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. 2025 Aug 12;16:1627020. doi: 10.3389/fpsyt.2025.1627020

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Copyright © 2025 Qianhao, Jinwen, Jingjie, Xiaoyu, Yangfei, Wenxiu, Xu, Xiaojun, Peipei and Qi.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Six panels (A–F) show KEGG pathway enrichment and impact analyses from WGCNA and MR-integrated results. Panels A, C, and E are bar plots showing enriched KEGG terms ranked by enrichment scores; key pathways include purine metabolism, glutathione metabolism, and glycine–serine–threonine metabolism. Panels B, D, and F are corresponding bubble plots showing pathway impact vs. –log(p), where bubble size reflects metabolite count. Glycine–serine–threonine and purine pathways consistently show high impact and significance across methods. — Risk forest plot of the results of MR Analysis. (A) GCST90200450: Caproate (6:0) levels; GCST90200786: Cysteine to alanine ratio; GCST90200107: Gamma-glutamyl-alpha-lysine levels; GCST90200208: Glucuronide of piperine metabolite C17H21NO3 (4) levels; GCST90200178: Glucuronide of C10H18O2 (7) levels; GCST90200812: Glutamate to kynurenine ratio; GCST90200965: Glutamate to 5-oxoproline ratio; (B) GCST90200972: Leucine to N-palmitoyl-sphingosine (d18:1 to 16:0) ratio; GCST90200808: Spermidine to choline ratio; GCST90200374: Sphinganine levels; GCST90200206: Sulfate of piperine metabolite C18H21NO3 (1) levels; GCST90199908: 2-o-methylascorbic acid levels; GCST90199716: 10-undecenoate (11:1n1) levels; GCST90200660: X-25957 levels; (C) GCST90200727: Adenosine 3’,5’-cyclic monophosphate (cAMP) to taurocholate ratio; GCST90200830: Cholate to adenosine 3’,5’-cyclic monophosphate (cAMP) ratio; GCST90199697: Dodecanedioate levels; GCST90200185: Gamma-glutamylcitrulline levels; GCST90199970: Octadecenedioylcarnitine (C18:1-DC) levels; GCST90199993: Phenylacetylcarnitine levels; GCST90200838: Phosphate to glutamate ratio; (D) GCST90200779: Pyruvate to N-acetylneuraminate ratio; GCST90200907: Retinol (Vitamin A) to linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) ratio; GCST90200415: Serine levels; GCST90199821: 1-linoleoyl-GPI (18:2) levels; GCST90200087:2-methylserine levels; GCST90199693: 3-hydroxydecanoate levels; GCST90200328: 3-methoxytyrosine levels; (E) GCST90200220: 4-allylcatechol sulfate levels; GCST90200466: X-11632 levels; GCST90200527: X-13866 levels; GCST90200572: X-19299 levels; GCST90200563: X-21355 levels; GCST90200583: X-21807 levels; GCST90200664: X-25810 levels.