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Article(id=1311349976077263458, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1311349919793905738, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202601080, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1767628800000, receivedDateStr=2026-01-06, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1790579798001, onlineDateStr=2026-09-28, pubDate=1782316800000, pubDateStr=2026-06-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1790579798001, onlineIssueDateStr=2026-09-28, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1790579798001, creator=13701087609, updateTime=1790579798001, updator=13701087609, issue=Issue{id=1311349919793905738, tenantId=1146029695717560320, journalId=1227665162245664772, year='2026', volume='53', issue='12', pageStart='2113', pageEnd='2304', issueExtLink='null', onlineDate='null', pubDate='1782316800000', pubDateStr='2026-06-25', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1790579784582, creator='13701087609', updateTime=1790588408144, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1311386089701597565, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1311349919793905738, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1311386089701597566, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1311349919793905738, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=2139, endPage=2144, ext={EN=ArticleExt(id=1311349977692070499, articleId=1311349976077263458, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Mendelian randomization reveals the causal protective effect of phosphatidylcholine on Crohn’s disease and its potential inflammatory regulatory mechanism, columnId=1228016567443718970, journalTitle=Modern Preventive Medicine, columnName=Epidemiology and Statistical Methods Advances, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate the causal relationship between plasma lipidome and Crohn’s disease (CD), and further reveal the potential mediating role of inflammatory factors in the lipid-CD pathogenesis mechanism by integrating genome-wide association study (GWAS) data of inflammatory factors.

Methods

Based on GWAS summary statistics from GeneRISK (n=7 174), SCALLOP (n=14 824), and FinnGen (n=395 179), a two-sample Mendelian randomization (MR) study design was adopted. Using single nucleotide polymorphisms (SNPs) as instrumental variables, the total causal effects of 179 plasma lipid metabolites on CD were first evaluated. Subsequently, a stepwise MR and intersection screening strategy was employed to explore the regulatory pathways involving 91 circulating inflammatory factors. The main statistical method used was the inverse variance weighting (IVW) method, supplemented by sensitivity analyses and multiple testing correction.

Results

The initial MR screening identified 19 lipid phenotypes significantly associated with CD risk. Further analysis pinpointed Phosphatidylcholine (PC 18:1_20:4) as a significant protective factor against CD, with elevated levels robustly causally associated with reduced CD risk. In exploring the mechanism, it was found that this lipid significantly downregulated the expression level of the T-cell surface glycoprotein CD6 (β=-0.054, P<0.05), while genetically elevated CD6 levels significantly increased CD risk (β=0.179, P<0.05). Mediation effect analysis indicated that the CD6-mediated effect direction was consistent with the total effect, accounting for approximately 6.9% of the effect (indirect effect β indirect=-0.010, P=0.396). Reverse MR analysis did not support a reverse causal effect of CD on this lipid.

Conclusion

This study provides genetic evidence confirming the significant protective effect of Phosphatidylcholine (PC 18:1_20:4) against Crohn’s disease. CD6 is identified as a key downstream responder molecule that is negatively regulated by this lipid and promotes CD risk. The results suggest that “phosphatidylcholine—CD6—CD” may be a potential biological pathogenic axis, offering new theoretical foundations for in-depth analysis of the immunometabolic mechanisms of CD and the exploration of intervention targets.

, authors=Qing XU1, Pei-hong LI2, Zhan-cheng LIN1, authorsList=Qing XU, Pei-hong LI, Zhan-cheng LIN, authorCompany=null, correspAuthors=Zhan-cheng LIN, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1311349978795172460, articleId=1311349976077263458, tenantId=1146029695717560320, journalId=1227665162245664772, language=CN, title=孟德尔随机化揭示磷脂酰胆碱对克罗恩病的因果保护作用及其潜在炎症调节机制, columnId=1228016567632462653, journalTitle=现代预防医学, columnName=流行病与统计方法, runingTitle=null, highlight=null, articleAbstract=
目的

探讨血浆脂质组与克罗恩病（Crohn’s disease，CD）之间的因果关联，并结合炎症因子全基因组关联研究（genome-wide association study，GWAS）数据，进一步揭示炎症因子在脂质-CD发病机制中可能发挥的潜在中介作用。

方法

基于GeneRISK（n=7 174）、SCALLOP（n=14 824）及FinnGen（n=395 179）的GWAS汇总统计数据，采用两样本孟德尔随机化（Mendelian randomization, MR）研究设计。以单核苷酸多态性（single nucleotide polymorphism，SNP）为工具变量，首先评估179种血浆脂质代谢物对CD的总因果效应。随后，采用分步MR及交集筛选策略，探究91种循环炎症因子在其中的调控路径。主要统计方法采用逆方差加权法（Inverse variance weighting，IVW），并辅以敏感性分析及多重检验校正。

结果

MR初筛鉴定出19种与CD发病风险显著相关的脂质组表型。进一步分析锁定磷脂酰胆碱（Phosphatidylcholine, PC 18:1_20:4）为CD发病的显著保护因素，其水平升高与CD风险降低存在稳健的因果关联。在机制探索中，发现该脂质显著下调了T细胞表面糖蛋白CD6的表达水平（β=-0.054，P<0.05），而CD6水平的遗传性升高则显著增加CD发病风险（β=0.179，P<0.05）。中介效应分析显示，CD6介导的效应方向与总效应一致，效应占比约为6.9%（间接效应值βindirect=-0.010，P=0.396）。反向MR分析不支持CD对该脂质存在反向因果效应。

