Table 1.
GWAS results in genome-wide suggestive loci in the PCL discovery cohort, Canadian first replication cohort, PCL second replication cohort, and combined analyses.
| SNP | Chr | Position | Ref/Eff | Nearest gene | Dist (kb) | PCL discovery cohort (D) N = 390a | Canadian first replication cohort (R1) N = 192b | Combined analysis 1 (D & R1) | PCL second replication cohort (R2) N = 188c | Combined analysis 2 (D, R1 & R2) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EAF | OR (95% CI) | P | EAF | OR (95% CI) | P | OR (95% CI) | P | I2 | EAF | OR (95% CI) | P | OR (95% CI) | P | I2 | ||||||
| rs10928931 | 2 | 130522107 | G/C | AC079776.1 | 104.7 | 0.92 | 5.16 (2.5–10.5) | 5.67E–06 | NAd | NAd | NAd | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| rs62178885 | 2 | 133645476 | G/A | NCKAP5 | 0.0 | 0.36 | 2.10 (1.5–2.9) | 7.05E–06 | 0.33 | 1.06 (0.6–1.8) | 0.81 | 1.72 (1.3–2.3) | 9.67E−05 | 80.2 | NA | NA | NA | NA | NA | NA |
| rs75426794 | 6 | 28274651 | A/G | PGBD1 | 4.3 | 0.17 | 2.55 (1.7–3.8) | 4.26E−06 | 0.20 | 0.85 (0.5–1.6) | 0.61 | 1.84 (1.3–2.6) | 3.38E−04 | 88.3 | NA | NA | NA | NA | NA | NA |
| rs9498000 | 6 | 148645188 | G/A | SASH1 | 0.0 | 0.07 | 3.80 (2.1–6.8) | 7.45E−06 | 0.06 | 0.69 (0.3–1.8) | 0.44 | 2.40 (1.5–4.0) | 5.79E−04 | 88.6 | NA | NA | NA | NA | NA | NA |
| rs893507 | 10 | 133013187 | T/C | TCERG1L | 0.0 | 0.15 | 2.66 (1.7–4.1) | 9.03E−06 | 0.09 | 3.37 (1.3–8.9) | 0.01 | 2.77 (1.9–4.1) | 4.45E−07 | 0.0 | 0.11 | 5.45 (2.3–12.8) | 1.02E−04 | 3.11 (2.2–4.5) | 5.31E−10 | 8.1 |
| rs61945410 | 12 | 125980301 | C/T | TMEM132B | 0.0 | 0.27 | 0.40 (0.3–0.6) | 9.67E−06 | 0.22 | 2.27 (1.2–4.2) | 0.01 | 0.68 (0.5–1.0) | 2.73E−02 | 95.4 | NA | NA | NA | NA | NA | NA |
| rs966556 | 13 | 20749239 | C/T | PPIAP28 | 3.9 | 0.66 | 0.48 (0.4–0.7) | 8.31E−06 | 0.70 | 0.83 (0.5–1.4) | 0.49 | 0.56 (0.4–0.7) | 3.17E−05 | 66.9 | NA | NA | NA | NA | NA | NA |
| rs74032316 | 15 | 96571138 | T/C | RP11-4G2.1 | 0.2 | 0.24 | 2.30 (1.6–3.3) | 5.95E−06 | 0.24 | 1.05 (0.6–1.8) | 0.86 | 1.81 (1.3–2.4) | 1.10E−04 | 82.1 | NA | NA | NA | NA | NA | NA |
Chr chromosome, CI confidence interval, Dist distance, EAF effect allele frequency, Eff effect allele, I2 percentage of variants in the combined analysis that is attributable to study heterogeneity, NA not assessable, OR odds ratio, Ref reference allele.
aImputation quality > 85%. Median age at diagnosis 11.1 years (0.0–18.8); median age at audiological testing 11.8 years (0.3–19.0); median total cumulative dose cisplatin 480 mg/m2 (range: 40–950 mg/m2). Seventy-six (19.5%) patients had been treated with additional carboplatin. One hundred sixty-eight (43.1%) patients developed Muenster ≥ 2b hearing loss.
bMedian age at diagnosis 4.1 years (0.1–18.8); median cumulative dose cisplatin 400 mg/m2 (300–480 mg/m2). One hundred fifteen patients (59.9%) developed Muenster ≥ 2b hearing loss.
cMedian age at diagnosis 11.1 years (0.3–18.0); median cumulative dose of cisplatin 480 mg/m2 (83–770). Ninety-four survivors (50.0%) developed Muenster ≥ 2b hearing loss.
dNot assessable as more than 5% of the individuals had a missingness threshold lower than 0.9.