{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T03:53:40Z","timestamp":1784260420156,"version":"3.55.0"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T00:00:00Z","timestamp":1701475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172152"],"award-info":[{"award-number":["82172152"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82241044"],"award-info":[{"award-number":["82241044"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Evidence supports the observational correlations between human blood metabolites and sepsis. However, whether these associations represent a causal relationship is unknown. In this study, we applied two\u2010sample Mendelian randomization (MR) analyses to examine causality between genetically proxied 486 blood metabolites and sepsis risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used summary data from genome\u2010wide association studies (GWAS) on 486 metabolites involving 7824 individuals as exposure and a sepsis GWAS including 11,643 cases and 474,841 controls as the outcome. The inverse\u2010variance weighted (IVW) was the primary method to estimate the causal relationship between exposure and outcome, with MR\u2010Egger and weighted median serving as supplements. Sensitivity analyses were implemented with Cochrane's <jats:italic>Q<\/jats:italic> test, MR\u2010Egger intercept, MR\u2010PRESSO and leave\u2010one\u2010out analysis. In addition, we performed replication MR, meta\u2010analysis, Steiger test, linkage disequilibrium score (LDSC) regression and multivariable MR (MVMR) to thoroughly verify the causation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified that genetically determined high levels of 1\u2010oleoylglycerophosphoethanolamine (odds ratio (OR)\u2009=\u2009.52, 95% confidence interval (CI): .31\u2013.87, <jats:italic>p<\/jats:italic>\u2009=\u2009.0122), alpha\u2010glutamyltyrosine (OR\u2009=\u2009.75, 95% CI: .60\u2013.93, <jats:italic>p<\/jats:italic>\u2009=\u2009.0102), heptanoate (7:0) (OR\u2009=\u2009.51, 95% CI: .33\u2013.81, <jats:italic>p<\/jats:italic>\u2009=\u2009.0041) and saccharin (OR\u2009=\u2009.84, 95% CI: .74\u2013.94, <jats:italic>p<\/jats:italic>\u2009=\u2009.0036) were causally associated with a lower risk of sepsis. MVMR analysis demonstrated the independent causal effect of these metabolites on sepsis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings indicated that four blood metabolites have a protective impact on sepsis, thus providing novel perspectives into the metabolite\u2010mediated development mechanism of sepsis by combining genomics and metabolomics.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.14145","type":"journal-article","created":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T19:51:13Z","timestamp":1701546673000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Human blood metabolites and risk of sepsis: A Mendelian randomization investigation"],"prefix":"10.1111","volume":"54","author":[{"given":"Weifeng","family":"Shang","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurology The Third Xiangya Hospital, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sisi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1999-0211","authenticated-orcid":false,"given":"Dechang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32989-7"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000004155"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftac027"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.25"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutres.2018.10.003"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-022-03320-y"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjresp-2014-000056"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo10020070"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyx034"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyg070"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.6022"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12031201"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-022-03648-5"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv071"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2982"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr988"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0579-z"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1004174"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01371-0"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21758"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0099-7"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-017-0255-x"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.22207"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0255-0"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abj8969"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007081"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2022.04.035"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.20468"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-011-1337-4"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwu283"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.18236"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-011-2359-1"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10112412"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-018-1457-2"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-050420-025929"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0907601"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ircmb.2015.10.001"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1159\/000167856"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10059-009-0049-4"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms161025353"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00366.2005"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1177\/0148607113489833"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12061862"}],"container-title":["European Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/eci.14145","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T04:33:20Z","timestamp":1726720400000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/eci.14145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,2]]},"references-count":45,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1111\/eci.14145"],"URL":"https:\/\/doi.org\/10.1111\/eci.14145","archive":["Portico"],"relation":{},"ISSN":["0014-2972","1365-2362"],"issn-type":[{"value":"0014-2972","type":"print"},{"value":"1365-2362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,2]]},"assertion":[{"value":"2023-08-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14145"}}