Table 5. Results of conditional regression analyses.
For each regression equation, dependent variables are listed in the top row, independent variables in the second row. For conditional regressions (two columns to the far right) the dependent variables were the residuals from an initial regression and the independent variables were the genotypes of candidate SNPs. [Protein~Disease status] indicates that protein concentration was the dependent variable and disease status was the independent variable in the initial regression. Similarly, [Disease status~ Protein] indicates that disease status was the dependent variable and protein concentration was the independent variable in the initial regression. Correlation statistics indicating the amount of variance explained by the independent variable is presented where appropriate for each regression. Results of regression analyses recapitulated the GWAS results for F7, MCP-1 and adiponectin (column one). In addition, there were significant associations between AD status and blood concentrations of F7, MCP-1 and adiponectin (column two). Conditional regression analyses suggested that candidate SNPs contributed to variation in protein concentration independent of AD status (column three). None of the results of regressions interrogating whether genotypes contributed directly to disease risk independent of protein endophenotype were significant (column four). However, due to insufficient statistical power, it was not possible to determine the true relationship between these factors.
| Dependent Variable | Protein concentration | Disease status | Residuals of Protein Concentration Regressed on Disease Status | Residuals of Disease Status Regressed on Protein Concentration | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Independent Variable | Genotype | Protein concentration | Genotype | Genotype | |||||||
| Cohort | Protein | Marker | Gene | p | r2 | p | r2 | p | r2 | p | r2 |
| TARCC | Adipo | chr3.186558403 | MAP3K13 | 6.31E-10 | 24% | 0.016 | NA | 0.001 | 4% | 0.574 | 0% |
| ADNI | Adipo | chr3.186558403 | MAP3K13 | 5.09E-05 | 31% | 0.023 | NA | 0.017 | 5% | 0.244 | 1% |
| TARCC | Adipo | rs8111139 | ZNF320 | 3.91E-10 | 22% | 0.026 | NA | 3.24E-04 | 4% | 0.208 | 1% |
| ADNI | Adipo | rs8111139 | ZNF320 | 3.58E-04 | 28% | 0.023 | NA | 0.982 | 0% | 0.653 | 0% |
| TARCC | F7 | rs561241 | F7 | 0.001 | 13% | 0.001 | NA | 0.011 | 2% | 0.386 | 0% |
| ADNI | F7 | rs561241 | F7 | 0.002 | 24% | 0.069 | NA | 0.006 | 6% | 0.998 | 0% |
| TARCC | MCP-1 | rs11663180 | ATP9B | 0.022 | 9% | 0.014 | NA | 3.03E-05 | 6% | 0.959 | 0% |
| ADNI | MCP-1 | rs11663180 | ATP9B | 0.010 | 21% | 0.092 | NA | 0.003 | 7% | 0.390 | 1% |
| TARCC | MCP-1 | rs35548358 | TREM1 | 0.759 | 3% | 0.009 | NA | 0.054 | 1% | 0.350 | 0% |
| ADNI | MCP-1 | rs35548358 | TREM1 | 0.031 | 19% | 0.092 | NA | 0.012 | 5% | 0.161 | 2% |