Table 1. Replication of likely-causal associations between rare coding variants and height.
P-values and effect sizes are compared for the 28 height-associated variants that were included in the ExomeChip analysis previously performed by Marouli et al.2 Effect directions replicated for all 28 variants, most of which had not previously reached exome-wide significance. The last column indicates whether any variants in the affected gene had previously reached significance; several implicated genes were novel relative to Marouli et al.
| Height variants reaching exome-wide significance in Marouli et al. (2017) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| SNP | Cytoband | Gene | Variant effect |
MAF (UKB) |
P-value (UKB) |
P-value (Marouli et al.) |
Effect size (s.e.) (UKB) |
Effect size (s.e.) (Marouli et al.) |
Effect sign agreement |
Gene reported |
| rs143365597 | 1p34.2 | SCMH1 | missense | 4.4E-03 | 6.10E-38 | 1.60E-25 | 0.149 (0.012) | 0.190 (0.018) | ✓ | ✓ |
| rs144673025 | 1q41 | DISP1 | missense | 7.3E-03 | 1.60E-13 | 1.10E-09 | −0.063 (0.009) | −0.078 (0.013) | ✓ | ✓ |
| rs142036701 | 2q35 | IHH | missense | 3.8E-04 | 9.30E-10 | 1.10E-15 | −0.234 (0.044) | −0.320 (0.040) | ✓ | ✓ |
| rs149385790 | 4q26 | PDE5A | missense | 1.1E-03 | 1.80E-14 | 7.50E-17 | 0.194 (0.026) | 0.260 (0.031) | ✓ | ✓ |
| rs778920303 | 5p13.3 | NPR3 | missense | 2.5E-03 | 3.60E-29 | 1.10E-08 | 0.177 (0.016) | 0.130 (0.022) | ✓ | ✓ |
| rs61736454 | 5q12.3 | ADAMTS6 | missense | 2.6E-03 | 5.30E-24 | 7.80E-09 | −0.151 (0.016) | −0.150 (0.026) | ✓ | ✓ |
| rs78727187 | 5q23.3 | FBN2 | missense | 6.6E-03 | 1.20E-49 | 2.50E-33 | 0.139 (0.010) | 0.180 (0.015) | ✓ | ✓ |
| rs148833559 | 5q35.2 | STC2 | missense | 1.3E-03 | 9.10E-40 | 5.70E-15 | 0.285 (0.022) | 0.290 (0.037) | ✓ | ✓ |
| rs75596750 | 8q24.22 | ZFAT | cryptic splice | 8.0E-04 | 6.50E-23 | 1.50E-12 | 0.264 (0.028) | 0.250 (0.036) | ✓ | ✓ |
| rs138273386 | 11p14.2 | FIBIN | missense | 4.3E-03 | 2.40E-10 | 5.80E-12 | −0.078 (0.013) | −0.120 (0.017) | ✓ | ✓ |
| rs141308595 | 15q26.1 | HAPLN3 | missense | 1.4E-03 | 7.40E-46 | 2.80E-13 | −0.307 (0.022) | −0.27 (0.037) | ✓ | ✓ |
| Height variants not reaching exome-wide significance in Marouli et al. (2017) | ||||||||||
| SNP | Cytoband | Gene | Variant effect |
MAF (UKB) |
P-value (UKB) |
P-value (Marouli et al.) |
Effect size (s.e.) (UKB) |
Effect size (s.e.) (Marouli et al.) |
Effect sign agreement | Gene reported |
| rs121908188 | 1p36.11 | SEPN1 | missense | 8.8E-04 | 4.80E-11 | 1.10E-01 | −0.178 (0.028) | −0.088 (0.055) | ✓ | |
| rs200496074 | 1p35.2 | COL16A1 | missense | 6.5E-03 | 1.10E-10 | 2.90E-01 | 0.065 (0.010) | 0.063 (0.015) | ✓ | |
| rs201166538 | 3q13.33 | LRRC58 | missense | 1.7E-04 | 6.70E-20 | 1.00E-01 | 0.545 (0.061) | 0.097 (0.092) | ✓ | |
| rs143137713 | 3q24 | GYG1 | missense | 2.4E-03 | 1.00E-10 | 1.70E-01 | −0.101 (0.017) | −0.049 (0.036) | ✓ | |
| rs73181210 | 3q26.2 | PHC3 | missense | 7.2E-03 | 9.00E-11 | 1.10E-05 | 0.066 (0.009) | 0.056 (0.013) | ✓ | ✓ |
| rs149437411 | 3q27.3-q28 | LPP | missense | 3.2E-03 | 2.00E-15 | 1.70E-05 | 0.122 (0.015) | 0.088 (0.020) | ✓ | |
| rs147927477 | 6p21.32 | COL11A2 | missense | 6.8E-04 | 9.30E-12 | 9.90E-01 | −0.215 (0.031) | −0.001 (0.049) | ✓ | |
| rs146458902 | 7p14.1 | GLI3 | missense | 6.1E-03 | 1.10E-15 | 3.50E-04 | 0.080 (0.010) | 0.060 (0.017) | ✓ | ✓ |
| rs121912974 | 7q11.23 | POR | missense | 3.8E-04 | 5.70E-10 | 1.20E-03 | 0.271 (0.042) | 0.180 (0.057) | ✓ | |
| rs140870470 | 9p13.3 | NPR2 | missense | 4.4E-04 | 1.80E-11 | 1.40E-01 | 0.251 (0.039) | 0.160 (0.110) | ✓ | ✓ |
| rs143836544 | 9q34.11 | LRRC8A | missense | 6.1E-03 | 3.20E-09 | 2.00E-05 | −0.060 (0.011) | −0.065 (0.015) | ✓ | ✓ |
| rs200733908 | 11q13.1 | LTBP3 | missense | 4.7E-04 | 8.10E-12 | 4.00E-01 | −0.281 (0.042) | −0.059 (0.070) | ✓ | ✓ |
| rs202116412 | 12p13.1 | APOLD1 | splice donor | 1.3E-03 | 3.80E-09 | 3.40E-06 | 0.131 (0.024) | 0.110 (0.024) | ✓ | ✓ |
| rs142153001 | 14q11.2 | LRP10 | missense | 9.0E-03 | 1.20E-11 | 5.00E-03 | 0.057 (0.009) | 0.035 (0.013) | ✓ | ✓ |
| rs201029932 | 14q22.2 | SAMD4A | missense | 4.8E-03 | 8.60E-13 | 6.80E-04 | −0.080 (0.012) | −0.057 (0.017) | ✓ | ✓ |
| rs35816944 | 16p13.3 | SPSB3 | missense | 6.7E-03 | 1.10E-18 | 2.90E-05 | −0.083 (0.010) | −0.067 (0.016) | ✓ | ✓ |
| rs141510764 | 16q23.1 | CLEC3A | missense | 3.7E-04 | 3.20E-09 | 9.10E-04 | 0.230 (0.042) | 0.260 (0.077) | ✓ | ✓ |