Table 2.
Summary of SNPs that showed genome-wide significant (P < 5 × 10−8) association with cup area (adjusted for disc area) in the combined analysis (n = 23,831 subjects with European and Asian descent)
| SNP | Chr. | Position | Annotation | Nearest gene | A1/A2 | Europeans MAF |
Asians MAF |
Combined (n = 23,831)
|
Heterogeneity
|
Disc area combined (n = 24,089)
|
|||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| β | SE | P-value | β (R) | P-value (R) | P-value | I2 | β | SE | P-value | ||||||||
| rs301801 | 1 | 8,495,945 | Intronic | RERE | c/t | 0.33 | 0.15 | 0.016 | 0.003 | 4.55 × 10−9 | 0.016 | 4.55 × 10−9 | 4.56 × 10−1 | 0 | 0.004 | 0.005 | 3.80 × 10−1 |
| rs3924048 | 1 | 12,614,848 | Intergenic | DHRS3a | g/a | 0.40 | 0.58 | −0.016 | 0.003 | 1.34 × 10−10 | −0.016 | 1.34 × 10−10 | 7.55 × 10−1 | 0 | −0.003 | 0.005 | 4.68 × 10−1 |
| rs2113818 | 2 | 12,890,860 | Intergenic | TRIB2a | t/c | 0.49 | 0.29 | 0.015 | 0.002 | 1.19 × 10−9 | 0.015 | 1.19 × 10−9 | 7.90 × 10−1 | 0 | 0.005 | 0.004 | 2.70 × 10−1 |
| rs2623325 | 3 | 99,131,755 | Intergenic | COL8A1 | a/c | 0.11 | 0.18 | 0.025 | 0.005 | 4.36 × 10−8 | 0.024 | 1.33 × 10−5 | 1.71 × 10−1 | 27.9 | 0.025 | 0.008 | 1.92 × 10−3 |
| rs7865618 | 9 | 22,031,005 | Intronic | CDKN2B-AS1 | g/a | 0.44 | 0.16 | −0.023 | 0.002 | 1.37 × 10−21 | −0.022 | 9.36 × 10−17 | 3.12 × 10−1 | 12.9 | −0.010 | 0.005 | 2.01 × 10−2 |
| rs3858145 | 10 | 70,011,838 | Regulatory | ATOH7 | g/a | 0.25 | 0.34 | −0.015 | 0.003 | 7.83 × 10−8 | −0.014 | 1.56 × 10−5 | 1.6 5× 10−1 | 18.6 | −0.090 | 0.005 | 5.14× 10−75 |
| rs1346 | 11 | 65,337,251 | Upstream | SSSCA1 | t/a | 0.19 | 0.34 | −0.019 | 0.003 | 1.78 × 10−9 | −0.019 | 7.50 × 10−9 | 4.02 × 10−1 | 4.4 | −0.020 | 0.006 | 3.84 × 10−4 |
| rs7972528 | 12 | 84,131,036 | Intergenic | TMTC2 | t/c | 0.47 | 0.11 | −0.014 | 0.003 | 4.03 × 10−8 | −0.011 | 9.34 × 10−3 | 8.02 × 10−3 | 55.4 | −0.020 | 0.005 | 4.24 × 10−5 |
| rs9546434 | 13 | 36,694,391 | Intronic | DCLK1 | t/c | 0.23 | 0.44 | 0.021 | 0.003 | 1.98 × 10−11 | 0.020 | 2.11 × 10−11 | 6.38 × 10−1 | 0 | −0.012 | 0.006 | 2.80 × 10−2 |
| rs10483727 | 14 | 61,072,875 | Upstream | SIX6 | t/c | 0.40 | 0.71 | 0.026 | 0.002 | 2.10 × 10−27 | 0.025 | 2.41 × 10−10 | 4.80 × 10−3 | 56.6 | −0.023 | 0.004 | 1.14 × 10−7 |
| rs11646917 | 16 | 51,428,908 | Intergenic | SALL1 | t/g | 0.27 | NA | −0.018 | 0.003 | 1.71 × 10−8 | −0.018 | 1.84 × 10−8 | 4.36 × 10−1 | 0.2 | −0.020 | 0.006 | 8.53 × 10−4 |
| rs11870935 | 17 | 45,732,605 | Intronic | KPNB1a | g/a | 0.47 | 0.35 | 0.013 | 0.002 | 1.57 × 10−8 | 0.013 | 1.57 × 10−8 | 5.81 × 10−1 | 0 | 0.001 | 0.004 | 8.82 × 10−1 |
