Genetic study of complex diseases in the post-GWAS era

Area of Science:

• Genetics
• Genomics
• Bioinformatics

Background:

• Genome-wide association studies (GWASs) have identified thousands of genetic variants, primarily single nucleotide polymorphisms (SNPs), associated with complex human diseases.
• Understanding the functional consequences and mechanisms of these identified SNPs and genes is a critical challenge in disease research.

Purpose of the Study:

• To review recent advancements in understanding the functional impacts of GWAS-associated non-coding regulatory SNPs.
• To discuss the utility of systems genetics and network biology approaches for interpreting GWAS findings.

Main Methods:

• Literature review of functional characterization studies for GWAS-identified SNPs.
• Discussion of systems genetics and network biology methodologies.

Main Results:

• SNPs in protein-coding genes can alter amino acids, significantly impacting protein function and disease pathogenesis.
• Regulatory SNPs exert complex effects on gene expression via mechanisms including RNA splicing, transcription factor binding, DNA methylation, and miRNA recruitment.

Conclusions:

• Functional elucidation of non-coding regulatory SNPs is essential for understanding complex disease mechanisms.
• Systems genetics and network biology offer powerful frameworks for interpreting large-scale GWAS data and uncovering gene function.