TABLE 2.
Analysis of LSD subgroups associated gene rare variant burden in PD (MAF < 0.01).
| WES cohort | WGS cohort | |||||||
|
|
||||||||
| Variants group | (1) Missense | (2) Dmis | (3) LoF | (4) LoF + Dmis | (1) Missense | (2) Dmis | (3) LoF | (4) LoF + Dmis |
| Sphingolipidoses | 339 (1.35E-13) | 143 (3.50E-13) | 51 (0.00073) | 194 (8.72E-16) | 261 (0.00046) | 113 (0.058) | 15 (0.015) | 128 (0.008) |
| Sphingolipidoses (exclude GBA) | 283 (0.025) | 99 (0.127) | 30 (0.705) | 129 (0.116) | 225 (0.088) | 86 (0.849) | 10 (0.068) | 96 (0.454) |
| Mucopolysaccharidoses | 295 (0.445) | 101 (0.163) | 27 (0.777) | 128 (0.181) | 213 (0.002) | 78 (0.098) | 9 (0.675) | 87 (0.086) |
| Glycogen storage disease | 61 (0.270) | 28 (0.080) | 6 (0.701) | 34 (0.084) | 146 (0.410) | 52 (0.309) | 4 (0.138) | 56 (0.280) |
| Glycoproteinoses | 179 (0.266) | 76 (0.880) | 14 (0.220) | 90 (0.866) | 61 (0.386) | 23 (0.102) | 3 (0.388) | 26 (0.113) |
| Lipid storage diseases | 15 (0.787) | 3 (0.755) | – | 3 (0.755) | 15 (0.399) | 2 (0.742) | – | 2 (0.742) |
| Post-translational modification defects | 92 (0.170) | 42 (0.102) | 18 (0.630) | 60 (0.103) | 79 (0.031) | 36 (0.604) | 6 (0.567) | 42 (0.607) |
| Integral membrane protein disorders | 162 (0.149) | 52 (0.107) | 7 (0.409) | 59 (0.084) | 121 (0.169) | 48 (0.286) | 3 (0.446) | 51 (0.282) |
| Neuronal ceroid lipofuscinoses | 287 (0.265) | 82 (0.595) | 19 (0.906) | 101 (0.664) | 239 (0.600) | 62 (0.235) | 6 (0.663) | 68 (0.219) |
| Lysosome-related organelles disorders | 581 (0.160) | 129 (0.229) | 33 (0.647) | 162 (0.420) | 461 (0.253) | 86 (0.859) | 13 (0.428) | 99 (0.840) |
| Pycnodysostosis | 3 (1.000) | 1 (0.521) | – | 1 (0.521) | 6 (0.218) | 2 (0.077) | 1 (0.297) | 3 (0.086) |
| Sialuria | 21 (0.700) | 10 (0.681) | 2 (0.690) | 12 (0.878) | 16 (0.651) | 10 (0.575) | 1 (0.377) | 11 (0.440) |
Data were shown as number of variants (SKAT-O P-value).
MAF, minor allele frequency; LoF, loss of function; Dmis, damaging missense (ReVe > 0.7). The estimated number of independent tests was 6 in the analysis of LSD gene sets, corresponding to a Bonferroni-corrected significance threshold of P < 0.0083. We considered those results with a P-value < 0.05, but not surviving the Bonferroni correction, as “suggestive”.
Bold text indicates a statistically significant assciation with a p-value < 0.05.