Table 2.
Association of brain TL with clinical and neuropathologic phenotypes adjusting for cell composition from RNAseq data in N = 256 DLPFC brain samples and joint analysis evaluating the association of mtDNAcn, Cortical age and TL with outcomes adjusting for neuronal proportions from methylation data in N = 258 DLPFC brain samples.
| Phenotype | Modeling brain TL alone | Joint analysis of mtDNAcn, cortical clock, and brain TL | ||||||
|---|---|---|---|---|---|---|---|---|
| Effect TL | P TL | Effect mtDNAcn | P mtDNAcn | Effect clock | P clock | Effect TL | P TL | |
| Dementia diagnosis | 0.94 | 0.6077 | 0.61 | 0.0008 | 1.06 | 0.2468 | 1.06 | 0.6780 |
| Cognitive Impairment diagnosis | 0.89 | 0.3948 | 0.69 | 0.0318 | 1.04 | 0.5315 | 0.96 | 0.7997 |
| Global cognition* | 0.00 | 0.9677 | 0.32 | 1.7E−05 | − 0.06 | 0.0134 | − 0.06 | 0.3946 |
| Cognitive decline* | 0.00 | 0.8450 | 0.03 | 1.8E−05 | 0.00 | 0.0676 | 0.00 | 0.5286 |
| NIA-Reagan diagnosis | 0.97 | 0.7944 | 0.79 | 0.1584 | 1.19 | 0.0029 | 1.12 | 0.4652 |
| Global AD pathology* | 0.00 | 0.9922 | − 0.07 | 0.0034 | 0.03 | 0.0003 | 0.03 | 0.2242 |
| Amyloid* | − 0.15 | 0.0232 | − 0.05 | 0.4450 | 0.06 | 0.0047 | 0.11 | 0.0910 |
| Tau* | 0.04 | 0.5576 | − 0.30 | 0.0007 | 0.07 | 0.0183 | 0.10 | 0.2711 |
| TDP-43 | 0.89 | 0.2771 | 0.92 | 0.5433 | 1.03 | 0.5170 | 1.07 | 0.6056 |
| Lewy bodies | 0.88 | 0.3745 | 0.88 | 0.4216 | 1.16 | 0.0063 | 1.02 | 0.9001 |
| Hippocampal sclerosis | 0.56 | 0.0015 | 1.67 | 0.0298 | 1.08 | 0.3035 | 1.03 | 0.9133 |
| Gross chronic infarcts | 0.88 | 0.2655 | 0.75 | 0.0374 | 1.04 | 0.4195 | 0.98 | 0.8591 |
| Microinfarcts | 0.83 | 0.1443 | 0.84 | 0.2445 | 1.06 | 0.2829 | 1.03 | 0.8388 |
| Cerebral amyloid angiopathy | 1.08 | 0.4459 | 0.78 | 0.0449 | 1.02 | 0.5810 | 1.03 | 0.8204 |
| Cerebral atherosclerosis | 1.44 | 0.0007 | 0.81 | 0.0900 | 0.94 | 0.1565 | 1.10 | 0.4244 |
| Arteriolsclerosis | 0.95 | 0.6200 | 0.81 | 0.0867 | 0.94 | 0.1327 | 0.88 | 0.2632 |
Effect sizes are presented as Odds Ratios for categorical traits. For quantitative traits (indicated by *) the effect size is the β coefficient.
Each outcome was analyzed separately in a regression model adjusted for age, sex, and neuronal fraction from either RNA seq data (Modeling brain TL alone) or methylation data (Joint analysis of mtDNAcn, cortical clock, and brain TL). Clinical dementia diagnosis, MCI diagnosis, global cognition, and cognitive decline were adjusted for age, sex, neuronal fraction, and years of education. The beta values represent the change in pathologic outcomes for every 1 unit increase in TL, mtDNAcn, or Cortical clock age. The odds represent the increase or decrease in odds of moving into a higher group relative to baseline for every 1 unit increase in TL, mtDNAcn, or Cortical clock age. Associations between outcomes and mtDNAcn and Cortical clock age have been published previously in ROSMAP data34,36.
Significant values are in bold.