Table 1.
Summary of the source GWAS and number of causal proteins for each brain trait identified through PWAS, SMR/HEIDI, and COLOC
| GWAS statistics | Causal protein counts | Causal proteins shared among traits | ||||||
|---|---|---|---|---|---|---|---|---|
| N | significant SNPs | cis | trans | total | Psychiatric | Neuro-degenerative | Brain structure | |
| Psychiatric | ||||||||
| Major depressive disorder | 807,553 | 9744 | 96 | 2 | 98 | 46% | 2% | 8% |
| Bipolar disorder | 51,710 | 240 | 70 | 0 | 70 | 44% | 3% | 7% |
| Schizophrenia | 77,096 | 14,724 | 156 | 2 | 158 | 31% | 3% | 7% |
| Anxiety | 175,163 | 166 | 4 | 0 | 4 | 75% | 50% | 25% |
| Post-traumatic stress disorder | 214,408 | 4607 | 16 | 0 | 16 | 44% | 6% | 13% |
| Alcoholism | 300,789 | 1857 | 19 | 1 | 20 | 45% | 10% | 5% |
| Neuroticism | 390,278 | 7759 | 122 | 2 | 124 | 34% | 4% | 6% |
| Insomnia | 386,533 | 463 | 29 | 0 | 29 | 41% | 0% | 10% |
| Neurodegenerative | ||||||||
| Alzheimer’s disease (AD1) | 455,258 | 2357 | 16 | 2 | 18 | 39% | 22% | 6% |
| Alzheimer’s disease (AD2) | 63,926 | 1506 | 3 | 1 | 4 | 50% | 50% | 0% |
| Frontotemporal dementia | 12,908 | 29 | 0 | 0 | 0 | – | – | – |
| Amyotrophic lateral sclerosis | 80,610 | 182 | 6 | 0 | 6 | 17% | 0% | 0% |
| Lewy body dementia | 6618 | 189 | 0 | 0 | 0 | – | – | – |
| Parkinson’s disease | 482,730 | 3464 | 19 | 1 | 20 | 25% | 10% | 15% |
| Brain structure | ||||||||
| Hippocampal volume | 26,814 | 461 | 2 | 0 | 2 | 0% | 0% | 50% |
| Nucleus accumbens volume | 32,562 | 138 | 3 | 0 | 3 | 0% | 0% | 0% |
| Amygdala volume | 34,431 | 0 | 0 | 0 | 0 | – | – | – |
| Putamen volume | 37,571 | 1465 | 6 | 0 | 6 | 50% | 17% | 50% |
| Brainstem volume | 28,809 | 1063 | 10 | 0 | 10 | 50% | 10% | 30% |
| Caudate nucleus volume | 37,741 | 141 | 7 | 0 | 7 | 14% | 0% | 29% |
| Globus pallidus volume | 34,413 | 272 | 7 | 0 | 7 | 14% | 14% | 43% |
| Thalamus volume | 34,464 | 50 | 2 | 0 | 2 | 50% | 0% | 50% |
| Cortical thickness | 33,992 | 370 | 19 | 0 | 19 | 37% | 5% | 21% |
| White matter hyperintensity | 48,454 | 1340 | 19 | 1 | 20 | 30% | 0% | 15% |
| Cortical surface area | 33,992 | 1127 | 20 | 0 | 20 | 40% | 15% | 15% |
The sample size (N) for each trait is the number of samples that contributed to the GWAS results used in our analysis, which may be smaller than the sample reported in the original GWAS publication due to data access limitations or restricting to samples of European ancestry. GWAS-significant SNPs were defined as SNPs with p value <5 × 10−8. A protein is considered shared with another trait group if it is also causal for any other trait in that group. Since different traits have different number of identified causal proteins, we examined the percentage of the causal proteins of each trait that is shared within a trait group or between two trait groups. This information is also depicted in Figs. 3A and 4A.