Table 3.
Results of gene burden tests comparing the frequency of variants in BLK, KLF11, and PAX4 in a disease cohort with that in a population cohort
| Variant type | Gene | Allele count in MODY cohort | Allele frequency in MODY cohort | Allele count in population cohort (UK Biobank) | Allele frequency in population cohort (UK Biobank) | OR (95% CI) | P | Prior probability | BFDP |
|---|---|---|---|---|---|---|---|---|---|
| Ultra-rare PTV | BLK | 1 | 4.10 × 10−4 | 14 | 3.77 × 10−5 | 10 (0.26–71) | 0.09 | 0.2 | 0.71 |
| KLF11 | 0 | 0 | 15 | 4.03 × 10−5 | 0 (0–39) | 1 | 0.2 | 0.8 | |
| PAX4 | 0 | 0 | 6 | 1.61 × 10−5 | 0 (0–97) | 1 | 0.2 | 0.8 | |
| HNF1A | 15 | 6.11 × 10−3 | 3 | 8.07 × 10−6 | 762 (215–4,108) | 1.37 × 10−30 | 0.2 | 1.20 × 10−9 | |
| HNF4A | 3 | 1.22 × 10−3 | 2 | 5.38 × 10−6 | 228 (26–2,724) | 2.79 × 10−6 | 0.2 | 0.03 | |
| Ultra-rare missense variants | BLK | 1 | 4.10 × 10−4 | 141 | 3.79 × 10−4 | 1 (0.03–6.00) | 0.6 | 0.2 | 0.82 |
| KLF11 | 2 | 8.10 × 10−4 | 122 | 3.28 × 10−4 | 2.5 (0.3–9.0) | 0.2 | 0.2 | 0.78 | |
| PAX4 | 2 | 8.10 × 10−4 | 84 | 2.26 × 10−4 | 3.6 (0.43–13.00) | 0.1 | 0.2 | 0.70 | |
| HNF1A | 21 | 8.56 × 10−3 | 102 | 2.74 × 10−4 | 31 (19–51) | 1.70 × 10−23 | 0.2 | 5.80 × 10−38 | |
| HNF4A | 14 | 5.70 × 10−3 | 83 | 2.23 × 10−4 | 26 (13–46) | 4.41 × 10−15 | 0.2 | 1.20 × 10−25 |
The frequency of ultra-rare (allele count = 1) PTV and missense variants in a MODY cohort (n = 1,227) was compared with the frequency in the UK Biobank population cohort (n = 185,898).