TWAS / FUSION

GTEx v8 vs v7

All analyses were conducted by Junghyun Jung in the Mancuso lab

Table 1: Model heritability

Heritability estimates across all genes in each tissue study from GTEx v8 versus v7. Cis-locus was defined as +/-500kb of the gene boundary, GTEx defined QC parameters were used for individuals/SNPs and covariates, heritability was estimated using GCTA/REML.

N: number of samples; tot: number of converged genes with heritabiliy estimates; hsq: mean heritability estimate; hsq (se): standard error of the mean heritability estimate; hsq P<0.01: number of genes with heritability p-value < 0.01 (computed by likelihood ratio test), representing nominally predictive models.

  v8 (ALL)         v8 (EUR)         v7        
  N tot hsq hsq (se) hsq P<0.01 N tot hsq hsq (se) hsq P<0.01 N tot hsq hsq (se) hsq P<0.01
AVERAGE 310 22999 0.089 0.001 6753 260 22843 0.087 0.001 6125 214 22232 0.086 0.001 4909
Adipose - Subcutaneous 581 23395 0.089 0.001 10808 479 23292 0.088 0.001 9904 385 22570 0.09 0.001 8193
Adipose - Visceral (Omentum) 469 23317 0.079 0.001 8682 393 23127 0.079 0.001 7918 313 22410 0.077 0.001 6174
Adrenal Gland 233 22408 0.087 0.001 5729 194 22190 0.086 0.001 5014 175 21608 0.094 0.001 4521
Artery - Aorta 387 22481 0.099 0.001 8741 329 22473 0.092 0.001 7943 267 21651 0.094 0.001 6463
Artery - Coronary 213 22850 0.075 0.001 4606 175 22600 0.076 0.001 3984 152 21796 0.079 0.001 3248
Artery - Tibial 584 22059 0.095 0.001 10575 476 21944 0.094 0.001 9700 388 21238 0.097 0.001 8224
Brain - Amygdala 129 22257 0.071 0.001 2810 119 22188 0.071 0.001 2660 88 21523 0.076 0.001 1837
Brain - Anterior cingulate cortex (BA24) 147 22540 0.08 0.001 3748 135 22413 0.079 0.001 3512 109 21714 0.082 0.001 2710
Brain - Caudate (basal ganglia) 194 22768 0.099 0.001 5513 172 22604 0.098 0.001 5128 144 22461 0.081 0.001 3661
Brain - Cerebellar Hemisphere 175 23369 0.128 0.001 6612 157 23129 0.128 0.001 6200 125 22763 0.109 0.001 4408
Brain - Cerebellum 209 23922 0.125 0.001 7829 188 23815 0.124 0.001 7387 154 22835 0.128 0.001 5855
Brain - Cortex 205 23074 0.102 0.001 6073 183 22855 0.102 0.001 5695 136 22426 0.094 0.001 4012
Brain - Frontal Cortex (BA9) 175 22532 0.099 0.001 5005 157 22283 0.099 0.001 4603 118 22303 0.086 0.001 3144
Brain - Hippocampus 165 22055 0.084 0.001 3840 150 21835 0.084 0.001 3613 111 21685 0.073 0.001 2295
Brain - Hypothalamus 170 22922 0.077 0.001 3844 156 22701 0.078 0.001 3611 108 22590 0.069 0.001 2315
Brain - Nucleus accumbens (basal ganglia) 202 22980 0.091 0.001 5483 181 22838 0.091 0.001 5086 130 22688 0.08 0.001 3240
Brain - Putamen (basal ganglia) 170 21739 0.099 0.001 4748 153 21526 0.099 0.001 4362 111 21489 0.087 0.001 2818
Brain - Spinal cord (cervical c-1) 126 22893 0.082 0.001 3391 115 22806 0.083 0.001 3178 83 22112 0.085 0.001 2006
Brain - Substantia nigra 114 22103 0.076 0.001 2587 100 21843 0.077 0.001 2302 80 21390 0.079 0.001 1604
