Table 2.
Genes with pathogenic or likely pathogenic variants in cases and/or controls
| GnomAD | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Gene | Case (%) | Control (%) | P-value | Adj. P-value | Est. OR | 95% CI | GnomAD (%) | P-value | Adj. P-value | Est. OR | 95% CI |
| NEK1 | 54 (0.90) | 1 (0.04) | 2.57 × 10−7 | 1.03 × 10−5 | 21.84 | 3.75–875.45 | 52 (0.04) | 9.19 × 10−31 | 3.58 × 10−29 | 11.84 | 7.93–17.68 |
| SOD1 | 38 (0.63) | 2 (0.08) | 3.15 × 10−4 | 1.23 × 10−2 | 7.66 | 1.98–65.66 | 8 (0.01) | 4.47 × 10−34 | 1.79 × 10−32 | 54.09 | 24.83–133.75 |
| FUS | 16 (0.27) | 0 (0.00) | 9.40 × 10−3 | 0.36 | ∼6.43 | 1.55–Inf | 5 (0.00) | 5.01 × 10−14 | 1.85 × 10−12 | 36.19 | 12.67–126.77 |
| OPTN | 24 (0.40) | 2 (0.08) | 1.58 × 10−2 | 0.58 | 4.83 | 1.2–42.2 | 20 (0.01) | 2.29 × 10−15 | 8.72 × 10−14 | 13.62 | 7.2–26.01 |
| TARDBP | 13 (0.22) | 0 (0.00) | 2.59 × 10−2 | 0.93 | ∼5.22 | 1.22–Inf | 6 (0.00) | 1.12 × 10−10 | 3.92 × 10−9 | 24.57 | 8.71–79.01 |
| NEFH | 6 (0.10) | 8 (0.33) | 3.26 × 10−2 | 1.00 | 0.30 | 0.09–0.99 | 32 (0.02) | 0.23 | 1.00 | 1.73 | 0.53–4.48 |
| PRPH | 9 (0.15) | 0 (0.00) | 6.79 × 10−2 | 1.00 | ∼3.61 | 0.79–Inf | 29 (0.02) | 2.85 × 10−3 | 7.40 × 10−2 | 3.51 | 1.46–7.63 |
| TBK1 | 16 (0.27) | 2 (0.08) | 0.12 | 1.00 | 3.21 | 0.75–28.84 | 3 (0.00) | 2.88 × 10−13 | 1.04 × 10−11 | 52.92 | 14.76–285.4 |
| ITPR2 | 12 (0.20) | 1 (0.04) | 0.13 | 1.00 | 4.82 | 0.71–205.93 | 47 (0.03) | 2.48 × 10−3 | 6.70 × 10−2 | 2.89 | 1.4–5.54 |
| SPG11 | 32 (0.53) | 7 (0.29) | 0.16 | 1.00 | 1.84 | 0.8–4.94 | 126 (0.09) | 1.28 × 10−6 | 4.35 × 10−5 | 2.88 | 1.89–4.28 |
| C19orf12 | 0 (0.00) | 1 (0.04) | 0.29 | 1.00 | 0.00 | 0–15.64 | 13 (0.01) | 0.62 | 1.00 | 0.00 | 0–3.68 |
| SQSTM1 | 0 (0.00) | 1 (0.04) | 0.29 | 1.00 | 0.00 | 0–15.64 | 10 (0.01) | 1.00 | 1.00 | 0.00 | 0–5.05 |
| CHRNA4 | 2 (0.03) | 2 (0.08) | 0.32 | 1.00 | 0.40 | 0.03–5.53 | 9 (0.01) | 0.23 | 1.00 | 2.48 | 0.26–11.99 |
| VCP | 5 (0.08) | 0 (0.00) | 0.33 | 1.00 | ∼2.01 | 0.37–Inf | 4 (0.00) | 3.36 × 10−4 | 1.04 × 10−2 | 14.15 | 3.05–71.34 |
| ALS2 | 7 (0.12) | 5 (0.21) | 0.34 | 1.00 | 0.56 | 0.15–2.24 | 32 (0.02) | 3.57 × 10−2 | 0.81 | 2.48 | 0.92–5.71 |
| SYNE1 | 18 (0.30) | 10 (0.41) | 0.41 | 1.00 | 0.72 | 0.32–1.75 | 116 (0.09) | 3.72 × 10−2 | 0.81 | 1.76 | 1.01–2.9 |
| CACNA1H | 29 (0.48) | 15 (0.62) | 0.41 | 1.00 | 0.77 | 0.4–1.56 | 27 (0.02) | 1.91 × 10−3 | 5.55 × 10−2 | 3.77 | 1.56–8.27 |
| LRP10 | 1 (0.02) | 1 (0.04) | 0.49 | 1.00 | 0.40 | 0.01–31.48 | 13 (0.01) | 1.00 | 1.00 | 0.87 | 0.02–5.8 |
| TAF15 | 1 (0.02) | 1 (0.04) | 0.49 | 1.00 | 0.40 | 0.01–31.48 | 11 (0.01) | 1.00 | 1.00 | 1.02 | 0.02–7 |
| CHRNA3 | 9 (0.15) | 5 (0.21) | 0.56 | 1.00 | 0.72 | 0.22–2.74 | 58 (0.04) | 0.12 | 1.00 | 1.76 | 0.76–3.57 |
List of the first 20 of 40 genes in which pathogenic or likely pathogenic variants were found in cases and/or controls (sorted on increasing P-value). On the left, the absolute number of ALS patients and controls of our cohort with minimal one pathogenic or likely pathogenic variant in that gene is indicated along with the proportion of total cases (n = 6013) and controls (n = 2411) as a percentage in brackets. P-value, adjusted (Adj.) P-value after correction for multiple testing, estimated odds ratio and 95% confidence interval are shown in separate columns. To the right, a comparison with controls of the gnomAD database. Repeat expansions and SNP rs12608932 in UNC13A are not included in this table. The full table with all 40 genes can be found in the Supplementary material (Supplementary Table 5). Adj = adjusted; CI = confidence interval; Est = estimated; Inf = infinity; NMHP = neuromuscular homepage; OR = odds ratio.