TWAS / FUSION

GTEx v6 vs v7

Table 1: Model heritability

Heritability estimates across all genes in each tissue study from GTEx v6 and 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.

  v6         v7        
  N tot hsq hsq (se) hsq P<0.01 N tot hsq hsq (se) hsq P<0.01
AVERAGE 162 15039 0.077 0.002 1945 214 22232 0.086 0.001 4909
Adipose - Subcutaneous 298 15902 0.073 0.001 3579 385 22570 0.090 0.001 8193
Adipose - Visceral (Omentum) 185 15501 0.067 0.001 2100 313 22410 0.077 0.001 6174
Adrenal Gland 126 15355 0.072 0.001 1514 175 21608 0.094 0.001 4521
Artery - Aorta 197 15276 0.089 0.001 3047 267 21651 0.094 0.001 6463
Artery - Coronary 118 15527 0.073 0.001 1231 152 21796 0.079 0.001 3248
Artery - Tibial 285 15557 0.081 0.001 3844 388 21238 0.097 0.001 8224
Brain - Amygdala - - - - - 88 21523 0.076 0.001 1837
Brain - Anterior cingulate cortex (BA24) - - - - - 109 21714 0.082 0.001 2710
Brain - Caudate (basal ganglia) 100 14767 0.072 0.002 970 144 22461 0.081 0.001 3661
Brain - Cerebellar Hemisphere 89 14580 0.114 0.002 1542 125 22763 0.109 0.001 4408
Brain - Cerebellum 103 14925 0.111 0.002 2033 154 22835 0.128 0.001 5855
Brain - Cortex 96 14566 0.085 0.002 1069 136 22426 0.094 0.001 4012
Brain - Frontal Cortex (BA9) 92 14549 0.072 0.002 950 118 22303 0.086 0.001 3144
Brain - Hippocampus 81 14526 0.063 0.003 558 111 21685 0.073 0.001 2295
Brain - Hypothalamus 81 14802 0.059 0.002 619 108 22590 0.069 0.001 2315
Brain - Nucleus accumbens (basal ganglia) 93 14730 0.074 0.002 906 130 22688 0.080 0.001 3240
Brain - Putamen (basal ganglia) 82 14212 0.067 0.002 647 111 21489 0.087 0.001 2818
Brain - Spinal cord (cervical c-1) - - - - - 83 22112 0.085 0.001 2006
Brain - Substantia nigra - - - - - 80 21390 0.079 0.001 1604
Breast - Mammary Tissue 183 15814 0.066 0.001 2041 251 22987 0.075 0.001 5044
Blood - EBV-transformed lymphocytes 114 14072 0.094 0.001 1464 117 20692 0.084 0.001 2758
Skin - Transformed fibroblasts 272 14659 0.098 0.001 4288 300 20086 0.109 0.001 7353
Colon - Sigmoid 124 15518 0.070 0.001 1528 203 22114 0.084 0.001 4874
Colon - Transverse 169 15467 0.076 0.001 2133 246 22709 0.076 0.001 5316
Esophagus - Gastroesophageal Junction 127 15519 0.068 0.001 1500 213 21542 0.084 0.001 4888
Esophagus - Mucosa 241 15380 0.080 0.001 3391 358 21741 0.098 0.001 8061
Esophagus - Muscularis 218 15505 0.085 0.001 3316 335 21673 0.096 0.001 7773
Heart - Atrial Appendage 159 14703 0.072 0.001 1634 264 20969 0.086 0.001 5671
Heart - Left Ventricle 190 14613 0.059 0.001 1581 272 19335 0.082 0.001 5082
Liver 97 14113 0.061 0.003 756 153 19988 0.078 0.001 2914
Lung 278 16014 0.064 0.001 2938 383 23646 0.081 0.001 7776
Minor Salivary Gland - - - - - 85 22614 0.080 0.001 1822
Muscle - Skeletal 361 14750 0.054 0.001 2976 491 19407 0.076 0.001 7409
Nerve - Tibial 256 15914 0.105 0.001 4424 361 23487 0.112 0.001 9657
Ovary 85 15423 0.081 0.002 948 122 22755 0.076 0.001 2809
Pancreas 149 14010 0.082 0.001 1691 220 20744 0.090 0.001 5094
Pituitary 87 15444 0.045 0.046 1165 157 23986 0.092 0.001 4402
Prostate 87 15741 0.077 0.002 880 132 23879 0.066 0.001 2797
Skin - Not Sun Exposed (Suprapubic) 196 15436 0.079 0.001 2548 335 23081 0.086 0.001 7458
Skin - Sun Exposed (Lower leg) 302 15775 0.076 0.001 3729 414 23021 0.092 0.001 8879
Small Intestine - Terminal Ileum 77 11126 0.082 0.002 491 122 23315 0.077 0.001 2879
Spleen 89 15102 0.112 0.002 1463 146 23085 0.096 0.001 4497
Stomach 170 15439 0.060 0.001 1507 237 21850 0.069 0.001 4456
Testis 157 15467 0.118 0.001 3222 225 31449 0.105 0.001 9253
Thyroid 278 16119 0.087 0.001 4082 399 23779 0.105 0.001 9826
Uterus 70 15255 0.081 0.002 608 101 22515 0.074 0.001 2135
Vagina 79 15473 0.073 0.002 675 106 23013 0.065 0.001 2013
Whole Blood 338 14033 0.043 0.001 2058 369 18440 0.084 0.001 6007

