Table 2.
Genome-wide significant loci in the multi-ancestry meta-analysis of Fuchs Endothelial Corneal Dystrophy (FECD)
| rsID | Chr:Pos | Predicted causal gene | EA/ NEA | EAF | N case | N | OR [95% CI] | P-value | Direction | |
|---|---|---|---|---|---|---|---|---|---|---|
| Novel loci (P < 5 × 10−8) | ||||||||||
| rs11590557 | 1:54,324,099 | SSBP3 | A/G | 0.04 | 3655 | 258,564 | 1.61, [1.43 1.81] | 6.86 × 10−15 | +?+ | |
| rs74882680 | 7:11,700,254 | THSD7A | G/A | 0.02 | 3655 | 258,564 | 1.72 [1.48, 2.00] | 2.78 × 10−12 | +?+ | |
| rs150990106 | 7:107,955,927 | LAMB1 | A/G | 0.02 | 3655 | 258,564 | 1.75 [1.45, 2.10] | 4.33 × 10−9 | +?+ | |
| rs1138714 | 11:825,110 | PIDD1 | G/A | 0.53 | 3970 | 337,764 | 1.22 [1.16, 1.28] | 3.01 × 10−14 | +++ | |
| rs12439253 | 15:60,764,393 | RORA | T/G | 0.08 | 3970 | 337,764 | 1.29 [1.18, 1.40] | 4.31 × 10−9 | +-+ | |
| rs9303111 | 17:14,663,407 | HS3ST3B1 | C/A | 0.32 | 3970 | 337,764 | 0.81 [0.76, 0.85] | 1.17 × 10−13 | --- | |
| rs141208202 | 20:62,322,048 | LAMA5 | T/C | 0.05 | 3655 | 258,564 | 1.40 [1.25, 1.57] | 1.42 × 10−8 | +?+ | |
| rs114065856 | 21:45,432,844 | COL18A1 | T/C | 0.04 | 3970 | 337,764 | 0.61 [0.52, 0.72] | 2.87 × 10−9 | --- | |
| Previously reported loci | ||||||||||
| rs79742895 | 1:62,317,189 | KANK4 | C/T | 0.04 | 3655 | 258,564 | 1.78 [1.59, 1.98] | 1.78 × 10−24 | +?+ | |
| rs1200114 | 1:169,091,251 | ATP1B1 | A/G | 0.66 | 3970 | 337,764 | 0.73 [0.69, 0.77] | 5.38 × 10−34 | --- | |
| rs2093985 | 1:183,125,187 | LAMC1 | T/C | 0.54 | 3970 | 337,764 | 0.80 [0.76, 0.84] | 2.58 × 10−18 | --- | |
| rs11659764 | 18:55,668,281 | TCF4 | A/T | 0.05 | 3655 | 258,564 | 7.15 [6.60, 7.74] | 8.60 × 10−509 | +?+ | |
Genomic risk loci from the meta-analysis of MVP European and African cohorts plus Afshari et al.14. We identified eight novel FECD loci and replicated all four previously reported loci. rs1138714 previously reached suggestive significance in Afshari et al. at P = 7 × 10−7. Genomic coordinates correspond to GRCh38. EA, effect allele; NEA, non-effect allele; EAF, effect allele frequency; OR [95% CI], odds ratio with lower and upper bounds of 95% confidence interval; Direction, SNP effect direction from MVP EUR, MVP AFR, and Afshari et al. meta-analysis cohorts, respectively; “?” indicates the AFR variant did not meet the allele frequency cutoff of 1% and was not included. Additional details can be found in Supplementary Data 3.