Table 2.
Frequency of GBA variants by Parkinson’s disease status
| Variant | Severitya | PD patients (n=735), % (n) |
Controls (n=662), % (n) |
Odds Ratio (95% CI) |
p-value | IBD Exomes Portal Controls, % |
|---|---|---|---|---|---|---|
| Heterozygous carriers | ||||||
| GBA | ||||||
| c.84dupGb | severe | 1.5 (11) | 0.15 (1) | 10.1 (1.3-78.1) | <0.01 | 0.05 |
| p.R44C | unknown | 0.27 (2) | 1.06 (7) | 0.3 (0.1-1.2) | 0.07 | 0.18 |
| p.N188S | severe | 0.14 (1) | 0 (0) | NA | NA | 0 |
| p.E326K | benignc | 1.63 (12) | 0.3 (2) | 5.5 (1.2-24.6) | 0.01 | 0.9 |
| p.T369M | benignc | 0 (0) | 0 (0) | NA | NA | 0.6 |
| p.N370Sb | mild | 11.84 (87) | 5.58 (37) | 2.3 (1.5-3.4) | <0.0001 | 5.9 |
| p.A384D | unknown | 0.14 (1) | 0 (0) | NA | NA | 0 |
| p.V394Lb | severe | 0.14 (1) | 0 (0) | NA | NA | 0.05 |
| p.T410M | unknown | 0 (0) | 0.15 (1) | NA | NA | 0 |
| p.L444Pb | severe | 0.27 (2) | 0 (0) | NA | NA | NC |
| p.L461P | unknown | 0.14 (1) | 0 (0) | NA | NA | 0 |
| p.R496Hb | mild | 0.95 (7) | 0.3 (2) | 3.2 (0.7-15.4) | 0.1 | NC |
|
| ||||||
| Total mild GBA variant carriers | 12.93 (95) | 5.88 (39) | 2.4 (1.6-3.5) | <0.0001 | ||
| Total severe GBA variant carriers | 1.9 (14) | 0.15 (1) | 12.9 (1.7-98) | 0.001 | ||
| Total heterozygous GBA variant carriers | 17.01 (125) | 7.54 (50) | 2.5 (1.8-3.6) | <0.0001 | ||
|
| ||||||
| Homozygous/compound heterozygous | ||||||
| p.N370S/p.R496H | 0.27 (2) | 0 (0) | NA | NA | ||
| p.E326K/p.N370S | 0.14 (1) | 0 (0) | NA | NA | ||
| p.T369M/84GG | 0.27 (2) | 0 (0) | NA | NA | ||
| p.N370S/p.N370S | 0.14 (1) | 0 (0) | NA | NA | ||
| p.N370S/p.L444P | 0.14 (1) | 0 (0) | NA | NA | ||
|
| ||||||
| Total homozygous and compound heterozygous | 0.95 (7) | 0 (0) | NA | NA | ||
|
| ||||||
| Total heterozygous, homozygous, and compound heterozygous carriers | 17.96 (132) | 7.54 (50) | 2.7 (1.9-3.8) | <0.0001 | ||
PD, Parkinson’s disease; n, number; CI, confidence interval; IBD, inflammatory Bowel disease; NA, not applicable (OR and p values cannot be calculated if there is a value of 0 in one of the groups); NC, not called (due to the homology with pseudo-GBA, some variants cannot be called properly)
The severity was determined by the effect of the variant in Gaucher’s disease. Variants that in homozygous form cause the mild type I of Gaucher’s disease are considered as “mild”, and those that cause the severe forms of Gaucher’s disease are considered as “severe”.
Included in 7-variant genotyping panel.
These variants do not cause Gaucher’s disease, therefore defined as benign. However, they may still be risk factors for PD.