Ankylosing spondylitis: beyond genome-wide association studies

Area of Science:

• Genetics
• Immunology
• Rheumatology

Background:

• Ankylosing spondylitis (AS) pathogenesis involves complex genetic, environmental, and immunological factors.
• Genome-wide association (GWA) studies identified key pathways like IL-23/IL-17 but explained only a fraction of heritability.

Purpose of the Study:

• To review genomic investigations in ankylosing spondylitis (AS) beyond traditional GWA studies.
• To summarize genetic variants with genome-wide significance and their role in disease pathogenesis.

Main Methods:

• Review of literature focusing on genomic investigations beyond GWA studies.
• Inclusion of copy number variants, gene expression profiling (including microRNA), epigenetics, rare variants, and gene-gene interactions.

Main Results:

• GWA studies highlighted immunomodulatory pathways, particularly the interleukin-23/interleukin-17 axis.
• A significant portion of AS heritability remains unexplained ('missing heritability').

Conclusions:

• Addressing 'missing heritability' requires rethinking study designs and implementing advanced technologies.
• Next-generation sequencing, epigenetics, miRNA technologies, and familial studies are crucial for future AS genomic discoveries.