结论

本研究从遗传学角度证实磷脂酰胆碱（PC 18:1_20:4）对克罗恩病具有显著的保护作用。CD6被识别为受该脂质负向调控、且能促进CD风险的关键下游应答分子。结果提示“磷脂酰胆碱—CD6—CD”可能是一条潜在的生物学致病轴线，为深入解析CD的免疫代谢机制及挖掘干预靶点提供了新的理论依据。

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徐晴（1995-），女，硕士，主治医师，研究方向：中医药干预各类慢性疾病研究

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林展铖，E-mail:
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journalName=Lancet, refType=null, unstructuredReference=Torres J, Mehandru S, Colombel JF, et al. Crohn’s disease［J］. Lancet, 2017, 389(10080): 1741-1755., articleTitle=Crohn’s disease, refAbstract=null), Reference(id=1311349983635399325, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2019, volume=9, issue=11, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[2], rfOrder=1, authorNames=Safarpour AR, Mehrabi M, Keshtkar A, journalName=BMJ Open, refType=null, unstructuredReference=Safarpour AR, Mehrabi M, Keshtkar A, et al. Systematic review and meta-analysis of the incidence and prevalence and 30-year trend of inflammatory bowel diseases in Asia: a study protocol［J］. BMJ Open, 2019, 9(11): e031854., articleTitle=Systematic review and meta-analysis of the incidence and prevalence and 30-year trend of inflammatory bowel diseases in Asia: a study protocol, refAbstract=null), Reference(id=1311349983689925278, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2018, volume=24, issue=1, pageStart=15, pageEnd=22, url=null, language=null, rfNumber=[3], rfOrder=2, authorNames=Li N, Shi RH, journalName=World Journal of Gastroenterology, refType=null, unstructuredReference=Li N, Shi RH. Updated review on immune factors in pathogenesis of Crohn’s disease［J］. World Journal of Gastroenterology, 2018, 24(1): 15-22., articleTitle=Updated review on immune factors in pathogenesis of Crohn’s disease, refAbstract=null), Reference(id=1311349983752839839, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2019, volume=10, issue=null, pageStart=277, pageEnd=null, url=null, language=null, rfNumber=[4], rfOrder=3, authorNames=Parada venegas D, De la Fuente MK, Landskron G, journalName=Frontiers in Immunology, refType=null, unstructuredReference=Parada venegas D, De la Fuente MK, Landskron G, et al. Short chain fatty acids (SCFAs)-Mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases［J］. Frontiers in Immunology, 2019, 10: 277., articleTitle=Short chain fatty acids (SCFAs)-Mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases, refAbstract=null), Reference(id=1311349983836725920, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2010, volume=4, issue=6, pageStart=478, pageEnd=482, url=null, language=null, rfNumber=[5], rfOrder=4, authorNames=Sappati biyyani RSR, Putka BS, Mullen KD, journalName=Journal of Clinical Lipidology, refType=null, unstructuredReference=Sappati biyyani RSR, Putka BS, Mullen KD. Dyslipidemia and lipoprotein profiles in patients with inflammatory bowel disease［J］. Journal of Clinical Lipidology, 2010, 4(6): 478-482., articleTitle=Dyslipidemia and lipoprotein profiles in patients with inflammatory bowel disease, refAbstract=null), Reference(id=1311349983924806305, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2016, volume=61, issue=3, pageStart=865, pageEnd=871, url=null, language=null, rfNumber=[6], rfOrder=5, authorNames=Koutroumpakis E, Ramos-Rivers C, Regueiro M, journalName=Digestive Diseases and Sciences, refType=null, unstructuredReference=Koutroumpakis E, Ramos-Rivers C, Regueiro M, et al. Association between Long-Term lipid profiles and disease severity in a large cohort of patients with inflammatory bowel disease［J］. Digestive Diseases and Sciences, 2016, 61(3): 865-871., articleTitle=Association between Long-Term lipid profiles and disease severity in a large cohort of patients with inflammatory bowel disease, refAbstract=null), Reference(id=1311349983991915170, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2021, volume=326, issue=16, pageStart=1614, pageEnd=1621, url=null, language=null, rfNumber=[7], rfOrder=6, authorNames=Skrivankova VW, Richmond RC, Woolf BAR, journalName=the Journal of the American Medical Association, refType=null, unstructuredReference=Skrivankova VW, Richmond RC, Woolf BAR, et al. Strengthening the reporting of observational studies in epidemiology using mendelian randomization: the STROBE-MR statement［J］. the Journal of the American Medical Association, 2021, 326(16): 1614-1621., articleTitle=Strengthening the reporting of observational studies in epidemiology using mendelian randomization: the STROBE-MR statement, refAbstract=null), Reference(id=1311349984063218339, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2021, volume=36, issue=5, pageStart=465, pageEnd=478, url=null, language=null, rfNumber=[8], rfOrder=7, authorNames=Carter AR, Sanderson E, Hammerton G, journalName=European Journal of Epidemiology, refType=null, unstructuredReference=Carter AR, Sanderson E, Hammerton G, et al. Mendelian randomisation for mediation analysis: current methods and challenges for implementation［J］. European Journal of Epidemiology, 2021, 36(5): 465-478., articleTitle=Mendelian randomisation for mediation analysis: current methods and challenges for