Table 2

Burden analysis of rare variants (MAF <0.0001) in ALS-associated genes among 1587 patients with ALS and 1866 inhouse controls

GenesRare variants*P valueDamaging*P valueNon-damaging*P value
Causative genes
SOD1 44, 2<1.0E-743, 1<1.0E-71, 10.51
FUS 32, 13<1.0E-719, 3<1.0E-613, 100.286
VAPB 5, 60.991, 04, 60.52
TARDBP 19, 2<1.0E-715, 2<1.0E-74, 0<1.0E-7
OPTN 11, 80.3186, 0<1.0E-75, 80.76
VCP 5, 20.1144, 10.0761, 10.51
UBQLN2 7, 60.4425, 0<1.0E-72, 40.414
PFN1 2, 20.8261, 10.511, 10.51
HNRNPA1 2, 10.2881, 01, 10.51
CHCHD10 4, 40.9662, 10.2882, 30.702
TBK1 13, 70.0610, 30.0083, 40.850
NEK1 34, 270.11217, 60.00216, 200.732
ANXA11 15, 200.7367, 30.2025, 140.082
KIF5A 7, 80.8023, 20.5684, 60.52
DNAJC7 9, 60.2823, 10.1466, 40.454
Risk or susceptive genes
ALS2 25, 350.40815, 190.83410, 160.512
SETX 41, 390.34821, 170.17820, 220.098
ANG 2, 70.1041, 30.3421, 40.178
FIG4 17, 90.0269, 50.0888, 40.16
SIGMAR1 3, 10.1461, 02, 10.288
CHMP2B 4, 20.3764, 10.0760, 1
SQSTM1 10, 80.3606, 40.4544, 40.966
DAO 9, 120.6428, 50.2421, 70.024
DCTN1 7, 210.0222, 90.0325, 120.194
MATR3 4, 80.2562, 30.7022, 50.36
TUBA4A 2, 50.361, 50.091, 0
CCNF 20, 120.0629, 50.08811, 70.188
TIA1 5, 60.9901, 20.6544, 40.966
GLT8D1 7, 40.2983, 20.5684, 20.376
CYLD 5, 70.7961, 40.1784, 30.528
SPG11 2, 35<1.0E-72, 16<1.0E-70, 19<1.0E-7
NEFH 19, 280.36212, 200.28811, 80.318
PRPH 9, 60.2828, 30.071, 30.342
PNPLA6 10, 160.5123, 40.857, 120.330
ELP3 7, 110.4465, 50.7822, 60.140
EWSR1 8, 40.163, 30.7625, 10.048
ERBB4 9, 120.6425, 60.994, 60.52
MAPT 3, 110.0982, 30.7021, 80.010
GRN 17, 120.1187, 30.20210, 90.544
  • The p values displayed are from the sequencing kernel association test.

  • *Represent the number of rare variants, damaging variants and non-damaging variants in 1587 patients with ALS and 1866 inhouse controls. Damaging variants were defined as P/LP variants in the group I genes according to the American College of Medical Genetics and as deleterious variants in the group II genes, all of which are shown in online supplemental table S14 and online supplemental table S15.

  • ALS, amyotrophic lateral sclerosis; MAF, minor allele frequency; P/LP, pathogenic/likely pathogenic.