Breast - Mammary Tissue 396 24117 0.076 0.001 7681 329 24105 0.07 0.001 6708 251 22987 0.075 0.001 5044
Skin - Transformed fibroblasts 483 20752 0.117 0.001 10401 403 20569 0.116 0.001 9686 300 20086 0.109 0.001 7353
Blood - EBV-transformed lymphocytes 147 21318 0.083 0.001 3500 113 21072 0.083 0.001 2844 117 20692 0.084 0.001 2758
Colon - Sigmoid 318 22903 0.088 0.001 7260 266 22693 0.089 0.001 6561 203 22114 0.084 0.001 4874
Colon - Transverse 368 23410 0.086 0.001 7803 294 23362 0.08 0.001 6657 246 22709 0.076 0.001 5316
Esophagus - Gastroesophageal Junction 330 22703 0.09 0.001 7509 275 22407 0.09 0.001 6799 213 21542 0.084 0.001 4888
Esophagus - Mucosa 497 22607 0.096 0.001 10086 411 22454 0.095 0.001 9251 358 21741 0.098 0.001 8061
Esophagus - Muscularis 465 22503 0.099 0.001 9828 385 22282 0.099 0.001 8962 335 21673 0.096 0.001 7773
Heart - Atrial Appendage 372 21687 0.09 0.001 7672 316 21653 0.083 0.001 6856 264 20969 0.086 0.001 5671
Heart - Left Ventricle 386 19884 0.083 0.001 6751 327 19820 0.076 0.001 5994 272 19335 0.082 0.001 5082
Kidney - Cortex 73 22404 0.083 0.001 1427 65 22592 0.076 0.001 1249 - - - - -
Liver 208 20765 0.076 0.001 4127 178 20529 0.077 0.001 3728 153 19988 0.078 0.001 2914
Lung 515 24687 0.079 0.001 9720 436 24434 0.078 0.001 8894 383 23646 0.081 0.001 7776
Minor Salivary Gland 144 23847 0.075 0.001 3454 114 23568 0.076 0.001 2858 85 22614 0.08 0.001 1822
Muscle - Skeletal 706 19978 0.076 0.001 9310 588 19893 0.075 0.001 8637 491 19407 0.076 0.001 7409
Nerve - Tibial 532 24512 0.111 0.001 12343 438 24349 0.11 0.001 11433 361 23487 0.112 0.001 9657
Ovary 167 23408 0.084 0.001 4123 138 23585 0.069 0.001 3240 122 22755 0.076 0.001 2809
Pancreas 305 21324 0.096 0.001 6945 243 21162 0.088 0.001 5863 220 20744 0.09 0.001 5094
Pituitary 237 25206 0.086 0.001 6490 219 25114 0.086 0.001 6283 157 23986 0.092 0.001 4402
Prostate 221 24749 0.075 0.001 5156 181 24421 0.075 0.001 4447 132 23879 0.066 0.001 2797
Skin - Not Sun Exposed (Suprapubic) 517 23977 0.091 0.001 10452 430 23817 0.091 0.001 9716 335 23081 0.086 0.001 7458
Skin - Sun Exposed (Lower leg) 605 23928 0.092 0.001 11486 508 23819 0.091 0.001 10814 414 23021 0.092 0.001 8879
Small Intestine - Terminal Ileum 174 23735 0.085 0.001 4270 141 24118 0.071 0.001 3482 122 23315 0.077 0.001 2879
Spleen 227 23925 0.106 0.001 7071 179 23595 0.107 0.001 6092 146 23085 0.096 0.001 4497
Stomach 324 22729 0.073 0.001 6127 260 22312 0.074 0.001 5306 237 21850 0.069 0.001 4456
Testis 322 32891 0.113 0.001 12724 272 32586 0.112 0.001 11565 225 31449 0.105 0.001 9253
Thyroid 574 24767 0.105 0.001 12253 482 24637 0.104 0.001 11496 399 23779 0.105 0.001 9826
Uterus 129 23440 0.07 0.001 2817 107 23145 0.07 0.001 2461 101 22515 0.074 0.001 2135
Vagina 141 23946 0.061 0.001 2715 120 23777 0.06 0.001 2331 106 23013 0.065 0.001 2013
Whole Blood 670 19196 0.081 0.001 8799 558 18989 0.08 0.001 8125 369 18440 0.084 0.001 6007