implementation, refAbstract=null), Reference(id=1311349984126132900, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2016, volume=23, issue=3, pageStart=492, pageEnd=504, url=null, language=null, rfNumber=[9], rfOrder=8, authorNames=Wang B, Rong X, Duerr MA, journalName=Cell Metabolism, refType=null, unstructuredReference=Wang B, Rong X, Duerr MA, et al. Intestinal phospholipid remodeling is required for Dietary-Lipid uptake and survival on a High-Fat Diet［J］. Cell Metabolism, 2016, 23(3): 492-504., articleTitle=Intestinal phospholipid remodeling is required for Dietary-Lipid uptake and survival on a High-Fat Diet, refAbstract=null), Reference(id=1311349984201630373, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2025, volume=104, issue=22, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[10], rfOrder=9, authorNames=Ling K, Zhang S, Jin L, journalName=Medicine, refType=null, unstructuredReference=Ling K, Zhang S, Jin L, et al. Blood metabolomic and Crohn’s disease: A Mendelian randomization study［J］. Medicine, 2025, 104(22): e42684., articleTitle=Blood metabolomic and Crohn’s disease: A Mendelian randomization study, refAbstract=null), Reference(id=1311349984256156326, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2024, volume=14, issue=1, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[11], rfOrder=10, authorNames=Long XQ, Zhang YY, Liu MZ, journalName=Scientific Reports, refType=null, unstructuredReference=Long XQ, Zhang YY, Liu MZ, et al. Causality of genetically determined blood metabolites on inflammatory bowel disease: a two-sample Mendelian randomization study［J］. Scientific Reports, 2024, 14(1): 16361., articleTitle=Causality of genetically determined blood metabolites on inflammatory bowel disease: a two-sample Mendelian randomization study, refAbstract=null), Reference(id=1311349984310682279, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2006, volume=1758, issue=12, pageStart=1864, pageEnd=1884, url=null, language=null, rfNumber=[12], rfOrder=11, authorNames=Zheng WJ, Kollmeyer J, Symolon H, journalName=BBA-Biomembranes, refType=null, unstructuredReference=Zheng WJ, Kollmeyer J, Symolon H, et al. Ceramides and other bioactive sphingolipid backbones in health and disease: Lipidomic analysis, metabolism and roles in membrane structure, dynamics, signaling and autophagy［J］. BBA-Biomembranes, 2006, 1758(12): 1864-1884., articleTitle=Ceramides and other bioactive sphingolipid backbones in health and disease: Lipidomic analysis, metabolism and roles in membrane structure, dynamics, signaling and autophagy, refAbstract=null), Reference(id=1311349984381985448, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2012, volume=30, issue=Suppl 3, pageStart=85, pageEnd=91, url=null, language=null, rfNumber=[13], rfOrder=12, authorNames=Stremmel W, Ehehalt R, Staffer S, journalName=Digestive Diseases, refType=null, unstructuredReference=Stremmel W, Ehehalt R, Staffer S, et al. Mucosal protection by phosphatidylcholine［J］. Digestive Diseases, 2012, 30(Suppl 3): 85-91., articleTitle=Mucosal protection by phosphatidylcholine, refAbstract=null), Reference(id=1311349984453288617, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2020, volume=68, issue=50, pageStart=14884, pageEnd=14895, url=null, language=null, rfNumber=[14], rfOrder=13, authorNames=Tan W, Zhang QJ, Dong ZJ, journalName=Journal of Agricultural and Food Chemistry, refType=null, unstructuredReference=Tan W, Zhang QJ, Dong ZJ, et al. Phosphatidylcholine ameliorates LPS-Induced systemic inflammation and cognitive impairments via mediating the Gut-Brain axis balance［J］. Journal of Agricultural and Food Chemistry, 2020, 68(50): 14884-14895., articleTitle=Phosphatidylcholine ameliorates LPS-Induced systemic inflammation and cognitive impairments via mediating the Gut-Brain axis balance, refAbstract=null), Reference(id=1311349984541369002, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2019, volume=29, issue=6, pageStart=1350, pageEnd=1362.e7, url=null, language=null, rfNumber=[15], rfOrder=14, authorNames=Sanchez-Lopez E, Zhong ZY, Stubelius A, journalName=Cell Metabolism, refType=null, unstructuredReference=Sanchez-Lopez E, Zhong ZY, Stubelius A, et al. Choline uptake and metabolism modulate macrophage IL-1β and IL-18 production［J］. Cell Metabolism, 2019, 29(6): 1350-1362.e7., articleTitle=Choline uptake and metabolism modulate macrophage IL-1β and IL-18 production, refAbstract=null), Reference(id=1311349984604283563, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2015, volume=56, issue=null, pageStart=111, pageEnd=117, url=null, language=null, rfNumber=[16], rfOrder=15, authorNames=Ben-Ami shor D, Bashi T, Lachnish J, journalName=Journal of Autoimmunity, refType=null, unstructuredReference=Ben-Ami shor D, Bashi T, Lachnish J, et al. Phosphorylcholine-tuftsin compoundprevents development of dextransulfate-sodium-salt induced murine colitis: implications for the treatment of human inflammatory bowel disease［J］. Journal of Autoimmunity, 2015, 56: 111-117., articleTitle=Phosphorylcholine-tuftsin compoundprevents development of dextransulfate-sodium-salt induced murine colitis: implications for the treatment of human inflammatory bowel disease, refAbstract=null), Reference(id=1311349984675586732, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2025, volume=13, issue=9, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[17], rfOrder=16, authorNames=Yin