{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:08:39Z","timestamp":1771394919145,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Research Project of Chongqing Municipal Education Commission","award":["KJQN202400467"],"award-info":[{"award-number":["KJQN202400467"]}]},{"DOI":"10.13039\/501100005230","name":"Chongqing Natural Science Foundation","doi-asserted-by":"crossref","award":["CSTB2024NSCQ-MSX0045"],"award-info":[{"award-number":["CSTB2024NSCQ-MSX0045"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Collaborative Research Fund for Young Scientists Supported by Chongqing Bishan District Bureau of Science and Technology and Chongqing University of Chinese Medicine","award":["BSLHZX034"],"award-info":[{"award-number":["BSLHZX034"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple myeloma (MM) is a clonal plasma cell neoplasm characterized by autonomous immunoglobulin overproduction. Despite associations between serum metabolites and MM, causal mechanisms remain unclear. Here, we employed bidirectional Mendelian randomization (MR) using 452 serum metabolites to elucidate causal associations with MM risk. The inverse variance-weighted (IVW) method was prioritized, complemented by MR-Egger and weighted median (WM) analyses to address horizontal pleiotropy. Sensitivity analyses\u2014including Cochran\u2019s Q test, MR-Egger intercept evaluation, and leave-one-out (LOO) robustness checks\u2014confirmed result stability. Pathway enrichment was performed using MetaboAnalyst 6.0. RNA-seq data were integrated to identify transcriptional regulators and signaling pathways mediating serum metabolite-driven MM. Among 21 metabolites significantly associated with MM, 8 exhibited protective inverse correlations, while 13 showed risk-enhancing effects. Sensitivity analyses further confirmed the validity of the observed relationships, while bidirectional MR confirmed no reverse causality. Pathway enrichment highlighted valine\/leucine\/isoleucine biosynthesis and biotin metabolism as pivotal pathways. Integrating transcriptomic data revealed 11 overlapping genes enriched in metal ion transmembrane transporter activity and glycosaminoglycan biosynthesis\u2014chondroitin sulfate\/dermatan sulfate. This study established a causal relationship between specific serum metabolites and MM and revealed that key genes may affect the development of MM through metabolic-epigenetic crosstalk, providing preliminary insights into potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms27041904","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T11:11:28Z","timestamp":1771240288000},"page":"1904","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating Bidirectional Mendelian Randomization with Multi-Omics Reveals Causal Serum Metabolites and Novel Metabolic Drivers of Multiple Myeloma"],"prefix":"10.3390","volume":"27","author":[{"given":"Yuanheng","family":"Liu","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daoyuan","family":"Qin","sequence":"additional","affiliation":[{"name":"Chongqing College of Traditional Chinese Medicine, Chongqing 402760, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haohan","family":"Ye","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lujun","family":"Tang","sequence":"additional","affiliation":[{"name":"Chongqing College of Traditional Chinese Medicine, Chongqing 402760, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8616-8702","authenticated-orcid":false,"given":"Xiaoli","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China"},{"name":"Laboratory of Developmental Biology, Department of Genetics and Cell Biology, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/S0140-6736(21)00135-5","article-title":"Multiple Myeloma","volume":"397","author":"Pawlyn","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e70067","DOI":"10.1002\/hon.70067","article-title":"Multiple Myeloma Unpacked","volume":"43","author":"Gay","year":"2025","journal-title":"Hematol. 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