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已发表论文
探讨血浆代谢物与坐骨神经痛之间的因果关联：一项双样本孟德尔随机化分析
Authors Yu S, Wei Q, Luo Y, Wu G
Received 14 October 2025
Accepted for publication 22 January 2026
Published 13 February 2026 Volume 2026:19 568746
DOI https://doi.org/10.2147/JPR.S568746
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Alaa Abd-Elsayed
Shaoyong Yu,1 Qiuyu Wei,2 Yi Luo,2 Gang Wu2
1Traumatic Joint First Ward, Liuzhou Traditional Chinese Medicine Hospital, Liuzhou, Guangxi, People’s Republic of China; 2Department of Neurosurgery, Liuzhou Traditional Chinese Medicine Hospital, Liuzhou, Guangxi, People’s Republic of China
Correspondence: Qiuyu Wei, Department of Neurosurgery, Liuzhou Traditional Chinese Medicine Hospital, Liuzhou, 545000, People’s Republic of China, Email 1983432933@qq.com Gang Wu, Department of Neurosurgery, Liuzhou Traditional Chinese Medicine Hospital, Liuzhou, 545000, People’s Republic of China, Email 15877248687@139.com
Background: Sciatica is a prevalent and highly disabling radicular pain syndrome, often involving mixed nociceptive and neuropathic components, which severely impacts patients’ quality of life and work capacity, underscoring the need to identify biomarkers for early intervention. Although recent metabolomics studies have revealed significant associations between altered plasma metabolite levels and sciatica, the causal relationship with plasma metabolites remains unverified. This study aims to analyze the causal association between plasma metabolites and sciatica from a genetic perspective and provide relevant evidence.
Methods: Public datasets comprising 1,400 plasma metabolites (as exposures) and sciatica (as outcome) were collected. Mendelian randomization analyses were performed using Rstudio, incorporating inverse-variance weighted, MR-Egger, weighted median, simple mode, and weighted mode methods. Robustness and reliability were ensured through heterogeneity testing, horizontal pleiotropy assessment, and Steiger directionality tests.
Results: We identified four plasma metabolites with significant causal relationships to sciatica after false discovery rate correction (PFDR < 0.05). Two distinct forms of the bilirubin degradation product C17H20N2O5 were identified as risk factors (Form 1: OR = 1.040, 95% CI = 1.015– 1.066, P = 0.001, PFDR=0.003; Form 2: OR = 1.039, 95% CI = 1.014– 1.065, P = 0.002, PFDR = 0.004). In contrast, N-Acetyl-β-alanine (OR = 0.960, 95% CI = 0.931– 0.991, P = 0.011, PFDR = 0.014) and Glycosyl-N-stearoyl-sphingosine (d18:1/18:0) (OR = 0.953, 95% CI = 0.920– 0.989, P = 0.010, PFDR = 0.012) were protective factors. The analysis was based on 106 independent instrumental variables (single nucleotide polymorphisms).
Conclusion: This study provides genetic evidence supporting a causal role of specific plasma metabolites in sciatica risk, highlighting the involvement of bilirubin and amino acid/sphingolipid metabolism in its pathogenesis. These findings offer novel insights into the biology of sciatica and may inform future research into therapeutic strategies.
Keywords: plasma metabolites, sciatica, causal association, mendelian randomization, genetics, single nucleotide polymorphism, genome-wide association study
1Traumatic Joint First Ward, Liuzhou Traditional Chinese Medicine Hospital, Liuzhou, Guangxi, People’s Republic of China; 2Department of Neurosurgery, Liuzhou Traditional Chinese Medicine Hospital, Liuzhou, Guangxi, People’s Republic of China
Correspondence: Qiuyu Wei, Department of Neurosurgery, Liuzhou Traditional Chinese Medicine Hospital, Liuzhou, 545000, People’s Republic of China, Email 1983432933@qq.com Gang Wu, Department of Neurosurgery, Liuzhou Traditional Chinese Medicine Hospital, Liuzhou, 545000, People’s Republic of China, Email 15877248687@139.com
Background: Sciatica is a prevalent and highly disabling radicular pain syndrome, often involving mixed nociceptive and neuropathic components, which severely impacts patients’ quality of life and work capacity, underscoring the need to identify biomarkers for early intervention. Although recent metabolomics studies have revealed significant associations between altered plasma metabolite levels and sciatica, the causal relationship with plasma metabolites remains unverified. This study aims to analyze the causal association between plasma metabolites and sciatica from a genetic perspective and provide relevant evidence.
Methods: Public datasets comprising 1,400 plasma metabolites (as exposures) and sciatica (as outcome) were collected. Mendelian randomization analyses were performed using Rstudio, incorporating inverse-variance weighted, MR-Egger, weighted median, simple mode, and weighted mode methods. Robustness and reliability were ensured through heterogeneity testing, horizontal pleiotropy assessment, and Steiger directionality tests.
Results: We identified four plasma metabolites with significant causal relationships to sciatica after false discovery rate correction (PFDR < 0.05). Two distinct forms of the bilirubin degradation product C17H20N2O5 were identified as risk factors (Form 1: OR = 1.040, 95% CI = 1.015– 1.066, P = 0.001, PFDR=0.003; Form 2: OR = 1.039, 95% CI = 1.014– 1.065, P = 0.002, PFDR = 0.004). In contrast, N-Acetyl-β-alanine (OR = 0.960, 95% CI = 0.931– 0.991, P = 0.011, PFDR = 0.014) and Glycosyl-N-stearoyl-sphingosine (d18:1/18:0) (OR = 0.953, 95% CI = 0.920– 0.989, P = 0.010, PFDR = 0.012) were protective factors. The analysis was based on 106 independent instrumental variables (single nucleotide polymorphisms).
Conclusion: This study provides genetic evidence supporting a causal role of specific plasma metabolites in sciatica risk, highlighting the involvement of bilirubin and amino acid/sphingolipid metabolism in its pathogenesis. These findings offer novel insights into the biology of sciatica and may inform future research into therapeutic strategies.
Keywords: plasma metabolites, sciatica, causal association, mendelian randomization, genetics, single nucleotide polymorphism, genome-wide association study