Table 2.
Candidate genes for association with MacTel based on established co-morbidity with HSAN/CMT
| Genes | Qualified variants in MacTel cases [n=793] | Qualified variants in controls [n=17610] | Excess QV | FET P | OR | Collapsing Model | Disease association [dominant] [recessive] |
|---|---|---|---|---|---|---|---|
| SLC25A46 | 4 | 5 | 0.0024 | 3.6 x 10−4 | 17.7 | 1a | hereditary motor and sensory neuropathy, type VIB [rec] |
| SCN11A | 9 | 53 | 0.0042 | 0.001 | 3.8 | 1b | hereditary sensory and autonomic neuropathy, type VII [dom] |
| PHYH | 6 | 32 | 0.0029 | 0.005 | 4.2 | 2a | Refsum disease [rec] |
| DCTN1 | 6 | 39 | 0.0027 | 0.012 | 3.5 | 1a | distal hereditary motor neuropathy, type VIIB [dom] |
| MFN2 | 7 | 55 | 0.0029 | 0.016 | 2.9 | 2b | CMT, axonal, 2A2A [dom], hereditary motor and sensory neuropathy VIA [dom] |
| Combined | 0.015 | ||||||
| SPTLC1 | 1 | 14 | 0.0002 | 0.484 | 1.6 | 1a | hereditary sensory and autonomic neuropathy, type IA [dom] |
| SPTLC2 | 2 | 11 | 0.0009 | 0.106 | 4.0 | 1b | hereditary sensory and autonomic neuropathy, type IC [dom] |
Collapsing models and filtering criteria are specified in Supplementary Table 1. In short, Models 1a and 1b included only variants absent from gnomAD (“ultra rare”) and filtered for pathogenicity by PolyPhen as “probably pathogenic” (Model 1a) or REVEL >0.5 (Model 1b). Models 2a/b and 3a/b had the same pathogenicity filtering criteria and gnomAD minor allele frequencies <0.00005 (“very rare”) and <0.001 (“rare”), respectively.