[Fine mapping of complex disease susceptibility loci]

Area of Science:

• Genetics
• Genomics
• Molecular Biology

Context:

• Genome-wide association studies (GWAS) have identified over 3800 loci linked to diseases and traits.
• Significant challenges remain in identifying specific causative variants and their biological functions within these loci.
• Clarifying these variants is essential for understanding disease pathogenesis and discovering novel biomarkers.

Purpose:

• To review and summarize current strategies and challenges in fine-mapping genetic loci identified by GWAS.
• To highlight methods for identifying causative variants and susceptibility genes.
• To discuss approaches for elucidating the functional roles of genetic variants in complex diseases.

Summary:

• Fine-mapping strategies are crucial in the post-GWAS era to identify causative variants and susceptibility genes.
• Techniques include imputation, re-sequencing, expression quantitative trait locus (eQTL) analysis, and haplotype analysis for common variants.
• For rare variants, methods like family-based analysis and burden tests are employed.

Impact:

• Enables a deeper understanding of the biological mechanisms underlying complex diseases.
• Facilitates the discovery of new diagnostic biomarkers and therapeutic targets.
• Advances precision medicine by linking specific genetic variations to disease risk and function.