐12.31 | ‐18.42; -6.19 | 8E-5 | – | – | – | – | – | – | – | – | – | – |
| 5 | LHFPL2 | rs344650 | 0.016 | 4.77 | 3E-8 | ‐12.33 | ‐18.45; -6.21 | 8E-5 | 2.68 | 2E-5 | ‐8.03 | ‐13.11; -2.95 | 1E-3 | 3.40 | 1E-11 | ‐9.79 | ‐13.70; -5.88 | 9E-7 |
| 5 | LHFPL2 | rs344657 | 0.016 | 4.77 | 3E-8 | ‐12.33 | ‐18.45; -6.21 | 8E-5 | – | – | – | – | – | – | – | – | – | – |
| 8 | TRPS1 | rs74335301 | 0.014 | 4.46 | 3E-8 | ‐11.76 | ‐17.98; -5.54 | 2E-4 | 1.39 | 0.07 | 0.44 | ‐4.34; 5.23 | 0.86* | 2.20 | 3E-6 | ‐4.09 | ‐7.89; -0.30 | 0.03 |
| 14 | KLHDC1 | rs79503702 | 0.012 | 6.95 | 7E-9 | ‐14.81 | ‐22.00; -7.62 | 5E-5 | 1.89 | 0.04 | ‐2.03 | ‐10.46; 6.41 | 0.32 | 3.82 | 5E-8 | ‐9.43 | ‐14.90; -3.96 | 7E-4 |
| 14 | KLHDC1_ARF6 | rs192855008 | 0.012 | 7.12 | 4E-9 | ‐15.01 | ‐22.22; -7.79 | 5E-5 | – | – | – | – | – | – | – | – | – | – |
| 15 | TPM1 | rs117267308 | 0.012 | 6.47 | 2E-8 | ‐15.30 | ‐22.49; -8.10 | 3E-5 | 3.20 | 2E-4 | ‐9.29 | ‐16.79; -1.79 | 8E-3 | 4.55 | 9E-11 | ‐12.42 | ‐17.61; -7.23 | 3E-6 |
| 15 | TPM1 | rs141049631 | 0.012 | 6.47 | 2E-8 | ‐15.30 | ‐22.49; -8.10 | 3E-5 | – | – | – | – | – | – | – | – | – | – |
| 15 | TPM1 | rs116860970 | 0.013 | 6.52 | 8E-9 | ‐15.13 | ‐22.17; -8.09 | 3E-5 | – | – | – | – | – | – | – | – | – | – |
| 15 | TPM1 | rs77362326 | 0.012 | 6.47 | 2E-8 | ‐15.30 | ‐22.49; -8.10 | 3E-5 | – | – | – | – | – | – | – | – | – | – |
| 15 | TPM1 | rs201411148 | 0.012 | 6.47 | 2E-8 | ‐15.30 | ‐22.49; -8.10 | 3E-5 | – | – | – | – | – | – | – | – | – | – |
| 15 | TPM1 | rs142383316 | 0.012 | 6.47 | 2E-8 | ‐15.30 | ‐22.49; -8.10 | 3E-5 | – | – | – | – | – | – | – | – | – | – |
| 15 | TPM1 | rs117484764 | 0.012 | 6.46 | 2E-8 | ‐15.29 | ‐22.49; -8.10 | 3E-5 | – | – | – | – | – | – | – | – | – | – |
SNPs that achieved P < 5E-8 in GWAS in familial PD are shown. They are in four LD blocks. One SNP per block was genotyped in additional samples of familial PD for replication. GWAS was conducted using Cox regression. Replication testing was conducted using Cox regression, and datasets were combined using Meta analysis. For data sets with 6 or fewer observations, Firth Penalization correction for Cox was applied. Similarly, tests for combined Discovery and Replication were conducted using Cox regression and Meta analysis. The effect on age-at-onset was calculated using linear regression. No SNPs achieved P < 5E-8 in non-familial PD or in all PD. For the list of signals that achieved P < 1E-6 see Table 3, and for genome-wide results see Supplementary Material, Tables S1–S3. CHR = chromosome, MAF = minor allele frequency, HR = age-specific Hazard Ratio calculated using Cox regression with its associated test P-value, Beta = years difference in age-at-onset per each allele (additive model) with its 95% confidence interval. – indicates not tested. Replication P values are one-sided, both for Cox and linear regression, *except for the linear regression result for rs74335301 because it was in opposite direction compared to discovery. P values for Discovery + Replication are all two-sided.