Shared Causal Paths underlying Alzheimer’s dementia and Type 2 Diabetes

Although Alzheimer’s disease (AD) is a central nervous system disease and type 2 diabetes MELLITUS (T2DM) is a metabolic disorder, an increasing number of genetic epidemiological studies show clear link between AD and T2DM. The current approach to uncovering the shared pathways between AD and T2DM involves association analysis; however such analyses lack power to discover the mechanisms of the diseases. As an alternative, we developed novel causal inference methods for genetic studies of AD and T2DM and pipelines for systematic multi-omic casual analysis to infer multilevel omics causal networks for the discovery of common paths from genetic variants to AD and T2DM. The proposed pipelines were applied to 448 individuals from the ROSMAP Project. We identified 13 shared causal genes, 16 shared causal pathways between AD and T2DM, and 754 gene expression and 101 gene methylation nodes that were connected to both AD and T2DM in multi-omics causal networks.