LL, Zhu Y, Kong F, journalName=Food Science & Nutrition, refType=null, unstructuredReference=Yin LL, Zhu Y, Kong F, et al. Causal association of plasma lipidome with inflammatory bowel diseases and mediating role of circulating inflammatory proteins: a mendelian randomization study［J］. Food Science & Nutrition, 2025, 13(9): e70916., articleTitle=Causal association of plasma lipidome with inflammatory bowel diseases and mediating role of circulating inflammatory proteins: a mendelian randomization study, refAbstract=null), Reference(id=1311349984759472813, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2025, volume=186, issue=10, pageStart=993, pageEnd=1008, url=null, language=null, rfNumber=[18], rfOrder=17, authorNames=Tian Y, Wang F, Chen L, journalName=International Archives of Allergy and Immunology, refType=null, unstructuredReference=Tian Y, Wang F, Chen L, et al. Identifying novel inflammatory protein biomarkers and drug targets of inflammatory bowel disease by integrating mendelian randomization, bioinformatics, and druggability analysis［J］. International Archives of Allergy and Immunology, 2025, 186(10): 993-1008., articleTitle=Identifying novel inflammatory protein biomarkers and drug targets of inflammatory bowel disease by integrating mendelian randomization, bioinformatics, and druggability analysis, refAbstract=null), Reference(id=1311349984872719022, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2012, volume=491, issue=7422, pageStart=119, pageEnd=124, url=null, language=null, rfNumber=[19], rfOrder=18, authorNames=Jostins L, Ripke S, Weersma RK, journalName=Nature, refType=null, unstructuredReference=Jostins L, Ripke S, Weersma RK, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease［J］. Nature, 2012, 491(7422): 119-124., articleTitle=Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease, refAbstract=null), Reference(id=1311349986042929839, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2017, volume=12, issue=7, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[20], rfOrder=19, authorNames=Bughani U, Saha A, Kuriakose A, journalName=PLOS One, refType=null, unstructuredReference=Bughani U, Saha A, Kuriakose A, et al. T cell activation and differentiation is modulated by a CD6 domain 1 antibody Itolizumab［J］. PLOS One, 2017, 12(7): e0180088., articleTitle=T cell activation and differentiation is modulated by a CD6 domain 1 antibody Itolizumab, refAbstract=null), Reference(id=1311349986546246320, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=2007, volume=104, issue=28, pageStart=11724, pageEnd=11729, url=null, language=null, rfNumber=[21], rfOrder=20, authorNames=Sarrias MR, Farnós M, Mota R, journalName=Proceedings of the National Academy of Sciences of the United States of America, refType=null, unstructuredReference=Sarrias MR, Farnós M, Mota R, et al. CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock［J］. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104(28): 11724-11729., articleTitle=CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock, refAbstract=null), Reference(id=1311349986638521009, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, doi=null, pmid=null, pmcid=null, year=1989, volume=66, issue=1, pageStart=90, pageEnd=95, url=null, language=null, rfNumber=[22], rfOrder=21, authorNames=Smart CJ, Heatley RV, Trejdosiewicz LK, journalName=Immunology, refType=null, unstructuredReference=Smart CJ, Heatley RV, Trejdosiewicz LK. Expression of CD6 and the UCHL1-defined CD45 (p180) antigen by human colonic T lymphocytes［J］. Immunology, 1989, 66(1): 90-95., articleTitle=Expression of CD6 and the UCHL1-defined CD45 (p180) antigen by human colonic T lymphocytes, refAbstract=null)], funds=[Fund(id=1311349983484404379, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, awardId=XH40204-20250471, language=CN, fundingSource=2025年学科人才建设费(XH40204-20250471), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1311349978988110445, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, xref=1., ext=[AuthorCompanyExt(id=1311349978996499054, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, companyId=1311349978988110445, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Critical Care Medicine, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China), AuthorCompanyExt(id=1311349979000693359, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, companyId=1311349978988110445, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.上海中医药大学附属龙华医院重症医学科，上海 200032)]), AuthorCompany(id=1311349979071996528, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, xref=2., ext=[AuthorCompanyExt(id=1311349979080385137, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, companyId=1311349979071996528, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.上海中医药大学附属龙华医院脾胃病科)])], figs=[ArticleFig(id=1311349982188364427, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, language=EN, label=Fig.1, caption=Researchdesign flowchart, figureFileSmall=bx6L7IkFychhFrAu7/5tYg==, figureFileBig=4b95ED5PAGf5LgkSU5ltDg==, tableContent=null), ArticleFig(id=1311349982259667596, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, language=CN, label=图1, caption=研究设计流程

