Table 4: Stage two replication phase results.
Associations of genotyped common and rare, non-synonymous, and non-H1/H2 tagging variants with risk of late-onset Parkinson’s disease in independent cohorts of N=786 unrelated, clinically diagnosed PD patients and N=751 unrelated, healthy controls. Non-H1/H2 tagging variants had an r2 < 1.00 linkage disequilibrium score relative to MAPT H1/H2-defining SNP rs8070723. Base positions are aligned to Homo sapiens chromosome build GRCh38. For common variants (MAF≥1%), ORs, 95% CIs, and p-values result from logistic regression models that were adjusted for age and sex. ORs correspond to presence of the minor allele. For rare variants (MAF<1%), the proportion of subjects with a copy of the minor allele was compared between PD patients and controls using Fisher’s exact test.
| Gene | Base Position | rsID | AA | Minor allele | MAF (cases) | MAF (controls) | OR (95% CI) | P value | CADD * |
|---|---|---|---|---|---|---|---|---|---|
| CRHR1 | 45829607 | rs75638861 | V161M | A | 1.50% | 1.60% | 0.92 (0.51, 1.68) | 0.79 | 10.5 |
| SPPL2C | 45845108 | rs117261590 | P68S | T | 0.36% | 0.21% | - | 0.52 | 0 |
| SPPL2C | 45845274 | rs17763658 | R123Q | A | 7.39% | 6.96% | 1.02 (0.76, 1.37) | 0.9 | 7.33 |
| SPPL2C | 45845405 | rs142955406 | G167W | T | 0.12% | 0.14% | - | 1 | 21.8 |
| SPPL2C | 45845531 | rs929223 | E209K | A | 2.27% | 3.04% | 0.84 (0.50, 1.39) | 0.49 | 11.98 |
| SPPL2C | 45845814 | rs242944 | R303H | G | 41.30% | 46.76% | 0.80 (0.64, 0.99) | 0.045 | 0 |
| SPPL2C | 45845826 | rs148362814 | R307Q | A | 0.65% | 0.21% | - | 0.1 | 0.01 |
| MAPT | 45942346 | rs242557 | -- | A | 39.92% | 35.07% | 1.15 (0.93, 1.41) | 0.19 | 0 |
| MAPT | 46003698 | rs8070723 | -- | G | 17.84% | 25.79% | 0.57 (0.46, 0.70) | <0.001 | 0 |
| KANSL1 | 46171833 | rs17585974 | K104T | G | 15.17% | 20.60% | 0.61 (0.49, 0.76) | <0.001 | 24.7 |
| KANSL1 | 46171573 | rs149566146 | G191C | A | 0.18% | 0.00% | - | 0.25 | 22.9 |
| KANSL1 | 46171524 | rs144882998 | N207S | C | 0.06% | 0.07% | - | 1 | 10.7 |
| KANSL1 | 46171509 | rs141110759 | H212R | C | 0.06% | 0.00% | - | 1 | 1.15 |
| KANSL1 | 46171482 | rs17662853 | T221I | T | 15.24% | 14.62% | 1.04 (0.83, 1.31) | 0.72 | 23.2 |
| KANSL1 | 46171471 | rs35643216 | N225D | C | 15.25% | 20.43% | 0.62 (0.50, 0.77) | <0.001 | 10.71 |
| KANSL1 | 46032108 | rs7220988 | P1010L | T | 44.76% | 40.06% | 1.30 (1.05, 1.61) | 0.018 | 18.02 |
| KANSL1 | 46031624 | rs201083879 | Q1057R | C | 0.12% | 0.00% | - | 0.5 | 21.6 |
| NSF | 46626698 | rs748314870 | F63S fs 77Stop | T/- | 1.85% | 2.12% | 0.82 (0.39, 1.74) | 0.61 | 27.6 |
| NSF | 46694579 | rs373218599 | V431M | A | 0.06% | 0.00% | - | 1 | 14.89 |
| NSF | 46704811 | rs757532604 | T476M | T | 22.13% | 20.87% | 1.06 (0.87, 1.31) | 0.55 | 24.7 |
AA= Amino Acid. MAF= Minor Allele Frequency. OR=odds ratio. CI=confidence interval. CADD= Combined Annotation Dependent Depletion.
A CADD greater than 20 indicates a variant that is in the top 1% of deleterious variants.