Laying a solid foundation for Manhattan--'setting the functional basis for the post-GWAS era'.

Area of Science:

• Genetics
• Genomics
• Molecular Biology

Background:

• Genome-wide association studies (GWAS) have identified numerous genetic variants, primarily single-nucleotide polymorphisms (SNPs), linked to human traits and diseases.
• While coding variants' functional impact is often clear, most disease-associated variants reside in non-coding regions, posing interpretation challenges.

Purpose of the Study:

• To review recent advancements in annotating non-coding genomic regions.
• To discuss how these annotations aid in identifying functional targets of GWAS risk loci.
• To explore the implications for interpreting disease-associated mutations from whole-genome sequencing.

Main Methods:

• Review of current literature on non-coding genome annotation and its application in post-GWAS analysis.
• Analysis of how genetic variants modulate cis-regulatory elements to affect gene expression.
• Integration of findings with the interpretation of whole-genome sequencing data for disease mutations.

Main Results:

• Non-coding variants, particularly those affecting cis-regulatory elements, are crucial for understanding gene expression changes.
• Genome annotation facilitates the functional characterization of risk-associated loci identified by GWAS.
• These findings are vital for interpreting disease-associated mutations found through whole-genome sequencing.

Conclusions:

• Understanding non-coding variants is essential for advancing the post-GWAS era.
• Functional annotation of the non-coding genome is critical for disease gene discovery and interpretation.
• This knowledge bridges the gap between genetic associations and biological mechanisms underlying disease.