Table 1.
Summary of SNPs that showed genome-wide significant (P < 5 × 10−8) association with disc area in the combined analysis (n = 24,089 subjects with European and Asian descent)
| SNP | Chr. | Position | Annotation | Nearest Gene | A1/A2 | Europeans MAF |
Asians MAF |
Combined (n = 24,089)
|
Heterogeneity
|
Cup area combined (n = 23,831) |
|||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| β | SE | P-value | β (R) | P-value (R) | P-value | I2 | β | SE | P-value | ||||||||
| rs1192419 | 1 | 92,080,059 | Intergenic | CDC7/TGFBR3 | a/g | 0.18 | 0.19 | 0.087 | 0.006 | 7.98 × 10−56 | 0.087 | 7.98 × 10−56 | 8.51 × 10−1 | 0 | 0.006 | 0.003 | 4.58×10−2 |
| rs6671926 | 1 | 227,386,971 | Intronic | CDC42BPAa | a/g | 0.08 | 0.03 | −0.067 | 0.009 | 3.69 × 10−14 | −0.065 | 9.21 × 10−14 | 5.95 × 10−1 | 0 | 0.025 | 0.005 | 2.33×10−7 |
| rs9969524 | 8 | 88,746,846 | Intronic | DCAF4L2a | t/a | 0.46 | NA | 0.030 | 0.005 | 1.54 × 10−8 | 0.032 | 4.36 × 10−7 | 2.79 × 10−1 | 19.0 | 0.006 | 0.003 | 4.24×10−2 |
| rs1900004 | 10 | 70,000,881 | Intronic | ATOH7 | t/c | 0.23 | 0.26 | −0.097 | 0.005 | 1.13 × 10−73 | −0.097 | 7.27 × 10−39 | 6.43 × 10−2 | 40.4 | −0.016 | 0.003 | 4.92×10−8 |
| rs1362756 | 16 | 51,458,290 | Intergenic | SALL1 | c/g | 0.29 | 0.15 | 0.033 | 0.005 | 9.27 × 10−11 | 0.033 | 5.84 × 10−10 | 3.91 × 10−1 | 5.6 | 0.011 | 0.003 | 4.66×10−5 |
| rs12406092 | 1 | 169,543,131 | Intronic | F5a | a/g | 0.30 | 0.23 | 0.028 | 0.005 | 3.32 × 10−9 | 0.028 | 3.3 × 10−9 | 4.60 × 10−1 | 0 | 0.003 | 0.003 | 2.88×10−1 |
| rs1549733 | 2 | 218,472,172 | Intronic | DIRC3a | t/c | 0.21 | 0.21 | 0.031 | 0.005 | 4.03 × 10−9 | 0.031 | 4.03 × 10−9 | 6.74 × 10−1 | 0 | −0.001 | 0.003 | 6.99×10−1 |
| rs11129176 | 3 | 25,049,310 | Intronic | RARBa | a/g | 0.29 | 0.22 | 0.026 | 0.005 | 1.74 × 10−8 | 0.026 | 1.74 × 10−8 | 7.99 × 10−1 | 0 | 0.011 | 0.003 | 1.12×10−5 |
| rs9860250 | 3 | 100,637,871 | Intronic | ABI3BPa | g/a | 0.18 | 0.08 | −0.036 | 0.006 | 2.42 × 10−9 | −0.036 | 2.42 × 10−9 | 4.59 × 10−1 | 0 | −0.004 | 0.003 | 2.05×10−1 |
| rs11031436 | 11 | 31,663,882 | Intronic | ELP4a | t/a | 0.22 | 0.32 | 0.033 | 0.005 | 6.43 × 10−10 | 0.032 | 3.63 × 10−7 | 2.47 × 10−1 | 19.4 | 0.003 | 0.003 | 3.26×10−1 |
| rs1511589 | 12 | 84,061,431 | Intergenic | TMTC2a | a/g | 0.46 | 0.18 | −0.028 | 0.005 | 1.08 × 10−9 | −0.028 | 5.40 × 10−8 | 3.22 × 10−1 | 12.0 | −0.012 | 0.003 | 5.34×10−6 |
| rs8034595 | 15 | 96,719,229 | Intronic | NR2F2a | a/c | 0.28 | 0.30 | −0.026 | 0.005 | 2.54 × 10−8 | −0.026 | 2.54 × 10−8 | 4.99 × 10−1 | 0 | 0.003 | 0.003 | 2.20×10−1 |
| rs2412970 | 22 | 30,486,826 | Intronic | HORMAD2a | g/a | 0.43 | 0.41 | 0.024 | 0.004 | 3.40 × 10−8 | 0.024 | 3.40 × 10−8 | 6.75 × 10−1 | 0 | 0.007 | 0.002 | 3.52×10−3 |
| rs9607469 | 22 | 37,919,267 | Upstream gene variant | CARD10 | a/g | 0.15 | 0.23 | 0.041 | 0.006 | 2.29 × 10−13 | 0.041 | 1.31 × 10−8 | 1.17 × 10−1 | 32.3 | 0.005 | 0.003 | 1.03×10−1 |
We tested for heterogeneous effects, for which P-values and I2 are shown. Results for the combined meta-analysis of cup area are shown. The first five SNPs were genome-wide significant in stage 1 (meta-analysis of subjects with European descent); the last nine 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 disc 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.