注：a: 179种脂质组对91种炎症相关蛋白的总效应；b: 91种炎症相关蛋白对CD的总效应；c: 179种脂质组对CD的总效应；d: CD对179种脂质组的总效应；c’: 179种脂质组对CD的直接效应（c’=c-a×b）。

, figureFileSmall=bx6L7IkFychhFrAu7/5tYg==, figureFileBig=4b95ED5PAGf5LgkSU5ltDg==, tableContent=null), ArticleFig(id=1311349982452605581, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, language=EN, label=Fig.2, caption=Mendelian randomization analysis of 19 lipid metabolites and the risk of CD onset, figureFileSmall=WXkuq2wW1I1rWZI4RfR0Ww==, figureFileBig=Ln2g+1DOruKOSLcWKHFhQA==, tableContent=null), ArticleFig(id=1311349982523908750, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, language=CN, label=图2, caption=19种脂质代谢物与CD发病风险的孟德尔随机化分析, figureFileSmall=WXkuq2wW1I1rWZI4RfR0Ww==, figureFileBig=Ln2g+1DOruKOSLcWKHFhQA==, tableContent=null), ArticleFig(id=1311349982586823311, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, language=EN, label=Fig.3, caption=Overview of the 14 potential downstream inflammatory targets significantly regulated by PC （18:1_20:4）, figureFileSmall=nL2Rr+nlC1ddJk/7HsOiBw==, figureFileBig=2M3rsq8uBmkBmg/G7TkGzA==, tableContent=null), ArticleFig(id=1311349982721041040, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, language=CN, label=图3, caption=PC （18:1/20:4）显著调控的14种潜在下游炎症靶点概览, figureFileSmall=nL2Rr+nlC1ddJk/7HsOiBw==, figureFileBig=2M3rsq8uBmkBmg/G7TkGzA==, tableContent=null), ArticleFig(id=1311349982779761297, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, language=EN, label=Fig.4, caption=Mendelian randomization analyses for potential causal links between inflammatory factors and Crohn’s disease, figureFileSmall=pM3QqqyWChLeyXHWFBGKjw==, figureFileBig=VcX4NXi9ZYOUVPcWvTI/dw==, tableContent=null), ArticleFig(id=1311349982846870162, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, language=CN, label=图4, caption=针对炎症因子与克罗恩病之间潜在因果关系的孟德尔随机化分析, figureFileSmall=pM3QqqyWChLeyXHWFBGKjw==, figureFileBig=VcX4NXi9ZYOUVPcWvTI/dw==, tableContent=null), ArticleFig(id=1311349982913979027, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, language=EN, label=Table 1, caption=

Details of GWAS summary statistics included in the analysis

, figureFileSmall=null, figureFileBig=null, tableContent=
性状研究联盟/机构族裔样本量
179种血浆脂质代谢物芬兰健康与福利研究所生物库欧洲裔7 174
91种炎症相关蛋白心血管流行病学研究组欧洲裔14 824
克罗恩病FinnGen项目欧洲裔395 178
), ArticleFig(id=1311349982976893588, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, language=CN, label=表1, caption=

纳入分析的GWAS汇总统计数据详细信息

, figureFileSmall=null, figureFileBig=null, tableContent=
性状研究联盟/机构族裔样本量
179种血浆脂质代谢物芬兰健康与福利研究所生物库欧洲裔7 174
91种炎症相关蛋白心血管流行病学研究组欧洲裔14 824
克罗恩病FinnGen项目欧洲裔395 178
), ArticleFig(id=1311349983035613845, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, language=EN, label=Table 2, caption=

Heterogeneity tests and pleiotropy analyses for the causal effects of 19 lipid metabolites on Crohn’s disease

, figureFileSmall=null, figureFileBig=null, tableContent=
暴露因素MR-PRESSO
P值		异质性检验多效性检验BWMR
P值
Cochran QP值Egger interceptP值
磷脂酰胆碱18:0/20:40.30332.6420.2920.0090.6820.007
磷脂酰乙醇胺16:0/18:10.51426.7910.4750.0060.7470.019
磷脂酰胆碱18:1/20:40.28432.6440.2090.0130.3760.007
甾醇酯27:1/20:50.06739.1230.0360.0050.7570.027
醚型磷脂酰胆碱17:0/17:10.26337.6930.2250.0040.8410.006
醚型磷脂酰胆碱18:0/18:20.15327.9950.1100.0240.2870.036
二酰甘油16:0/18:20.17734.1750.161-0.0100.6320.025
磷脂酰肌醇18:0/18:10.22132.0370.192-0.0080.7440.038
磷脂酰肌醇16:0/20:40.55649.4230.0040.0080.6070.002
溶酶磷脂酰胆碱20:40.49025.2030.5080.0030.8180.019
磷脂酰肌醇16:0/18:10.60047.4070.0030.0240.4190.005
磷脂酰乙醇胺18:1/20:40.03545.1400.0290.0270.2350.001
磷脂酰胆碱16:0/20:40.24429.7020.158-0.0030.8360.016
磷脂酰胆碱18:1/20:40.25220.5770.246-0.0020.9330.070
磷脂酰胆碱14:0/18:20.02241.3190.021-0.0480.0720.036
醚型磷脂酰乙醇胺16:0/18:10.11031.5730.1090.0420.1200.018
磷脂酰乙醇胺18:1/20:40.06431.8090.0610.0300.3040.002
磷脂酰胆碱16:0/20:50.25927.7270.2260.0060.7190.024
磷脂酰胆碱18:1/18:30.55716.2540.5750.0220.3980.049
), ArticleFig(id=1311349983115305622, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, language=CN, label=表2, caption=

19种脂质代谢物对克罗恩病因果效应的异质性检验与多效性分析

, figureFileSmall=null, figureFileBig=null, tableContent=
暴露因素MR-PRESSO
P值		异质性检验多效性检验BWMR
P值
Cochran QP值Egger interceptP值
磷脂酰胆碱18:0/20:40.30332.6420.2920.0090.6820.007
磷脂酰乙醇胺16:0/18:10.51426.7910.4750.0060.7470.019
磷脂酰胆碱18:1/20:40.28432.6440.2090.0130.3760.007
甾醇酯27:1/20:50.06739.1230.0360.0050.7570.027
醚型磷脂酰胆碱17:0/17:10.26337.6930.2250.0040.8410.006
醚型磷脂酰胆碱18:0/18:20.15327.9950.1100.0240.2870.036
二酰甘油16:0/18:20.17734.1750.161-0.0100.6320.025
磷脂酰肌醇18:0/18:10.22132.0370.192-0.0080.7440.038
磷脂酰肌醇16:0/20:40.55649.4230.0040.0080.6070.002
溶酶磷脂酰胆碱20:40.49025.2030.5080.0030.8180.019
磷脂酰肌醇16:0/18:10.60047.4070.0030.0240.4190.005
磷脂酰乙醇胺18:1/20:40.03545.1400.0290.0270.2350.001
磷脂酰胆碱16:0/20:40.24429.7020.158-0.0030.8360.016
磷脂酰胆碱18:1/20:40.25220.5770.246-0.0020.9330.070
磷脂酰胆碱14:0/18:20.02241.3190.021-0.0480.0720.036
醚型磷脂酰乙醇胺16:0/18:10.11031.5730.1090.0420.1200.018
磷脂酰乙醇胺18:1/20:40.06431.8090.0610.0300.3040.002
磷脂酰胆碱16:0/20:50.25927.7270.2260.0060.7190.024
磷脂酰胆碱18:1/18:30.55716.2540.5750.0220.3980.049
), ArticleFig(id=1311349983186608791, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1311349976077263458, language=EN, label=Table 3, caption=

