Table 1.
List of synaptic genes showing enrichment of missense variants in Spanish patients with Meniere disease and tinnitus extreme phenotype (MD-EP). Three reference datasets (Non-Finnish European from gnomAD.v2 or gnomAD.v3, Spanish from CSVS) were used to compare allelic frequencies for each gene in the MD cohort. Listed genes were significant when they were compared against CSVS reference dataset.
| Gene | #variants | [gnomAD.v2] OR(CI) | EF | Corrected p | [gnomAD.v3] OR(CI) | EF | Corrected p | [CSVS] OR(CI) | EF | Corrected p |
|---|---|---|---|---|---|---|---|---|---|---|
| PRUNE2 | 9 | 6.02(3.60–10.07) | 0.83 | 1.44E-08 | 5.89(3.52-9.85) | 0.83 | 2.75E-08 | 5.40(3.17-9.20) | 0.81 | 1.08E-06 |
| AKAP9 | 6 | 12.32(5.48–27.68) | 0.92 | 2.2E-06 | 13.89(6.17-31.27) | 0.93 | 4.04E-07 | 6.68(2.86-15.57) | 0.85 | 2.07E-02 |
| SORBS1 | 6 | 10.93(4.87–24.55) | 0.91 | 1.31E-05 | 11.52(5.12-25.93) | 0.91 | 6.57E-06 | 7.73(3.30-18.12) | 0.87 | 4.86E-03 |
| ITGAX | 5 | 73.02(29.68–179.66) | 0.99 | <1.00E-15 | 61.68(24.88-152.94) | 0.98 | <1.00E-15 | 14.29(5.40-37.86) | 0.93 | 1.63E-04 |
| ANK2 | 4 | 18.30(6.78–49.40) | 0.95 | 1.80E-05 | 19.95(7.36-54.08) | 0.95 | 7.55E-06 | 21.93(7.02-68.48) | 0.95 | 2.02E-04 |
| KIF20B | 4 | 7.76(3.45–17.49) | 0.87 | 1.42E-03 | 8.43(3.74-19.01) | 0.88 | 5.27E-04 | 16.57(6.71-40.92) | 0.94 | 2.15E-06 |
| TSC2 | 4 | 63.73(23.35–173.96) | 0.98 | 8.38E-13 | 53.56(19.47-147.30) | 0.98 | 2.35E-11 | 21.93(7.02-68.48) | 0.95 | 2.02E-04 |
| SPHK2 | 4 | 5.47(2.25–13.28) | 0.82 | NS | 5.51(2.27-13.39) | 0.82 | NS | 8.45(3.30-21.64) | 0.88 | 1.61E-02 |
| SYNPO | 4 | 74.87(27.35-204.94) | 0.99 | <1.00E-15 | 78.43(28.21-218.03) | 0.99 | <1.00E-15 | 32.90(9.84-110.01) | 0.97 | 2.66E-05 |
| LRPPRC | 4 | 49.75(18.29–135.32) | 0.98 | 3.73E-11 | 73.20(26.39-203.03) | 0.99 | 4.19E-13 | 21.93(7.02-68.48) | 0.95 | 2.02E-04 |
| XYLT1 | 4 | 2.00(0.74–5.38) | 0.50 | NS | 2.09(0.78-5.61) | 0.52 | NS | 10.95(3.77-31.82) | 0.91 | 2.04E-02 |
| ALCAM | 3 | 8.22(2.62–25.81) | 0.88 | NS | 9.48(3.01-29.81) | 0.89 | NS | 24.67(6.49-93.76) | 0.96 | 4.77E-03 |
| CDH13 | 3 | 12.15(4.50–32.85) | 0.92 | 1.60E-03 | 13.09(4.83-35.46) | 0.92 | 8.05E-04 | 33.08(9.87-110.87) | 0.97 | 2.69E-05 |
| DOCK7 | 3 | 52.57(16.54–167.10) | 0.98 | 3.53E-08 | 70.09(21.61-227.27) | 0.99 | 2.71E-09 | 24.67(6.49-93.76) | 0.96 | 4.77E-03 |
