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

Area of Science:

• Neuroscience
• Metabolic Disorders
• Genetics
• Bioinformatics

Background:

• Alzheimer's disease (AD) is a neurodegenerative disorder, while type 2 diabetes mellitus (T2DM) is a metabolic disorder.
• Genetic studies increasingly suggest a link between AD and T2DM, but underlying mechanisms remain unclear.
• Current association analyses have limited power to elucidate shared disease pathways.

Purpose of the Study:

• To develop and apply novel causal inference methods for genetic studies of AD and T2DM.
• To systematically analyze multi-omic data to infer causal networks.
• To discover common genetic and molecular pathways shared by AD and T2DM.

Main Methods:

• Development of novel causal inference methods for genetic studies.
• Implementation of systematic multi-omic causal analysis pipelines.
• Application of pipelines to genetic and omics data from 448 individuals in the ROSMAP Project.

Main Results:

• Identification of 13 shared causal genes between AD and T2DM.
• Discovery of 16 shared causal pathways connecting AD and T2DM.
• Construction of multi-omics causal networks revealing 754 gene expression and 101 gene methylation nodes linked to both diseases.

Conclusions:

• Novel causal inference methods effectively identified shared genetic and molecular pathways between AD and T2DM.
• The findings provide a deeper understanding of the common biological mechanisms underlying these distinct diseases.
• This research opens new avenues for therapeutic strategies targeting shared pathways.