Genome-wide meta-analysis identifies genetic locus on chromosome 9 associated with Modic changes

Area of Science:

• Genetics
• Orthopedics
• Radiology

Background:

• Low back pain (LBP) is a prevalent disabling condition.
• Lumbar disc degeneration (LDD) is a potential contributor to LBP.
• Modic Changes (MC), a phenotype of LDD, are MRI-detected bone marrow signal alterations strongly associated with LBP and approximately 30% heritable.

Purpose of the Study:

• To identify genetic loci associated with Modic Changes (MC) using a genome-wide meta-analysis.

Main Methods:

• MC presence was assessed via lumbar MRI in the Northern Finland Birth Cohort 1966 (n=1182) and TwinsUK (n=647).
• Genome-wide association analyses were performed using linear regression.
• A meta-analysis was conducted using the inverse-variance weighting approach.

Main Results:

• A significant locus (p<5e-8) associated with MC was identified on chromosome 9, with rs1934268 in the PTPRD gene as the lead single nucleotide polymorphism (SNP).
• This SNP is located within a binding region for BCL11A, SPI1, and PBX3 transcription factors.
• Suggestive signals (p<1e-5) were also found near XKR4, SCIN, MGMT, DLG2, ZNF184, and OPRK1.

Conclusions:

• PTPRD emerges as a novel candidate gene for MC, potentially influencing cartilage or nervous system development.
• Further research is required to elucidate the precise mechanisms linking PTPRD to MC development.
• This genome-wide meta-analysis provides a foundation for future studies investigating the genetic factors contributing to spine degeneration and LBP.