Multi-Omics Bioinformatic Analyses Linking LOXL4 with Spondylolisthesis.

Area of Science:

• Genetics
• Molecular Biology
• Bioinformatics

Background:

• Spondylolisthesis is a spinal disorder involving vertebral displacement, with its genetic underpinnings requiring further elucidation.
• Understanding the genetic factors is crucial for developing effective therapeutic strategies for spondylolisthesis.

Purpose of the Study:

• To identify key genes influencing the progression of spondylolisthesis.
• To investigate the causal genetic associations between gene expression and methylation with spondylolisthesis.

Main Methods:

• Summary-data-based Mendelian randomization (SMR) analysis was employed to assess eQTL and mQTL data.
• Bayesian colocalization analysis identified candidate genes, followed by qRT-PCR validation.
• Enrichment analysis, compound prediction, and molecular docking explored gene function and interactions.

Main Results:

• SMR analysis revealed numerous cis-eQTLs and mQTLs associated with spondylolisthesis.
• LOXL4 was identified as a key gene through Bayesian colocalization, showing strong eQTL and mQTL signals.
• LOXL4 is linked to extracellular matrix integrity and potentially regulated by hormones like estradiol and progesterone.

Conclusions:

• LOXL4 is proposed as a candidate gene involved in spondylolisthesis progression.
• LOXL4 represents a potential therapeutic target for spondylolisthesis.
• Further experimental validation is necessary to confirm the role of LOXL4 in spondylolisthesis.