Table 2.
Enrichment of ultra-rare variants in HOX genes in non-syndromic clubfoot cases
| Gene/Pathway | VAR_TYPE | Enrichment versus gnomAD | Enrichment versus in-house control | |||||
| P_DOM | CASE (n=857) | CONTROL (n=56 885) | P_DOM | CASE (n=857) | CONTROL (n=1043) | |||
| Limb HOX gene | HOXA9 | Missense | 7.71E-02 | 2 | 29 | 4.27E-01 | 2 | 1 |
| HOXA10 | All | 4.97E-01 | 1 | 45 | 1 | 0 | 1 | |
| HOXA11 | All | 3.12E-01 | 1 | 24 | 4.51E-01 | 1 | 0 | |
| HOXA13 | All | 2.70E-01 | 1 | 20 | 4.51E-01 | 1 | 0 | |
| HOXB9 | Missense | 4.25E-01 | 1 | 36 | 4.51E-01 | 1 | 0 | |
| HOXC9 | Missense | 4.58E-01 | 1 | 40 | 6.99E-01 | 1 | 1 | |
| HOXC10 | Missense | 9.96E-02 | 2 | 34 | 2.03E-01 | 2 | 0 | |
| HOXC11 | Missense | 1.29E-01 | 2 | 40 | 4.27E-01 | 2 | 1 | |
| HOXC12 | Missense | 5.20E-01 | 1 | 48 | 6.99E-01 | 1 | 1 | |
| HOXC13 | All | 3.32E-01 | 1 | 26 | 6.99E-01 | 1 | 1 | |
| HOXD9 | Missense | 1 | 0 | 20 | 1 | 0 | 1 | |
| HOXD10 | Missense | 1 | 0 | 33 | 1 | 0 | 2 | |
| HOXD11 | Missense | 1 | 0 | 25 | NA | 0 | 0 | |
| HOXD12 | Missense | 1.50E-02 | 3 | 32 | 1.86E-02 | 5 | 0 | |
| Combined (HOX9–13) | 1.96E-03 | 16 | 452 | 2.92E-02 | 17 | 9 | ||
| Non-limb HOX genes (HOX1–8) (combined) | 7.71E-01 | 10 | 806 | 7.66E-01 | 15 | 22 | ||
| Autism gene set | 5.16E-01 | 125 | 8296 | 5.58E-01 | 136 | 167 | ||
CASE, count in cases; CONTROL, count in controls; gnomAD TRAPD, TRAPD assay using gnomAD non-Finish European data; in-house TRAPD, TRAPD assay using in-house Caucasian controls; Limb HOX, posterior HOX genes (HOX9–13); NA, not available; Non-limb HOX, non-posterior HOX genes (HOX1–8); P_DOM, p value in dominant mode of TRAPD.