Analysis of 179 lipid traits reveals significant causal relationships with intervertebral disc degeneration (IVDD), lower back pain (LBP), and sciatica.
Glycerophospholipids, sterols, and glycerolipids are significantly associated with the risk of IVDD, LBP, and sciatica.
Phosphatidylcholine and triglycerides may increase the incidence of IVDD, LBP, and sciatica.
Sphingomyelin (d38:2) shows a protective effect against LBP.
Sterol esters demonstrate variable impacts on sciatica, with one specific sterol ester (27:1/16:1) consistently indicating a detrimental effect across all three conditions.
The study highlights the complex nature of lipid metabolism and its influence on these conditions.
Simplified
Degeneration of intervertebral discs is a significant factor in chronic lower back pain, impacting millions annually. Existing studies propose a potential link between lipids and disc disease, though causal relationships remain unclear. The objective of this study is to explore the causal connections between lipids, lower back pain, disc degeneration, and the risk of sciatica In this research, we utilized a comprehensive GWAS dataset encompassing 179 lipid traits to explore the causal connections between lipids and the susceptibility to conditions such as lower back pain (LBP), intervertebral disc degeneration (IVDD), and sciatica. To establish causality, we employed two-sample , supplemented by Bayesian model averaging for verification. Our assessment of diversity and mutual influence involved Cochran's Q test, MR-Egger intercept assessment, and MR-PRESSO. Additionally, we performed a sensitivity analysis by systematically excluding individual elements to gauge their impact on outcomes in Mendelian randomization. Lastly, bidirectional Mendelian randomization was conducted to explore potential inverse associations between lipids and IVDD. Analyzing 179 lipidomic features as exposures and IVDD, LBP, and sciatica as outcomes, this study reveals significant causal relationships of glycerophospholipids, sterols, and glycerolipids with the risk of IVDD, LBP, and sciatica. Phosphatidylcholine, triglycerides, and sterols consistently exerted risk influences on IVDD, while phosphatidylethanolamine (O-16:1_18:2) among glycerophospholipids exhibited a protective effect (OR: 0.927-0.998, P < 0.05). Regarding LBP, sphingomyelin (d38:2) in sphingolipids demonstrated a protective effect (OR: 0.925-0.997, P < 0.05). For sciatica, triglycerides exhibited a risk influence, with varying effects observed for phosphatidylcholine and sterols with different molecular structures. Notably, sterol ester (27:1/16:1) consistently showed a risk effect across all three conditions. Our research provides valuable insights into how certain lipids are linked to the risks of LBP, IVDD, and sciatica. Our findings indicate that phosphatidylcholine and triglycerides may increase the incidence of IVDD, LBP, and sciatica, suggesting potential adverse effects. In contrast, sphingomyelin appears to reduce the occurrence of LBP and sciatica, indicating a protective role. Sterol esters also show a protective effect against sciatica; however, the sterol ester (27:1/16:1) consistently demonstrates a detrimental impact on IVDD, LBP, and sciatica. Additionally, our study underscores the intricate nature of lipid metabolism concerning IVDD, LBP, and sciatica. It uncovers a range of structural variations among lipids and explores how these variations may lead to different effects across various molecular subtypes.
Key numbers
41,669 cases
Intervertebral Disc Degeneration Cases
Total number of cases analyzed for intervertebral disc degeneration.
32,845 cases
Low Back Pain Cases
Total number of cases analyzed for low back pain.
46,707 cases
Sciatica Cases
Total number of cases analyzed for sciatica.
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Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The data used in this paper are publicly available, ethically approved, and the subjects have given their informed consent. Consent for publication: Not applicable.
