Table 1.
CONTENT outperforms existing methods in TWAS across 22 complex traits and diseases
| GTEx | CLUES | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Trait | Context-by-context | UTMOST | CONTENT (All) | CONTENT (Full) | CONTENT (Specific) | CONTENT (Shared) | Context-by- context | UTMOST | CONTENT (All) | CONTENT (Full) | CONTENT (Specific) | CONTENT (Shared) |
| AD | 17 | 9 | 24 | 20 | 20 | 11 | 7 | 5 | 15 | 9 | 13 | 3 |
| Asthma | 155 | 90 | 237 | 181 | 195 | 67 | 74 | 63 | 127 | 101 | 104 | 34 |
| Bipolar | 42 | 45 | 83 | 63 | 65 | 39 | 9 | 14 | 35 | 20 | 25 | 5 |
| CAD | 10 | 11 | 23 | 18 | 15 | 8 | 6 | 6 | 10 | 7 | 6 | 0 |
| CKD | 26 | 19 | 42 | 31 | 32 | 18 | 2 | 4 | 6 | 5 | 5 | 1 |
| Crohn’s | 77 | 63 | 95 | 73 | 83 | 47 | 27 | 22 | 44 | 30 | 37 | 9 |
| Eczema | 32 | 13 | 57 | 44 | 41 | 10 | 8 | 5 | 11 | 9 | 9 | 3 |
| FastGlu | 16 | 8 | 19 | 12 | 14 | 7 | 3 | 3 | 6 | 6 | 6 | 0 |
| HDL | 58 | 29 | 79 | 60 | 73 | 36 | 21 | 14 | 28 | 23 | 25 | 6 |
| IBS | 9 | 5 | 25 | 20 | 16 | 3 | 3 | 1 | 7 | 5 | 6 | 1 |
| LDL | 89 | 57 | 132 | 107 | 116 | 58 | 47 | 29 | 51 | 40 | 44 | 14 |
| Lupus | 93 | 54 | 129 | 94 | 104 | 51 | 36 | 27 | 58 | 42 | 48 | 11 |
| MDD | 99 | 79 | 169 | 132 | 134 | 62 | 20 | 29 | 47 | 32 | 39 | 3 |
| MS | 20 | 10 | 42 | 32 | 25 | 9 | 9 | 7 | 11 | 8 | 10 | 5 |
| PBC | 62 | 42 | 65 | 55 | 58 | 33 | 21 | 14 | 30 | 24 | 26 | 6 |
| Psoriasis | 47 | 22 | 58 | 46 | 41 | 16 | 13 | 10 | 21 | 17 | 16 | 6 |
| RA | 73 | 56 | 99 | 79 | 86 | 46 | 40 | 20 | 51 | 33 | 45 | 9 |
| Sarcoidosis | 19 | 13 | 30 | 27 | 26 | 8 | 6 | 4 | 6 | 6 | 4 | 2 |
| Sjogren | 17 | 9 | 31 | 25 | 21 | 6 | 4 | 2 | 7 | 6 | 6 | 1 |
| T1D | 77 | 64 | 109 | 88 | 84 | 49 | 26 | 23 | 41 | 36 | 29 | 13 |
| T2D | 193 | 115 | 246 | 208 | 205 | 112 | 76 | 76 | 112 | 77 | 98 | 17 |
| Ulc colitis | 16 | 10 | 40 | 30 | 26 | 7 | 5 | 4 | 11 | 9 | 7 | 2 |
TWAS results (unique loci, merging genes within 1MB) across 22 complex traits and diseases using weights output by CONTENT, UTMOST, and the context-by-context method. CONTENT(All) refers to the collection of all loci output by at least one CONTENT model. CONTENT(Full) added an average of 15% and 19% of gene-trait discoveries over the CONTENT(Shared) and CONTENT(Specific) approaches together at an hFDR of 5% in GTEx and CLUES respectively.
Numbers in bold font indicate the method with the greatest number of discoveries. AD Alzheimer’s disease, CAD Coronary Artery Disease, CKD Chronic Kidney Disease, Crohn’s Crohn’s Disease, FastGlu Fasting Glucose, GFR Glomerular filtration rate, HDL High-density lipoprotein, IBS Irritable bowel syndrome, LDL Low-density lipoprotein, Lupus Systemic lupus erythematosus, MDD Major depressive disorder, MS Multiple sclerosis, PBC Primary biliary cholangitis, RA Rheumatoid arthritis, Sjogren Sjögren’s syndrome, T1D Type 1 diabetes, T2D Type 2 diabetes, TG Triglycerides, Ulc colitis Ulcerative colitis.
See Supplementary Table 2 for GWAS trait information