| BIN1 | 3 | 56.70(17.82–180.42) | 0.98 | 1.53E-08 | 73.20(22.54-237.74) | 0.99 | 1.72E-09 | 49.36(10.97-222.15) | 0.98 | 7.11E-04 |
| FLII | 3 | 26.77(8.48–84.44) | 0.96 | 3.87E-05 | 33.95(10.66-108.12) | 0.97 | 4.64E-06 | 24.67(6.49-93.76) | 0.96 | 4.77E-03 |
| HSPA4L | 3 | 17.41(5.53–54.77) | 0.94 | 1.95E-03 | 16.71(5.29-52.75) | 0.94 | 2.98E-03 | 16.44(4.60-58.77) | 0.94 | 3.11E-02 |
| IQSEC1 | 3 | 32.85(10.39–103.82) | 0.97 | 5.12E-06 | 30.49(9.59-96.94) | 0.97 | 1.32E-05 | 24.67(6.49-93.76) | 0.96 | 4.77E-03 |
| IQSEC3 | 3 | 4.16(1.33–13.04) | 0.76 | NS | 4.47(1.43-14.03) | 0.78 | NS | 16.44(4.60-58.77) | 0.94 | 3.11E-02 |
| LLGL1 | 3 | 27.29(10.06–74.03) | 0.96 | 1.57E-07 | 25.08(9.21-68.31) | 0.96 | 5.53E-07 | 13.92(4.69-41.32) | 0.93 | 4.01E-03 |
| MADD | 3 | 128.54(39.58-417.46) | 0.99 | 1.26E-12 | 73.20(22.54-237.74) | 0.99 | 1.72E-09 | 49.36(10.97-222.15) | 0.98 | 7.11E-04 |
| MBP | 3 | 170.13(51.78–559.02) | 0.99 | <1.00E-15 | 82.35(25.24-268.68) | 0.99 | 4.99E-10 | 16.44(4.60-58.77) | 0.94 | 3.11E-02 |
| MPRIP | 3 | 82.62(25.77–264.88) | 0.99 | 2.10E-10 | 78.43(24.09-255.39) | 0.99 | 8.32E-10 | 49.36(10.97-222.15) | 0.98 | 7.11E-04 |
| NRCAM | 3 | 69.68(21.82-222.56) | 0.99 | 1.49E-09 | 50.67(15.78-162.74) | 0.98 | 8.07E-08 | 49.36(10.97-222.15) | 0.98 | 7.11E-04 |
| TRAP1 | 3 | 13.72(4.37–43.13) | 0.93 | 1.39E-02 | 11.27(3.58-35.47) | 0.91 | NS | 24.67(6.49-93.76) | 0.96 | 4.77E-03 |
| VCAN | 3 | 90.37(28.13–290.35) | 0.99 | 7.41E-11 | 76.61(23.55-249.22) | 0.99 | 1.07E-09 | 24.67(6.49-93.76) | 0.96 | 4.77E-03 |
| MYO18A | 3 | 204.11(72.08–577.95) | 0.99 | <1.00E-15 | 169.90(58.69-491.88) | 0.99 | <1.00E-15 | 33.08(9.87-110.87) | 0.97 | 2.69E-05 |
| MYO5A | 3 | 13.72(4.37–43.13) | 0.93 | 1.39E-02 | 16.97(5.37-53.37) | 0.94 | 2.62E-03 | 16.44(4.60-58.77) | 0.94 | 3.11E-02 |
| PPP1R9A | 2 | 171.57(51.97–566.41) | 0.99 | <1.00E-15 | 127.78(38.15-427.99) | 0.99 | 7.12E-12 | 24.87(6.52–94.93) | 0.96 | 4.84E-03 |
| CCDC22 | 2 | 7.38(2.72–20.04) | 0.86 | NS | 8.37(3.08–22.75) | 0.88 | NS | 14.06(4.71–41.98) | 0.93 | 4.08E-03 |
| EPX | 2 | 8.17(3.01–22.19) | 0.88 | NS | 8.69(3.20–23.64) | 0.88 | 4.28E-02 | 11.61(3.95–34.11) | 0.91 | 1.54E-02 |
OR (CI)= odds ratio (95% confidence interval), EF=etiological fraction, p-corrected values obtained after Bonferroni correction, genes are ordered by number of variants, NS=Nonsignificant p-corrected values