Tables
- TABLE 1
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.
