• Bo-Wen Ren, Yi-Hao Liu, Jian-Hui Wu, Bo-Chen An, Qing-Zu Liu, Chong-Yang Liu, Ke-Ya Mao, and Jian-Heng Liu.
• Department of Orthopedics, Chinese PLA General Hospital, Beijing, 100853, China.
• Eur Spine J. 2024 Nov 6.

PurposeIntervertebral disc degeneration (IVDD) considerably impacts global disability and quality of life. Although potential links between plasma proteins and IVDD exist, their causal correlation remains undefined. This study explored the causal links between plasma proteins and IVDD employing genome-wide association study data.MethodsFor this observational study, summary statistics for plasma proteins were derived from an Icelandic population, paralleled with genome-wide data on IVDD obtained from the FinnGen consortium. Using two-sample Mendelian randomization, we assessed the causal relationship between 4,907 plasma proteins and IVDD. Standard sensitivity analyses encompassing heterogeneity, pleiotropy, and leave-one-out cross-validation tests confirmed the stability and robustness of the findings. Subsequently, through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein interaction analyses, we delved into the functional interrelation among identified plasma proteins.ResultsA causal association with IVDD was identified for 47 plasma proteins; myoneurin, intersectin 1, and eukaryotic translation initiation factor 4 gamma 3 maintained significant correlations post multiple correction tests (P < 1.02 × 10- 5), influencing IVDD development positively. GO/KEGG pathway analyses confirmed that multiple pathways may be involved in IVDD development.ConclusionThe study underscores the causal correlation between plasma protein levels and IVDD risk. These identified proteins could emerge as unique biomarkers for IVDD, contributing to its predictive measures. The findings further our understanding of IVDD pathomechanisms and prospective therapeutic targets.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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