Table 2. Selected SNPs from the pooled GWAS comparing responders and non-responders at 6 months ranibuzimab treatment and validation results using an independent genotyping technique in the Melbourne discovery cohort.
| SNP | Chr. | Position+ | Gene | Effect Allele | Pooled GWAS |
Technical Replication |
||
|---|---|---|---|---|---|---|---|---|
| Pooled GWAS SNPs reaching P ≤ 9 × 10−8 | P Value | OR | P Value | OR (95% CI) | ||||
| rs4910623 | 11 | 4389639 | OR52B4 | G | 3.69 × 10−9 | 3.14 | 5.65 × 10−5 | 2.58 (1.63–4.10) |
| rs323085 | 18 | 49290621 | LOC100287225 | C | 3.29 × 10−8 | 0.22 | 6.53 × 10−4 | 0.16 (0.06–0.46) |
| rs10158937 | 1 | 66144876 | LEPR | C | 5.36 × 10−8 | 0.28 | 1.30 × 10−3 | 0.32 (0.17–0.65) |
| rs2475779 | 5 | 157541895 | CLINT1 | T | 1.59 × 10−9 | 0.29 | 1.36 × 10−3 | 0.40 (0.23–0.70) |
| rs59741976 | 3 | 74593662 | CNTN3 | T | 2.65 × 10−8 | 0.32 | 1.84 × 10−3 | 0.31 (0.15–0.65) |
| rs4655583 | 1 | 66155407 | LEPR | A | 1.37 × 10−8 | 0.28 | 2.38 × 10−3 | 0.34 (0.17–0.69) |
| rs7857431 | 9 | 132529504 | PTGES | T | 3.36 × 10−8 | 0.25 | 4.58 × 10−3 | 0.12 (0.03–0.53) |
| rs794009 | 4 | 40139719 | N4BP2 | A | 6.91 × 10−8 | 0.35 | 5.47 × 10−3 | 0.40 (0.22–0.77) |
| rs10234065 | 7 | 19547138 | TWISTNB | T | 1.37 × 10−8 | 0.31 | 5.61 × 10−3 | 0.13 (0.03–0.56) |
| rs1447830 | 3 | 74613171 | CNTN3 | T | 7.56 × 10−9 | 0.30 | 5.63 × 10−3 | 0.35 (0.17–0.74) |
| rs2110470 | 7 | 19509870 | TWISTNB | A | 3.35 × 10−8 | 0.35 | 5.65 × 10−3 | 0.40 (0.21–0.77) |
| rs1892535 | 1 | 66097181 | LEPR | T | 6.50 × 10−8 | 0.31 | 6.50 × 10−3 | 0.38 (0.19–0.77) |
| rs1573317 | 18 | 382268 | COLEC12 | T | 1.11 × 10−9 | 0.27 | 7.60 × 10−3 | 0.36 (0.18–0.77) |
| rs13154178 | 5 | 42828101 | SEPP1 | A | 2.09 × 10−8 | 0.36 | 8.20 × 10−3 | 0.49 (0.30–0.83) |
| rs4909963 | 11 | 11119228 | GALNTL4 | T | 9.85 × 10−9 | 0.24 | 8.32 × 10−3 | 0.20 (0.06–0.67) |
| rs79966776 | 3 | 74582701 | CNTN3 | A | 1.61 × 10−8 | 0.32 | 9.72 × 10−3 | 0.42 (0.22–0.81) |
| rs510549 | 3 | 111700305 | ABHD10 | T | 1.60 × 10−9 | 0.34 | 1.07 × 10−2 | 0.53 (0.33–0.87) |
| rs6917419 | 6 | 27243480 | PRSS16 | T | 3.80 × 10−8 | 0.33 | 1.41 × 10−2 | 0.32 (0.13–0.80) |
| rs12117294 | 1 | 209814879 | LAMB3 | T | 1.89 × 10−8 | 0.34 | 1.84 × 10−2 | 0.46 (0.25–0.88) |
| rs10767060 | 11 | 23468443 | LOC100500938 | T | 8.72 × 10−8 | 0.38 | 2.23 × 10−2 | 0.58 (0.37–093) |
| rs17770298 | 9 | 101208288 | GABBR2 | A | 7.44 × 10−9 | 0.18 | 2.40 × 10−2 | 0.19 (0.05–081) |
| rs11131078 | 3 | 7548067 | GRM7 | T | 3.23 × 10−9 | 0.13 | 2.63 × 10−2 | 0.58 (0.37–0.94) |
