Evidence map›Paper›PMID 40828213›Full record

ArticleDiscover mental health2025

Investigating the causal role of serum metabolites in substance use disorder risk: a study integrating Mendelian randomization and synthesis analysis.

WeiXiong Xu, DanDan Xie, ZhenZhu Zhang, PiBo Du, YongJian Ye, XuBo Dai

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Article in Discover mental health, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

WeiXiong Xu *Department of Clinical Laboratory, 910th Hospital of the Chinese People's Liberation Army Joint Logistics Support Force, Quanzhou, 362000, Fujian, China.
DanDan Xie *Department of Clinical Laboratory, 910th Hospital of the Chinese People's Liberation Army Joint Logistics Support Force, Quanzhou, 362000, Fujian, China.
ZhenZhu Zhang *Department of Clinical Laboratory, 910th Hospital of the Chinese People's Liberation Army Joint Logistics Support Force, Quanzhou, 362000, Fujian, China.
PiBo Du *Department of Clinical Laboratory, 910th Hospital of the Chinese People's Liberation Army Joint Logistics Support Force, Quanzhou, 362000, Fujian, China.
YongJian Ye *Department of Clinical Laboratory, 910th Hospital of the Chinese People's Liberation Army Joint Logistics Support Force, Quanzhou, 362000, Fujian, China.
XuBo Dai *Department of Clinical Laboratory, 910th Hospital of the Chinese People's Liberation Army Joint Logistics Support Force, Quanzhou, 362000, Fujian, China. 3771740433@qq.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThis study aimed to explore how serum metabolites affect the risk of substance use disorders (SUD).

methodsIn the initial stage, Mendelian randomization was applied to assess the relationship between 1,400 serum metabolites and SUD. Inverse variance weighting, the Wald ratio odds ratio, and 95% confidence intervals were primarily used to evaluate causal relationships, and the false discovery rate was used for multiple comparison corrections. Sensitivity analysis was conducted via Cochran's Q test and MR-PRESSO. The MR-Steiger test was used to examine reverse causality. In the validation stage, we sought additional GWAS data on SUD to verify the initial results. Furthermore, the pathway enrichment analysis was conducted for known metabolites that exhibited causal relationships with SUD in both phases.

resultsIn the initial phase, we analysis suggests that these 77 metabolites may have potential causal associations with SUD, including 14 metabolite ratios and 63 metabolites (49 known and 14 unknown). In the validation phase, for 57 metabolites (38 known, 6 unknown, 13 ratios), confirmed associations may indicate causal effects on SUD incidence. The synthesis analysis results indicated that the overall effect of the combined metabolites was consistent with the primary analysis with two identified as risk factors and four as protective factors for SUD. Specifically, Erythronate levels, 1-(1-enyl-stearoyl)-2-oleoyl-GPE (P-18:0/18:1) levels, aspartate to citrulline ratios, and cis-4-decenoate (10:1n6) levels were negatively correlated with SUD, whereas gamma-glutamyl-alpha-lysine and ethyl alpha-glucopyranoside levels were positively correlated with disease incidence. The metabolites linked to the risk of SUD in both phases were primarily enriched in several metabolic pathways, including pantothenate and CoA biosynthesis; pyrimidine metabolism; biosynthesis of valine, leucine, and isoleucine; taurine and hypotaurine metabolism; histidine metabolism; and glycerolipid metabolism.

conclusionCirculating metabolites may have a causal relationship with the risk of SUD. "Specific metabolites may be potential biomarkers for SUD, contributing to risk prediction and the development of personalized treatment strategies".

Indexed as

Causal effectsLipid metabolismMendelian randomizationMetabolitesSubstance use disorder

Identifiers

PMID40828213
PMCPMC12364769

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.