{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:56:05Z","timestamp":1790841365297,"version":"4.1.0"},"reference-count":71,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Stroke is a leading cause of global mortality and morbidity, yet its underlying metabolic mechanisms remain largely undefined. Elucidating the causal role of blood metabolites in stroke pathogenesis is crucial for developing effective interventions. This study employed a two\u2010sample Mendelian randomization (MR) framework to investigate the causal relationships between 1400 plasma metabolites and the risk of stroke and its subtypes. We integrated genome\u2010wide association study (GWAS) data on metabolites from 3441 to 8299 European\u2010ancestry individuals in the Canadian Longitudinal Study on Aging (CLSA) with European\u2010ancestry stroke GWAS data from the MEGASTROKE consortium. IVW associations were interpreted together with Benjamini\u2013Hochberg false\u2010discovery\u2010rate (FDR) correction, sensitivity analyses, and mRnd power estimates. The IVW screening analysis identified 235 nominal associations (\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>IVW<\/jats:sub>\n                    \u2009&lt;\u20090.05) across 124 metabolites and ratios. Among the final prioritized findings, plasma free asparagine (OR\u2009=\u20090.852, 95% CI: 0.782\u20130.929, FDR\u2009=\u20090.033) and the glutamine\u2010to\u2010asparagine ratio (OR\u2009=\u20091.148, 95% CI: 1.068\u20131.235, FDR\u2009=\u20090.033) showed FDR\u2010significant associations with cardioembolic stroke. Additional associations for steroid sulfates, bile\u2010acid conjugates, and octadecenedioylcarnitine were nominally significant and supported by directionally consistent sensitivity analyses but did not pass FDR correction. Our MR analysis prioritizes amino\u2010acid metabolism in cardioembolic stroke and suggests additional lipid\u2010related metabolic pathways for follow\u2010up. Because several associations were exploratory after FDR correction and all GWAS datasets were restricted to European ancestry, replication in larger and more diverse populations is warranted before clinical translation.\n                  <\/jats:p>","DOI":"10.1002\/iub.70124","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:01:56Z","timestamp":1790838116000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Causal Associations Between Plasma Metabolites and Stroke Risk Identified by Mendelian Randomization"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0463-4185","authenticated-orcid":false,"given":"Lu","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Traditional Chinese Medicine The First Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"},{"name":"Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu\u2010Moxi and Rehabilitation Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Medical Department Zhejiang Provincial Hospital of Chinese Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0400-3006","authenticated-orcid":false,"given":"Fuyuan","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Acupuncture and Tuina, School of Regimen and Rehabilitation Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baochao","family":"Fan","sequence":"additional","affiliation":[{"name":"Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu\u2010Moxi and Rehabilitation Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Physical Education and Public Health Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2974-1311","authenticated-orcid":false,"given":"Guangpeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology The First Affiliated Hospital, Sun Yat\u2010Sen University  Guangzhou China"},{"name":"School of Medical Imaging Guizhou Medical University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2111-9193","authenticated-orcid":false,"given":"Jinchun","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation The First Affiliated Hospital, Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7821-4699","authenticated-orcid":false,"given":"Liming","family":"Lu","sequence":"additional","affiliation":[{"name":"Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu\u2010Moxi and Rehabilitation Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1177\/17474930231181677","article-title":"The Global Burden of Stroke","volume":"18","author":"Markus H. 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Drug Discovery"},{"key":"e_1_2_13_6_1","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1097\/HM9.0000000000000094","article-title":"Acupuncture for Ischemic Stroke: Where Are We Now?","volume":"4","author":"Zhu W.","year":"2024","journal-title":"Acupuncture and Herbal Medicine"},{"key":"e_1_2_13_7_1","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4939-2377-9","volume-title":"Metabonomics","author":"Bjerrum J. 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