| rs292998 | 5 | 58032485 | RAB3C | G | 3.86 × 10−9 | 0.38 | 2.94 × 10−2 | 0.61 (0.39–0.95) |
| rs772433 | 2 | 7838257 | LOC339788 | A | 5.06 × 10−8 | 0.36 | 4.24 × 10−2 | 0.62 (0.40–0.98) |
| rs3806586 | 2 | 128433897 | LIMS2 | T | 1.16 × 10−9 | 0.26 | 4.96 × 10−2 | 0.52 (0.28–1.00) |
| rs9644866 | 9 | 2290590 | SMARCA2 | T | 3.72 × 10−9 | 0.17 | 5.60 × 10−2 | 0.63 (0.40–1.01) |
| rs10050214 | 4 | 78733015 | CNOT6L | T | 4.22 × 10−8 | 0.38 | 6.35 × 10−2 | 0.40 (0.28–1.04) |
| rs12638297 | 3 | 29748169 | RBMS3 | T | 4.29 × 10−8 | 0.31 | 6.40 × 10−2 | 0.50 (0.25–1.04) |
| rs4449299 | 3 | 14598965 | GRIP2 | A | 5.50 × 10−8 | 0.39 | 8.79 × 10−2 | 0.64 (0.39–1.07) |
| rs1353892 | 12 | 90716019 | C12orf37 | T | 1.06 × 10−9 | 0.34 | 9.71 × 10−2 | 0.67 (0.42–1.07) |
| rs659910 | 11 | 131769454 | NTM | T | 1.27 × 10−8 | 0.39 | 1.67 × 10−1 | 0.71 (1.00–1.03) |
| rs10141328 | 14 | 96752555 | ATG2B | C | 7.78 × 10−8 | 0.16 | 1.90 × 10−1 | 0.73 (0.47–1.16) |
| rs9323992 | 14 | 98649816 | C14orf64 | T | 4.59 × 10−8 | 0.38 | 5.14 × 10−1 | 0.84 (0.50–1.41) |
| rs7432690 | 3 | 77450363 | ROBO2 | T | 9.91 × 10−10 | 0.14 | 6.81 × 10−1 | 1.09 (0.72–1.67) |
| rs141659302 | 11 | 128802177 | TP53AIP1 | T | 3.79 × 10−8 | 0.41 | 9.99 × 10−1 | 0.74 (0.00–0.00) |
| rs7320683 | 13 | 71787948 | DACH1 | A | 5.38 × 10−8 | 2.86 | 1.00 | 1 (−) |
| rs291477 | 3 | 73807858 | PDZRN3 | G | 1.85 × 10−10 | 2.91 | 1.00 | 1 (−) |
| Pooled GWAS SNPs in known pharmagenes showing suggestive significance | ||||||||
| rs3804938 | 3 | 7550294 | GRM7 | C | 1.35 × 10−7 | 0.13 | 1.01 × 10−2 | 0.54 (0.34–0.87) |
| rs4148732 | 7 | 87234049 | ABCB1 | G | 2.72 × 10−6 | 0.22 | 1.00 × 10−3 | 0.08 (0.02–0.38) |
| Pooled GWAS SNPs leading to a missense change in gene | ||||||||
| rs3877899 | 5 | 42801268 | SEPP1 | A | 9.02 × 10−7 | 0.36 | 1.15 × 10−3 | 0.34 (0.18–0.66) |
| rs34677 | 5 | 33998768 | AMACR | T | 3.22 × 10−5 | 0.35 | 3.0 × 10−3 | 0.26 (0.11–064) |
| rs3784588 | 15 | 31294654 | TRPM1 | T | 4.73 × 10−5 | 0.27 | 9.96 × 10−1 | 0.04 (1.00–1.03) |
| rs17659179 | 18 | 47511113 | MYO5B | A | 8.20 × 10−5 | 0.28 | 4.75 × 10−2 | 0.29 (0.09–0.99) |
| rs17673268 | 9 | 368128 | DOCK8 | T | 1.54 × 10−5 | 0.41 | 2.44 × 10−1 | 0.63 (1.00–1.03) |
For technical replication P values were calculated using logistic regression adjusted for baseline visual acuity, OR = odds ratio, SNP: single nucleotide polymorphism, Chr: chromosome, BP: base pair position on chromosome. SNPs that remained significantly associated after Bonferroni correction for multiple testing are highlighted in bold. +Representing position from phase 3 1000 G CEU reference panel.