Table 2: Model performance in TWAS of height

Models built in GTEx v6 and v7 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. The average association statistic did not change substantially from v6 to v7 but the average number of significant TWAS associations and colocalized genes increased by 2.1x. Tissues that saw the largest increase in associations were: small intestine, liver, and uterus.

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    
  chisq hits COLOC chisq hits COLOC
AVERAGE 22.2 294 63 22.8 630 126
Adipose - Subcutaneous 23.0 549 115 23.3 973 207
Adipose - Visceral (Omentum) 23.7 335 71 24.9 718 144
Adrenal Gland 20.1 209 48 20.0 521 114
Artery - Aorta 21.8 488 104 22.0 818 183
Artery - Coronary 20.8 198 40 22.2 402 88
Artery - Tibial 21.8 604 140 21.8 1001 198
Brain - Amygdala         250 49
Brain - Anterior cingulate cortex (BA24)         311 59
Brain - Caudate (basal ganglia) 20.8 122 26 22.8 425 82
Brain - Cerebellar Hemisphere 20.9 224 53 21.5 517 113
Brain - Cerebellum 21.3 313 69 22.1 756 147
Brain - Cortex 23.2 174 30 23.3 515 99
Brain - Frontal Cortex (BA9) 26.5 146 25 27.1 378 72
Brain - Hippocampus 24.1 101 9 25.1 290 50
Brain - Hypothalamus 25.6 88 15 25.8 291 51
Brain - Nucleus accumbens (basal ganglia) 25.1 135 24 21.8 355 64
Brain - Putamen (basal ganglia) 23.3 97 17 23.1 351 74
Brain - Spinal cord (cervical c-1)         287 46
Brain - Substantia nigra         240 27
Breast - Mammary Tissue 21.1 307 72 22.7 694 143
Blood - EBV-transformed lymphocytes 23.5 241 48 22.8 384 78
Skin - Transformed fibroblasts 20.0 608 140 20.0 950 201
Colon - Sigmoid 21.4 225 55 22.0 657 142
Colon - Transverse 23.1 337 81 24.3 729 145
Esophagus - Gastroesophageal Junction 20.8 228 57 21.2 706 155
Esophagus - Mucosa 21.9 495 108 21.7 1022 206
Esophagus - Muscularis 21.4 534 132 22.1 1054 214
Heart - Atrial Appendage 22.0 275 59 23.4 775 168
Heart - Left Ventricle 19.2 233 51 20.7 673 152
Liver 20.4 106 23 19.8 407 87
Lung 21.2 460 99 21.9 960 191
Minor Salivary Gland         268 40
Muscle - Skeletal 22.0 434 81 22.4 971 189
Nerve - Tibial 21.7 639 142 21.5 1239 246
Ovary 25.6 158 33 26.4 394 66
Pancreas 21.8 271 57 21.4 666 114
Pituitary 24.0 177 42 24.6 598 118
Prostate 23.5 130 21 24.0 374 62
Skin - Not Sun Exposed (Suprapubic) 20.8 362 77 21.2 974 195
Skin - Sun Exposed (Lower leg) 21.3 585 122 21.3 1086 215
Small Intestine - Terminal Ileum 28.7 75 17 30.7 401 90
Spleen 22.0 211 35 23.3 567 108
Stomach 22.5 216 47 23.5 599 123
Testis 22.2 491 98 22.7 1063 199
Thyroid 20.0 603 129 21.2 1264 252
Uterus 20.4 79 15 21.6 297 58
Vagina 20.1 91 16 22.8 254 50
Whole Blood 20.4 289 58 20.8 796 166