Heterogeneity tests and pleiotropy analyses for Mendelian randomization estimates for the impact of PC （18:1/20:4） on the identified downstream inflammatory factors

, figureFileSmall=null, figureFileBig=null, tableContent=
结局因素MR-PRESSO
P值		异质性检验多效性检验BWMR
P值
Cochran QP值Egger interceptP值
TRAIL0.04942.3600.0230.0120.066<0.001
CXCL90.69417.7210.8860.0050.2890.003
OSM0.34128.6110.3290.0100.0580.011
DNER0.85917.1670.9040.0030.5670.017
SCF0.958155.376<0.0010.0060.6510.017
Beta-NGF0.23632.0370.1920.0060.3070.026
CD60.38546.5760.008-0.0080.2150.027
MMP-10.47727.4090.3880.0070.1670.029
Flt3L0.08739.8610.040-0.0090.1620.030
uPA0.12037.6180.066-0.0050.4250.032
VEGF-A0.41623.4490.6070.0100.0520.033
CXCL60.58222.0250.6870.0080.1070.039
OPG0.04044.5500.0130.0020.8010.042
CXCL100.77519.0350.8350.0070.1760.047
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PC （18:1/20:4）对鉴定的下游炎症因子影响的孟德尔随机化异质性检验与多效性分析

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结局因素MR-PRESSO
P值		异质性检验多效性检验BWMR
P值
Cochran QP值Egger interceptP值
TRAIL0.04942.3600.0230.0120.066<0.001
CXCL90.69417.7210.8860.0050.2890.003
OSM0.34128.6110.3290.0100.0580.011
DNER0.85917.1670.9040.0030.5670.017
SCF0.958155.376<0.0010.0060.6510.017
Beta-NGF0.23632.0370.1920.0060.3070.026
CD60.38546.5760.008-0.0080.2150.027
MMP-10.47727.4090.3880.0070.1670.029
Flt3L0.08739.8610.040-0.0090.1620.030
uPA0.12037.6180.066-0.0050.4250.032
VEGF-A0.41623.4490.6070.0100.0520.033
CXCL60.58222.0250.6870.0080.1070.039
OPG0.04044.5500.0130.0020.8010.042
CXCL100.77519.0350.8350.0070.1760.047
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Heterogeneity and pleiotropy tests in the MR analyses of inflammatory factors on Crohn’s disease

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暴露因素MR-PRESSO
P值		异质性检验多效性检验BWMR
P值
Cochran QP值Egger interceptP值
CD60.16432.5980.088-0.0090.5970.005
Fit3L0.27650.1150.2440.0080.5200.045
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炎症因子对克罗恩病影响的MR分析异质性与多效性检验

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P值
Cochran QP值Egger interceptP值
CD60.16432.5980.088-0.0090.5970.005
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孟德尔随机化揭示磷脂酰胆碱对克罗恩病的因果保护作用及其潜在炎症调节机制
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徐晴 1 , 李沛鸿 2 , 林展铖 1
现代预防医学 | 流行病与统计方法 2026,53(12): 2139-2144
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现代预防医学 |流行病与统计方法 2026 , 53 (12) : 2139 -2144
孟德尔随机化揭示磷脂酰胆碱对克罗恩病的因果保护作用及其潜在炎症调节机制
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徐晴（1995-），女，硕士，主治医师，研究方向：中医药干预各类慢性疾病研究

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徐晴1, 李沛鸿2, 林展铖1
作者信息
  • 1.上海中医药大学附属龙华医院重症医学科，上海 200032
  • 2.上海中医药大学附属龙华医院脾胃病科
通讯作者:
林展铖，E-mail:
作者简介:

徐晴（1995-），女，硕士，主治医师，研究方向：中医药干预各类慢性疾病研究

Mendelian randomization reveals the causal protective effect of phosphatidylcholine on Crohn’s disease and its potential inflammatory regulatory mechanism
Qing XU1, Pei-hong LI2, Zhan-cheng LIN1
Affiliations
  • Department of Critical Care Medicine, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
出版时间: 2026-06-25 doi: 10.20043/j.cnki.MPM.202601080
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摘要
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目的

探讨血浆脂质组与克罗恩病（Crohn’s disease，CD）之间的因果关联，并结合炎症因子全基因组关联研究（genome-wide association study，GWAS）数据，进一步揭示炎症因子在脂质-CD发病机制中可能发挥的潜在中介作用。

方法

基于GeneRISK（n=7 174）、SCALLOP（n=14 824）及FinnGen（n=395 179）的GWAS汇总统计数据，采用两样本孟德尔随机化（Mendelian randomization, MR）研究设计。以单核苷酸多态性（single nucleotide polymorphism，SNP）为工具变量，首先评估179种血浆脂质代谢物对CD的总因果效应。随后，采用分步MR及交集筛选策略，探究91种循环炎症因子在其中的调控路径。主要统计方法采用逆方差加权法（Inverse variance weighting，IVW），并辅以敏感性分析及多重检验校正。