| rs11651885 | 17 | 59,286,263 | Intronic | BCAS3a | g/a | 0.23 | 0.29 | −0.018 | 0.003 | 4.49 × 10−11 | −0.017 | 1.09 × 10−4 | 9.27 × 10−3 | 54.6 | 0.012 | 0.005 | 1.75×10−2 |
| rs6054383 | 20 | 6,584,604 | Intergenic | BMP2 | t/g | 0.42 | 0.61 | −0.015 | 0.002 | 2.13× 10−10 | −0.014 | 2.51 × 10−7 | 2.04 × 10−1 | 0 | 0.002 | 0.004 | 6.88 × 10−1 |
| rs1033667 | 22 | 2,9130,300 | Intronic | CHEK2 | t/c | 0.28 | 0.18 | −0.023 | 0.003 | 1.13 × 10−17 | −0.024 | 5.48 × 10−12 | 1.19 × 10−1 | 32.1 | −0.020 | 0.005 | 6.18 × 10−5 |
| rs1346786 | 2 | 56,108,333 | Intronic | EFEMP1a | t/c | 0.31 | 0.63 | −0.014 | 0.003 | 4.26 × 10−8 | −0.014 | 4.26 × 10−8 | 5.20 × 10−1 | 0 | 0.008 | 0.005 | 9.66 × 10−2 |
| rs6764184 | 3 | 58,006,266 | Intronic | FLNBa | t/g | 0.24 | 0.46 | 0.015 | 0.003 | 1.10 × 10−8 | 0.015 | 2.48 × 10−7 | 2.94 × 10−1 | 14.6 | 0.003 | 0.005 | 5.25 × 10−1 |
| rs1402538 | 6 | 122,388,851 | Intergenic | HSF2 | a/g | 0.38 | 0.40 | −0.014 | 0.002 | 4.33 × 10−9 | −0.014 | 4.33 × 10−9 | 7.51 × 10−1 | 0 | −0.015 | 0.004 | 8.57 × 10−4 |
| rs10846617 | 12 | 124,662,131 | Intronic | FAM101Aa | c/g | 0.44 | 0.28 | −0.014 | 0.002 | 7.17 × 10−10 | −0.014 | 7.17 × 10−10 | 4.71 × 10−1 | 0 | −0.003 | 0.004 | 5.31 × 10−1 |
| rs10130556 | 14 | 53,970,675 | Intronic | DDHD1/BMP4a | g/c | 0.41 | 0.47 | −0.014 | 0.002 | 4.53 × 10−9 | −0.014 | 4.53× 10−9 | 6.46 × 10−1 | 0 | 0.006 | 0.005 | 2.07 × 10−1 |
| rs11247230 | 15 | 101,197,005 | Intergenic | ASB7a | g/a | 0.34 | 0.71 | 0.014 | 0.003 | 1.34 × 10−8 | 0.014 | 1.34 × 10−8 | 8.46 × 10−1 | 0 | 0.017 | 0.004 | 1.41 × 10−4 |
| rs5756813 | 22 | 38,175,477 | Downstream | TRIOBPa | g/t | 0.39 | 0.34 | 0.014 | 0.002 | 1.49 × 10−9 | 0.014 | 1.49 × 10−9 | 9.61 × 10−1 | 0 | 0.013 | 0.004 | 2.39 × 10−3 |
We tested for heterogeneous effects, for which P-values and I2 are shown. Results for the combined meta-analysis for disc area are shown. The first 15 SNPs were genome-wide significant in stage 1 (meta-analysis of subjects with European descent); the last seven SNPs reached genome-wide significance in stage 3 (meta-analysis of subjects with European and Asian descent). SNP, single nucleotide polymorphism; nearest gene, reference NCBI build 37; A1, reference allele; A2, other allele; MAF, average minor allele frequency; NA, not available; β, effect size on disc area based on allele A1 based on a fixed-effect meta-analysis; β (R), effect size on cup area based on allele A1 based on a random-effect meta-analysis; P-value (R) is the P-value based on a random-effect meta-analysis; SE, standard error of the effect size.
Are the newly identified loci.