From GWASs toward Mechanistic Understanding with Case Studies in Dermatogenetics

Area of Science:

• Genetics
• Dermatology
• Computational Biology

Background:

• Human skin diseases arise from complex, often unknown, genetic and environmental interactions.
• Genome-Wide Association Studies (GWASs) identify genetic variants linked to complex diseases, but pinpointing causal genes and mechanisms remains challenging.
• Interpreting functional impacts of genetic variants is crucial for understanding disease etiology, diagnostics, and drug discovery.

Purpose of the Study:

• To provide a practical overview of methods and datasets for genetic variant interpretation.
• To highlight key aspects of variant interpretation: prioritizing causal genes, cell types, and pathways.
• To offer a blueprint for in silico genetic analysis using examples from atopic dermatitis research.

Main Methods:

• Review and synthesis of current computational methods and datasets for functional variant interpretation.
• Prioritization strategies for identifying causal genes, cell types, and biological pathways.
• Application of these strategies using case studies from atopic dermatitis genetic research.

Main Results:

• A structured approach to genetic variant interpretation is presented, focusing on three key areas.
• Examples from atopic dermatitis research demonstrate the practical application of the proposed framework.
• A curated list of resources, including tools and packages, is provided for researchers.

Conclusions:

• Effective interpretation of genetic variants requires prioritizing causal genes, cell types, and pathways.
• The presented framework and resources can guide researchers in conducting in silico follow-up analyses.
• This approach facilitates a deeper understanding of genetic contributions to skin diseases and aids in translational research.