结果

MR初筛鉴定出19种与CD发病风险显著相关的脂质组表型。进一步分析锁定磷脂酰胆碱（Phosphatidylcholine, PC 18:1_20:4）为CD发病的显著保护因素，其水平升高与CD风险降低存在稳健的因果关联。在机制探索中，发现该脂质显著下调了T细胞表面糖蛋白CD6的表达水平（β=-0.054，P<0.05），而CD6水平的遗传性升高则显著增加CD发病风险（β=0.179，P<0.05）。中介效应分析显示，CD6介导的效应方向与总效应一致，效应占比约为6.9%（间接效应值βindirect=-0.010，P=0.396）。反向MR分析不支持CD对该脂质存在反向因果效应。

结论

本研究从遗传学角度证实磷脂酰胆碱（PC 18:1_20:4）对克罗恩病具有显著的保护作用。CD6被识别为受该脂质负向调控、且能促进CD风险的关键下游应答分子。结果提示“磷脂酰胆碱—CD6—CD”可能是一条潜在的生物学致病轴线，为深入解析CD的免疫代谢机制及挖掘干预靶点提供了新的理论依据。

克罗恩病  /  脂质组  /  炎症因子  /  孟德尔随机化  /  中介效应
Objective

To investigate the causal relationship between plasma lipidome and Crohn’s disease (CD), and further reveal the potential mediating role of inflammatory factors in the lipid-CD pathogenesis mechanism by integrating genome-wide association study (GWAS) data of inflammatory factors.

Methods

Based on GWAS summary statistics from GeneRISK (n=7 174), SCALLOP (n=14 824), and FinnGen (n=395 179), a two-sample Mendelian randomization (MR) study design was adopted. Using single nucleotide polymorphisms (SNPs) as instrumental variables, the total causal effects of 179 plasma lipid metabolites on CD were first evaluated. Subsequently, a stepwise MR and intersection screening strategy was employed to explore the regulatory pathways involving 91 circulating inflammatory factors. The main statistical method used was the inverse variance weighting (IVW) method, supplemented by sensitivity analyses and multiple testing correction.

Results

The initial MR screening identified 19 lipid phenotypes significantly associated with CD risk. Further analysis pinpointed Phosphatidylcholine (PC 18:1_20:4) as a significant protective factor against CD, with elevated levels robustly causally associated with reduced CD risk. In exploring the mechanism, it was found that this lipid significantly downregulated the expression level of the T-cell surface glycoprotein CD6 (β=-0.054, P<0.05), while genetically elevated CD6 levels significantly increased CD risk (β=0.179, P<0.05). Mediation effect analysis indicated that the CD6-mediated effect direction was consistent with the total effect, accounting for approximately 6.9% of the effect (indirect effect β indirect=-0.010, P=0.396). Reverse MR analysis did not support a reverse causal effect of CD on this lipid.

Conclusion

This study provides genetic evidence confirming the significant protective effect of Phosphatidylcholine (PC 18:1_20:4) against Crohn’s disease. CD6 is identified as a key downstream responder molecule that is negatively regulated by this lipid and promotes CD risk. The results suggest that “phosphatidylcholine—CD6—CD” may be a potential biological pathogenic axis, offering new theoretical foundations for in-depth analysis of the immunometabolic mechanisms of CD and the exploration of intervention targets.

