COL18A1 variants associated with serum endostatin (ES) levels, gene expression and clinical measures
| QTL data | ES β# | ES p-value | eQTL β¶ | eQTL p-value | FDR |
| EA subjects | |||||
| Omni5 array | |||||
| rs9976834 | −3510 | 0.0001983 | −0.66 | 2.22×10−197 | <1.34×10−5 |
| rs9976784 | −3205 | 0.0003702 | −0.666 | 2.27×10−200 | <1.34×10−5 |
| rs2838932 | −3137 | 0.0004473 | −0.636 | 1.17×10−184 | <1.34×10−5 |
| rs2236461 | −3089 | 0.0004758 | −0.643 | 4.78×10−191 | <1.34×10−5 |
| rs9977482 | −2903 | 0.0006399 | −0.705 | 9.81×10−254 | <1.34×10−5 |
| rs2236470 | −2864 | 0.0007104 | −0.707 | 2.57×10−255 | <1.34×10−5 |
| rs8133622 | −2988 | 0.0007197 | −0.632 | 1.27×10−182 | <1.34×10−5 |
| rs9980531 | −2947 | 0.0008603 | −0.625 | 5.94×10−177 | <1.34×10−5 |
| rs11702782 | −3139 | 0.001041 | −0.584 | 6.75×10−37 | <1.34×10−5 |
| rs12482088+ | −2758 | 0.001153 | −0.695 | 1.02×10−248 | <1.34×10−5 |
| rs201577993 | −2552 | 0.001393 | NA | NA | NA |
| rs2330180 | −2898 | 0.001514 | −0.632 | 5.80×10−180 | <1.34×10−5 |
| rs2236459 | −2475 | 0.001694 | −0.513 | 1.35×10−143 | <1.34×10−5 |
| rs2236464 | −2677 | 0.002145 | −0.654 | 1.06×10−196 | <1.34×10−5 |
| rs11702494 | −2567 | 0.00237 | −0.674 | 1.76×10−231 | <1.34×10−5 |
| rs2236451+ | −2289 | 0.00332 | −0.55 | 1.20×10−176 | <1.34×10−5 |
| rs55684533 | −2479 | 0.004203 | NA | NA | NA |
| rs10854470 | −1915 | 0.01018 | −0.445 | 1.32×10−122 | <1.34×10−5 |
| rs2236454 | −1902 | 0.01065 | −0.465 | 9.84×10−134 | <1.34×10−5 |
| rs4819124 | −1802 | 0.01436 | −0.367 | 1.74×10−86 | <1.34×10−5 |
| rs61633029 | −1864 | 0.02498 | −0.473 | 1.06×10−115 | <1.34×10−5 |
| rs17338076 | −2409 | 0.02935 | −0.674 | 1.38×10−34 | <1.34×10−5 |
| rs2236479 | −1641 | 0.03106 | −0.455 | 5.77×10−127 | <1.34×10−5 |
| rs2150443 | −1544 | 0.03625 | −0.367 | 2.40×10−86 | <1.34×10−5 |
| rs7409857 | −1531 | 0.03885 | −0.32 | 6.64×10−65 | <1.34×10−5 |
| rs7281138 | 1752 | 0.04298 | NA | NA | NA |
| WES | |||||
| rs9979845 | −2675 | 0.0013 | −0.705 | 9.81×10−254 | <1.34×10−5 |
| rs11702425 | −2107 | 0.0058 | −0.532 | 4.67×10−157 | <1.34×10−5 |
| rs749627 | −1682 | 0.022 | −0.304 | 6.79×10−58 | <1.34×10−5 |
| AA subjects | |||||
| Omni5 array | |||||
| rs4819124 | −5598 | 0.01829 | −0.367 | 1.74×10−86 | <1.34×10−5 |
| rs2150443 | −5415 | 0.0219 | −0.367 | 2.40×10−86 | <1.34×10−5 |
| rs73370840 | 6899 | 0.02508 | 0.31 | 1.30×10−23 | <1.34×10−5 |
| rs2838917 | −4931 | 0.02828 | 0.153 | 7.35×10−13 | <1.34×10−5 |
| rs114255716 | 10 260 | 0.0306 | NA | NA | NA |
| rs78620106 | 10 810 | 0.0308 | NA | NA | NA |
| rs61633029 | 5548 | 0.03098 | −0.473 | 1.06×10−115 | <1.34×10−5 |
| rs56327327 | −4398 | 0.04565 | NA | NA | NA |
| WES | |||||
| rs749627 | 5172 | 0.025 | −0.304 | 6.79×10−58 | <1.34×10−5 |
| Phenotypic data§ | Clinical measure | Effect estimateƒ | p-value |
| EA subjects | |||
| rs7499 | Survival | 0.77 (0.62–0.96)¶¶ | 0.018 |
| rs1050351 | Survival | 0.76 (0.61–0.95)¶¶ | 0.015 |
| rs1131100 | 6MWD (m) | 30.61 (2.09–59.13)++ | 0.035 |
| rs1131101 | 6MWD (m) | 30.61 (2.09–59.13)++ | 0.035 |
| rs2236467 | 6MWD (m) | 30.16 (1.80–58.53)++ | 0.037 |
| rs1131102 | 6MWD (m) | 30.11 (1.72–58.49)++ | 0.038 |
| rs2236466 | 6MWD (m) | 28.49 (−0.02–57.01)++ | 0.050 |
| rs7281138## | Cardiac index (L·min−1·m−2) | −0.11 (−0.23– −0.004)§§ | 0.043 |
| rs2838917## | Cardiac index (L·min−1·m−2) | −0.12 (−0.23– −0.01)§§ | 0.028 |
| rs2230688 | Cardiac index (L·min−1·m−2) | 0.19 (0.04–0.33)§§ | 0.010 |
| rs2230687 | Cardiac index (L·min−1·m−2) | 0.19 (0.05–0.33)§§ | 0.009 |
| rs2236456 | Cardiac index (L·min−1·m−2) | 0.14 (0.002–0.28)§§ | 0.047 |
QTL: quantitative trait locus; eQTL: expression QTL; FDR: false discovery rate; EA: European ancestry; WES: whole exome sequencing; AA: African ancestry; 6MWD: 6-min walk distance; NA: no association between variant and gene expression. #: ES β-coefficients (protein QTL analysis) reflect differences in ES in pg·mL−1 for each copy of the minor allele; linear regressions on ES levels are adjusted for age and sex. ¶: eQTL β-coefficients reflect differences in robust multi-array analysis, a measure of intensity derived from Affymetrix gene expression data; methods for eQTL models have been previously published [11]. +: single nucleotide polymorphism (SNP) that appears on both Omni5 and WES arrays. §: phenotypic data are reported for EA only. ƒ: effect estimates are hazard ratios for associations with survival and β-coefficients for associations with all other clinical measures; coefficients reflect differences in clinical measures for subjects with the presence versus the absence of the minor allele. ##: SNP from Omni5 array; all others in the phenotypic data section are WES SNPs. ¶¶: associations with survival are adjusted for age at enrolment, sex, pulmonary arterial hypertension (PAH) subtype and PAH therapies, and additionally for difference in time from PAH diagnosis to cohort enrolment. ++: associations with 6MWD are adjusted for body mass index and the following comorbid conditions: hypertension, diabetes, obstructive lung disease, cardiomyopathy and chronic kidney disease. §§: associations with cardiac index are adjusted for age at enrolment, sex, PAH subtype and PAH therapies.