Table 4.
Mendelian randomization analysis and replication results
| Exposure | Outcome | MR analysis | Replication | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| N SNPs | Beta | SE | P value | FDR | N SNPs | Beta | SE | p value | ||
| Case–control GWAS | Alanine aminotransferase | 20 | − 0.024 | 0.012 | 0.041 | 0.057 | ||||
| Alkaline phosphatase | 20 | − 0.030 | 0.012 | 0.015 | 0.032*a | |||||
| Apolipoprotein A | 20 | − 0.068 | 0.021 | 0.012 | 0.032* | 20 | − 0.003 | 0.022 | 0.895 | |
| Apolipoprotein B | 19 | 0.126 | 0.054 | 0.019 | 0.032* | 20 | 0.064 | 0.091 | 0.483 | |
| Cholesterol | 20 | 0.082 | 0.035 | 0.019 | 0.032* | 20 | 0.096 | 0.035 | 0.006* | |
| C-reactive protein | 20 | − 0.192 | 0.064 | 0.003 | 0.032* | 20 | − 0.181 | 0.077 | 0.018* | |
| Gamma glutamyltransferase | 20 | − 0.008 | 0.008 | 0.341 | 0.38 | |||||
| Haematocrit percentage | 20 | − 0.008 | 0.008 | 0.341 | 0.39 | |||||
| Haemoglobin concentration | 20 | − 0.001 | 0.004 | 0.803 | 0.803 | |||||
| HDL cholesterol | 20 | − 0.028 | 0.014 | 0.043 | 0.050 | |||||
| LDL direct | 20 | 0.095 | 0.041 | 0.020 | 0.032* | 20 | 0.093 | 0.040 | 0.020* | |
| Monocyte count | 20 | − 0.006 | 0.008 | 0.475 | 0.50 | |||||
| Platelet count | 20 | − 0.020 | 0.008 | 0.014 | 0.032* | 20 | − 0.041 | 0.025 | 0.094 | |
| Platelet crit | 20 | − 0.025 | 0.010 | 0.014 | 0.032* | 20 | − 0.054 | 0.018 | 0.003* | |
| Red blood cell (erythrocyte) count | 20 | − 0.014 | 0.005 | 0.007 | 0.032* | 20 | − 0.004 | 0.019 | 0.845 | |
| Red blood cell (erythrocyte) distribution width | 20 | − 0.037 | 0.013 | 0.004 | 0.032* | 20 | − 0.041 | 0.015 | 0.007* | |
| Braak stage GWAS | Apolipoprotein A | 25 | − 0.061 | 0.024 | 0.012 | 0.020* | 26 | − 0.063 | 0.022 | 0.004* |
| Apolipoprotein B | 24 | 0.005 | 0.005 | 0.324 | 0.320 | |||||
| Cholesterol | 24 | 0.007 | 0.006 | 0.256 | 0.320 | |||||
| C-reactive protein | 25 | − 0.176 | 0.058 | 0.002 | 0.008* | 25 | − 0.087 | 0.069 | 0.210 | |
| LDL direct | 26 | 26.000 | 0.126 | 0.003 | 0.008* | 26 | 0.133 | 0.042 | 0.002* | |
The table presents the results of a Mendelian Randomization (MR) analysis and subsequent replication studies investigating the causal relationships between genetic risk factors (exposures) from ncAD and Braak stage GWAS and various blood biomarkers (outcomes) identified from previous PheWAS analysis. Exposure: Either ncAD GWAS or Braak stage GWAS, representing the genetic risk factors being tested. Outcome: The specific blood biomarkers identified through PheWAS analysis, which are the traits being evaluated for causal relationships with the genetic exposures. Replication: Results from replication studies, including the number of SNPs (N SNPs), beta coefficient, standard error (SE), and p-value for select outcomes that were re-tested to confirm consistency in the results. This table focuses on the primary inverse variance-weighted (IVW) analysis, with additional methods and sensitivity tests available in Supplementary Table 8. An asterisk (*) indicates a significant cutoff; The letter "a" indicates that the replicate dataset is not available