Table 2: Model performance in TWAS of height

Models built in GTEx v6, v7, and v8 were used to perform a TWAS of height from the UK BioBank (using summary statistics from Loh et al. 2018 Nat Genet). COLOC was used to evaluate colocalization statistics for genome-wide significant loci. Height was chosen as a highly heritable polygenic trait without extreme tissue specificity. Substantial increases in the number of TWAS associations and colocalized genes were observed from v6 to v7 (2.2x) and v7 to v8 (1.3x).

chisq: mean TWAS chi-squared statistic; hits: number of genome-wide significant genes; COLOC: number of genome-wide significant genes with posterior probability of colocalization (COLOC PP4) >0.8

  v6     v7     v8 (ALL)     v8 (EUR)    
  chisq hits COLOC chisq hits COLOC chisq hits COLOC chisq hits COLOC
AVERAGE 20.7 292 49.7 18.1 650.1 113.6 17.7 869.7 167.6 17.8 796.6 160.6
Adipose - Subcutaneous 22 546 100 18.3 1085 201 17.2 1381 263 17.3 1289 271
Adipose - Visceral (Omentum) 22.4 331 59 18.1 804 143 17.6 1087 189 17.9 989 188
Adrenal Gland 20 208 41 17.6 589 108 17.8 746 150 17.9 644 142
Artery - Aorta 20.6 485 95 18.1 899 180 18.3 1181 255 18.3 1099 256
Artery - Coronary 20.6 200 33 18.8 455 80 18.3 622 136 19.1 573 128
Artery - Tibial 21.7 594 112 18 1113 208 17.7 1381 258 18.1 1312 266
Brain - Amygdala       20.1 260 36 19.2 380 64 18.4 362 72
Brain - Anterior cingulate cortex (BA24)       19.2 345 50 17.2 469 85 17.3 435 83
Brain - Caudate (basal ganglia) 18.2 119 21 18.4 474 80 17.8 709 140 18.2 660 134
Brain - Cerebellar Hemisphere 19.9 226 35 17.1 565 112 16.7 845 186 17.2 799 176
Brain - Cerebellum 20.1 313 44 17.7 801 148 16.6 1004 226 16.9 961 207
Brain - Cortex 22.9 174 20 19.1 547 101 17.5 809 152 18 764 151
Brain - Frontal Cortex (BA9) 23 147 19 18.5 414 63 18.6 656 118 18.1 607 123
Brain - Hippocampus 22.3 95 6 19.3 314 45 18.3 519 108 18.3 470 91
Brain - Hypothalamus 22.2 86 9 18.1 306 44 19 553 93 19.5 524 85
Brain - Nucleus accumbens (basal ganglia) 20.2 130 12 16.1 393 57 18.1 719 136 17.8 637 128
Brain - Putamen (basal ganglia) 20 94 11 19.1 391 62 19.5 619 114 19.3 591 106
Brain - Spinal cord (cervical c-1)       19.2 279 29 17.1 453 73 17.1 420 67
Brain - Substantia nigra       20.1 234 18 18.4 361 62 17.8 305 49
Breast - Mammary Tissue 20.7 293 58 18.8 696 126 17.7 989 200 17.6 890 184
Skin - Transformed fibroblasts 19.4 612 115 17.7 954 187 18 1349 274 18.3 1282 280
Blood - EBV-transformed lymphocytes 22.9 236 40 18.9 380 69 17.9 466 88 18.6 385 76
Colon - Sigmoid 20.5 229 37 17.9 661 132 17.8 952 187 18.8 889 178
Colon - Transverse 21.9 333 70 17.6 719 135 17.1 1014 208 17.6 889 197
Esophagus - Gastroesophageal Junction 20 231 44 19.1 702 136 17.5 996 218 18.3 937 211
Esophagus - Mucosa 20.7 490 87 17.8 1037 185 17.3 1248 229 17.2 1153 222
Esophagus - Muscularis 20.7 535 108 18.2 1076 202 18 1294 283 17.9 1183 254
Heart - Atrial Appendage 21.4 270 42 18.6 784 136 18.1 979 206 18.4 929 190
Heart - Left Ventricle 17.7 227 43 17.6 667 138 17.3 844 169 16.8 760 166
Kidney - Cortex             18 191 16 17.7 165 19
Liver 18.9 108 18 18.7 408 73 17.3 559 115 17.2 498 115
Lung 20.5 452 73 17 963 170 17 1215 238 17.1 1112 221
Minor Salivary Gland       19.3 264 35 17.9 455 77 18.2 391 73
Muscle - Skeletal 20.6 436 67 18.4 984 175 17.8 1231 236 18.3 1150 219
Nerve - Tibial 20.7 633 117 17.8 1253 218 17.4 1574 292 17.4 1450 289
Ovary 22.3 157 24 18.5 397 52 19.1 608 113 18 433 91
Pancreas 21.3 260 44 17.6 678 102 17.1 901 176 17.5 782 149
Pituitary 21.9 176 32 19.2 595 105 17.3 820 145 17.3 802 147
Prostate 19.8 127 20 17.7 384 54 17.3 651 137 18.1 606 120
Skin - Not Sun Exposed (Suprapubic) 19.7 357 57 17.8 973 174 16.6 1278 222 17.2 1218 226
Skin - Sun Exposed (Lower leg) 20.6 584 107 16.6 1109 195 16.4 1366 270 16.5 1333 262
Small Intestine - Terminal Ileum 24.6 69 10 18.7 393 65 17.9 571 114 17.7 469 108
Spleen 21 210 25 17 567 90 16.6 920 161 17.1 799 182
Stomach 22.2 216 36 18.5 604 103 17.8 783 144 18.2 679 140
Testis 20.9 497 78 15.3 1073 175 15.1 1428 265 15.2 1305 258
Thyroid 19.7 602 99 17 1265 222 16.7 1516 275 16.9 1425 260
Uterus 17.8 82 11 17.9 291 45 18.7 418 66 18.2 350 58
Vagina 17.5 94 13 17 250 42 18.5 379 67 17.7 312 67
Whole Blood 20 290 47 17.7 808 147 17 1127 211 17.2 1016 184