Table 4.
Gene burden analysis 2.
| Gene | Number variants | Percentage variants retained | Odds ratio ExACa | P value | P correctedb | Odds ratio ExAC NFEa | P value | P correctedb | Odds ratio CSVSa | P value | P correctedb |
|---|---|---|---|---|---|---|---|---|---|---|---|
| GJB2 | 6 | 80 | 0.5 (0.27–0.93) | 2.91E-02 | 1.75E-01 | 3.2 (2.12–4.83) | 2.75E-08 | 1.65E-07 | 2.06 (1.33–3.19) | 1.14E-03 | 6.85E-03 |
| SEMA3D | 2 | 50 | 1.1 (0.76–1.61) | 6.13E-01 | 1 | 0.8 (0.53–1.21) | 2.85E-01 | 5.70E-01 | 2.67 (1.94–3.68) | 2.03E-09 | 4.06E-09 |
| CLDN14 | 2 | 50 | 4.47 (2.55–7.83) | 1.67E-07 | 3.35E-07 | 23.18 (13.81–38.9) | <1.00E-15 | <1.00E-15 | 4.64 (2.65–8.11) | 7.47E-08 | 1.49E-07 |
| SLC26A4 | 6 | 40 | 1.18 (0.72–1.93) | 5.04E-01 | 1 | 2.88 (1.89–4.38) | 8.13E-07 | 4.88E-06 | 2.33 (1.51–3.59) | 1.23E-04 | 7.37E-04 |
| NFKB1 | 3 | 30 | 1.37 (0.99–1.91) | 5.92E-02 | 1.78E-01 | 1.43 (1.03–1.98) | 3.37E-02 | 1.01E-01 | 2.73 (2.03–3.66) | 2.21E-11 | 6.62E-11 |
| POU4F3 | 1 | 25 | 1.56 (1.47–1.66) | < 1.00E-15 | < 1.00E-15 | 1.06 (1–1.14) | 6.16E-02 | 6.16E-02 | 1.84 (1.73–1.95) | <1.00E-15 | <1.00E-15 |
| ESRRB | 3 | 21 | 4.41 (3.31–5.89) | < 1.00E-15 | < 1.00E-15 | 3.39 (2.52–4.55) | <1.00E-15 | <1.00E-15 | 1.84 (1.33–2.54) | 2.04E-04 | 6.12E-04 |
| USH1G | 5 | 21 | 2.51 (1.38–4.56) | 2.66E-03 | 1.33E-02 | 20.27 (12.06–34.06) | <1.00E-15 | <1.00E-15 | 4.67 (2.68–8.17) | 6.11E-08 | 3.05E-07 |
| CCDC50 | 1 | 20 | 0.54 (0.44–0.66) | 7.23E-10 | 7.23E-10 | 0.7 (0.59–0.84) | 1.41E-04 | 1.41E-04 | 1.38 (1.19–1.61) | 3.38E-05 | 3.38E-05 |
| P2RX2 | 3 | 14 | 2.57 (1.93–3.42) | 8.71E-11 | 2.61E-10 | 3.14 (2.38–4.14) | < 1.00E-15 | < 1.00E-15 | 2.67 (2.01–3.55) | 1.12E-11 | 3.36E-11 |
| FAM136A | 1 | 13 | 140.36 (131.25–150.11) | < 1.00E-15 | < 1.00E-15 | 76.75 (71.75–82.09) | < 1.00E-15 | < 1.00E-15 | 3.68 (3.41–3.97) | < 1.00E-15 | < 1.00E-15 |
| RDX | 2 | 12 | 4.49 (3.59–5.61) | < 1.00E-15 | < 1.00E-15 | 2.69 (2.12–3.4) | < 1.00E-15 | < 1.00E-15 | 3.33 (2.65–4.2) | < 1.00E-15 | < 1.00E-15 |
| TPRN | 3 | 12 | 2.24 (1.7–2.96) | 1.46E-08 | 4.37E-08 | 6.55 (5.1–8.4) | < 1.00E-15 | < 1.00E-15 | 2.95 (2.26–3.86) | < 1.00E-15 | < 1.00E-15 |
| ESPN | 2 | 11 | 10.69 (9–12.69) | 0.00E+00 | < 1.00E-15 | 10.26 (8.64–12.19) | < 1.00E-15 | < 1.00E-15 | 2.01 (1.64–2.46) | 9.24E-12 | 1.85E-11 |
| SLC12A2 | 1 | 8 | 281.71 (246.32–322.17) | < 1.00E-15 | < 1.00E-15 | 308.08 (269.39–352.33) | < 1.00E-15 | < 1.00E-15 | 14.77 (12.86–16.96) | < 1.00E-15 | < 1.00E-15 |
| PRKCB | 1 | 8 | 15.1 (13.03–17.48) | < 1.00E-15 | < 1.00E-15 | 10.5 (9.05–12.19) | < 1.00E-15 | < 1.00E-15 | 5.54 (4.75–6.46) | < 1.00E-15 | < 1.00E-15 |
| MYH14 | 3 | 6 | 14.44 (10.42–20.03) | < 1.00E-15 | < 1.00E-15 | 28.12 (20.38–38.79) | < 1.00E-15 | < 1.00E-15 | 5.86 (4.16–8.25) | < 1.00E-15 | < 1.00E-15 |
| ADD1 | 1 | 3 | 563.42 (492.71–644.27) | < 1.00E-15 | < 1.00E-15 | 308.08 (269.39–352.33) | < 1.00E-15 | < 1.00E-15 | 14.77 (12.86–16.96) | < 1.00E-15 | < 1.00E-15 |
a
Odds ratios were calculated in the 95% confidence interval.
b
P-values were corrected with Bonferroni method.
List of 18 genes showing a significant excess of previously reported missense exonic variants in patients with sporadic MD, according to the MAF observed in CSVS Spanish database (N = 1579), compared with global ExAC population (N = 60,706) and non-Finnish European ExAC population (N = 33,370). In bold, selected genes with higher percentage of variants retained (>20%) and significant OR on Spanish and NFE populations. Selected SNV can be consulted in Table S5.