Table 2.
Discovery and Replication Cohorts Used to Examine Burden of Spastic Paraplegia Mutations
| Discovery Cohort | Replication Cohort 1 | Replication Cohort 2 | Replication Cohort 3 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Platform | MS Replication Chip | MS Replication Chip | MS Replication Chip | MS Replication Chip | ||||||||||||
| Variants | 331,536 | 169a | 169a | 169a | ||||||||||||
| Cohort | UCSF | NARCOMSb | Australia | Italy | ||||||||||||
| Diagnosisd | CTL | RMS | SPMS | PPMS | CTL | RMS | SPMS | PPMS | CTL | RMS | SPMS | PPMS | CTL | RMS | SPMS | PPMS |
| Samples | 100 | 930 | 203 | 48c | 321 | 586 | 222 | 122 | 410 | 452 | 75 | 57c | 156 | 280 | 87 | 87 |
| Age at onset | ||||||||||||||||
| Mean ± SD | NA | 32.8 ± 9.4 | 31.3 ± 9.3 | 42.3 ± 11.2 | NA | 32.6 ± 9.8 | 31.0 ± 9.2 | 40.7 ± 11.1 | NA | 36 ± 9.8 | 35 ± 9.4 | 42 ± 10.8 | NA | 28.2 ± 8.9 | 29.1 ± 9.4 | 39.9 ± 10.1 |
| Median, range | NA | 32 (5–64) | 31 (11–58) | 42 (22–66) | NA | 33 (4–61) | 30 (10–65) | 41 (12–66) | NA | 36 (14–64) | 33 (15–59) | 41 (20–72) | NA | 27 (7–52) | 27 (15–59) | 40 (19–60) |
| Disease duration | ||||||||||||||||
| Mean ± SD | NA | 12.6 ± 9.5 | 23.0 ± 10.0 | 11.2 ± 7.4 | NA | 21.9 ± 11.3 | 28 ± 10.9 | 22.6 ± 10.4 | NA | 8 ± 6.5 | 21 ± 10.2 | 13 ± 9.9 | NA | 8.1 ± 7.0 | 17.3 ± 7.9 | 10.8 ± 8.2 |
| Median range | NA | 12 (0–54) | 22 (3–48) | 10 (0–37) | NA | 20 (1–66) | 28 (0–58) | 20 (2–56) | NA | 6 (0–41) | 22 (3–44) | 10 (1–43) | NA | 6 (0–37) | 17 (3–41) | 9 (1–45) |
| Female sex | 22% | 74% | 68% | 40% | 47% | 81% | 81% | 61% | 77% | 77% | 76% | 61% | 38% | 66% | 70% | 57% |
a
One hundred sixty‐nine HSP‐related variants were examined in these replication cohorts.
b
North American Research Committee on Multiple Sclerosis.
c
Patients met 2010 International Panel Criteria for PPMS.
d
CTL = control subjects; RMS = relapsing MS patients excluding those with known secondary progression; SPMS = secondary progressive MS; PPMS = primary progressive MS.
SD = standard deviation; UCSF = University of California San Francisco; NA = not applicable; HSP = hereditary spastic paraplegia.