Table 2. Genes demonstrating genome-wide significant evidence of rare variant association with type-1 diabetes on chromosome 6.
| Gene symbol | NCBI Build 37 chromosome 6 position (BP) | Number of rare variants | Unconditional analysisa | Conditional analysis: adjusted for lead MHC SNPb | ||
| Start | Stop | ZNORM | ZNORM | p | ||
| Very rare variation 0.1%<MAF<0.5% | ||||||
| HLA-DRB5 | 32,485,162 | 32,557,562 | 189 | 60.5 | 40.3 | 5.2×10−6 |
| Rare variation 0.5%<MAF<1% | ||||||
| GNL1 | 30,513,695 | 30,525,008 | 9 | 51.0 | 14.1 | 1.7×10−6 |
| DHX16 | 30,620,896 | 30,640,830 | 7 | 45.5 | 14.0 | 3.5×10−6 |
| C2 | 31,865,561 | 31,913,448 | 12 | 20.7 | 12.9 | 4.0×10−5 |
| CFB | 31,895,265 | 31,919,860 | 8 | 19.9 | 9.7 | 1.3×10−4 |
| TNXB | 32,008,931 | 32,077,151 | 21 | 29.9 | 34.5 | <1.7×10−6 |
| AK123889 | 32,223,487 | 32,233,615 | 18 | 41.2 | 24.1 | 1.0×10−4 |
| C6orf10 | 32,256,302 | 32,339,656 | 97 | 89.1 | 57.8 | 3.0×10−6 |
| BTNL2 | 32,362,512 | 32,374,900 | 6 | 26.0 | 15.7 | <1.7×10−6 |
| HLA-DRB5 | 32,485,162 | 32,557,562 | 62 | 43.2 | 29.4 | <1.7×10−6 |
| HLA-DRB6 | 32,520,489 | 32,552,155 | 34 | 44.1 | 27.6 | <2.5×10−6 |
| HLA-DQA2 | 32,709,162 | 32,715,219 | 6 | 28.6 | 13.1 | 2.3×10−5 |
| HLA-DQB2 | 32,723,875 | 32,731,330 | 6 | 18.5 | 17.0 | <1.7×10−6 |
| TAP2 | 32,781,499 | 32,806,547 | 18 | 21.8 | 18.9 | <1.7×10−6 |
| HLA-DMB | 32,902,409 | 32,908,817 | 8 | 10.3 | 8.2 | 2.8×10−5 |
| BRD2 | 32,936,436 | 32,949,281 | 13 | 14.9 | 11.2 | 8.7×10−6 |
| COL11A2 | 33,130,468 | 33,160,245 | 13 | 31.2 | 17.4 | 1.7×10−6 |
a
Genes with a permuted p-value less than 1.7×10−6 (indicating genome wide significance assuming a significance level of 5% and that there are 30,000 genes in the human genome [25]) in a Generalised C-alpha test.
b
For these genes, results are also shown when effects are adjusted for the lead common MHC SNP (rs9268645). Both analyses are adjusted for 3 principal components to account for population structure. For the unconditional analysis results are based on 600,000 permutations; for the conditional analysis results are based on 575,000 permutations. MAF, minor allele frequency; BP, base pair; MAF: Minor Allele Frequency; MHC, Major histocompatibility complex; NCBI, National Center for Biotechnology Information.