Crohn’s disease  /  Lipidome  /  Inflammatory factors  /  Mendelian randomization  /  Mediation effect
徐晴, 李沛鸿, 林展铖. 孟德尔随机化揭示磷脂酰胆碱对克罗恩病的因果保护作用及其潜在炎症调节机制. 现代预防医学, 2026 , 53 (12) : 2139 -2144 . DOI: 10.20043/j.cnki.MPM.202601080
Qing XU, Pei-hong LI, Zhan-cheng LIN. Mendelian randomization reveals the causal protective effect of phosphatidylcholine on Crohn’s disease and its potential inflammatory regulatory mechanism[J]. Modern Preventive Medicine, 2026 , 53 (12) : 2139 -2144 . DOI: 10.20043/j.cnki.MPM.202601080
正文
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克罗恩病（Crohn’s disease, CD）是一种病因未明、主要累及回肠末端和结肠的慢性炎症性肉芽肿性疾病。其临床病程呈慢性复发性特征，病变呈跳跃性分布，除典型的腹痛、腹泻及肠梗阻等消化道症状外，常伴有多器官的肠外表现［1］。据统计，北美和欧洲地区的CD患病率约为29.3/10万，近年来亚洲地区的发病率亦呈迅速上升趋势，且呈现发病年轻化的特征［2］。目前学术界公认CD是由环境、肠道微生态、免疫调节以及遗传易感性多因素交互作用所致，但具体启动机制尚未完全阐明［3］。
近年来，脂质组学在肠道黏膜屏障功能中的核心地位逐渐显现。脂质不仅是细胞膜结构的基础成分，更作为信号分子参与炎症级联反应。脂质谢紊乱可能通过改变膜流动性、增加上皮渗透性以及诱导促炎细胞因子释放，成为CD发病的潜在始动因素之一［4］。然而，目前研究结果充满了复杂性和矛盾性。一方面，系统性炎症状态会继发性地干扰脂质代谢；另一方面，临床观察得出的脂质特征并不一致［5-6］。这种临床表型的不一致性主要归因于传统观察性研究无法克服的局限性，包括样本量不足、混杂因素、反向因果偏倚。因此目前研究很难区分血脂异常究竟是CD导致的“果”，还是诱发CD的“因”，这阻碍了基于脂质代谢途径的治疗策略开发。因此，在排除了环境和生活方式混杂干扰的前提下，从遗传学角度探究脂质组与CD之间真实的因果关联显得尤为迫切。
随着全基因组关联研究（genome-wide association study, GWAS）的进展，超过300个与CD风险相关的遗传位点已被识别，为孟德尔随机化（Mendelian Randomization, MR）分析提供了基础。MR方法遵循“亲代等位基因随机分配”的法则，将与暴露因素（如：血脂水平）强相关的遗传变异作为工具变量（Instrumental Variables, IVs）。MR能够有效地推断暴露与结局之间的因果关系，在证据等级上优于观察性研究［7］。
本研究旨在利用两样本MR分析系统评估不同血脂性状与CD发病风险之间的因果关系。考虑到脂质可能通过调节免疫炎症反应发挥作用，本研究还采用中介分析探讨炎症因子的中介效应。通过阐明“脂质代谢—炎症因子—CD”这一潜在轴线，本研究期望为CD的早期风险分层及代谢干预靶点提供新的理论依据。
1　对象与方法
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1.1　研究对象
本研究采用两样本孟德尔随机化设计，以遗传变异作为IVs，探究脂质组与CD之间的因果关联，并进一步分析炎症因子在其中的中介作用。本研究严格遵循MR分析的三大核心假设：（1）关联性假设：工具变量与暴露因素（脂质组）呈强相关；（2）独立性假设：工具变量与混杂因素无相关性；（3）排他性假设：工具变量仅通过暴露因素影响结局，而不涉及其他途径。研究流程分为三个阶段：第一阶段，评估179种脂质组表型对CD发病风险的总因果效应；第二阶段，分析具有显著因果效应的脂质组表型对91种炎症因子的影响；第三阶段，将脂质组作为暴露、炎症因子作为中介变量、CD作为结局，进行中介MR分析。此外，在所有步骤中均进行反向MR分析，以排除因果倒置的可能性（研究设计流程详见图1）。
1.2　数据来源
本研究使用的所有GWAS汇总数据均来源于OpenGWAS数据库，本研究无需通过额外的伦理委员会审批。脂质组学数据来源于GeneRISK队列，在脂质组学GWAS数据中，其通常遵循LIPID MAPS命名规范，其中斜杠前方的数字代表脂质骨架碳原子总数：双键数量。斜杠后面的数字代表脂肪酸侧链，同样遵循以上格式。中介以及结局数据集详细信息见表1。为了避免两样本MR分析中因样本重叠导致的弱工具偏倚和I类错误膨胀，本研究详细评估了暴露与结局数据集之间的重叠情况。虽然脂质组数据和结局数据均来自芬兰人群，但前者（N=7 174）仅占后者样本量（N=395 179）的约1.8%，远低于10%样本重叠率，其对因果推断的潜在偏倚影响可忽略。此外，中介数据与结局在人群构成上差异显著，无明显重叠。因此，本研究满足两样本MR设计的样本独立性假设。
1.3　工具变量筛选
本研究采用严格的质控标准筛选IVs：（1）设定全基因组显著性阈值为P<5e-08，筛选与暴露强相关的单核苷酸多态性（single nucleotide polymorphism，SNP）；（2）设定聚类窗口为10 000 kb，连锁不平衡系数r2<0.001，剔除存在连锁效应的SNPs；（3）计算每个SNP的F统计量（F=β2/SE2），仅保留F>10的SNP；（4）剔除等位基因频率（EAF）> 0.42的回文SNP，并协调暴露数据集与结局数据集的等位基因方向，剔除不兼容的变异位点。
1.4　数据分析
本研究基于R software（版本4.3.1）进行统计分析，主要调用“TwoSampleMR”（版本0.4.3）及“MendelianRandomization”数据包完成。采用IVW作为评估因果效应的主要模型，辅以MR-Egger回归、加权中位数法（Weighted Median）、简单模式（Simple Mode）和加权模式（Weighted Mode）进行补充分析。对于多重检验，采用Bonferroni法对P值进行校正。采用MR-Egger回归的截距项评估是否存在水平多效性（P>0.05视为不存在）；使用MR-PRESSO方法检测并校正潜在的离群值。利用Cochran Q统计量评估的异质性，若P<0.05表明存在显著异质性。
采用两步法进行中介分析［8］。首先计算脂质组对炎症因子的因果效应（β1），其次计算炎症因子对CD的因果效应（β2）。中介效应计算为βindirect=β1×β2。直接效应则通过脂质组对CD的总效应（βdirect=βtotal-βindirect）减去间接效应得出。采用Delta法估算中介效应的95%置信区间，并计算中介效应占总效应的比例（Proportion=βindirect/βtotal）。
2　结果
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2.1　脂质组与CD的因果关联分析
本研究鉴定出19种脂质代谢物与CD发病风险存在潜在的因果关联（IVW结果见图2，异质性检验结果见表2）。这些脂质主要包括二酰甘油、甾醇酯、磷脂酰胆碱、醚型磷脂酰胆碱、溶酶磷脂酰胆碱等亚类。最终，本研究筛选出磷脂酰胆碱18:1/20:4（Phosphatidylcholine, PC 18:1/20:4，GCST90277313）作为与CD关联最强的暴露因素，并进行后续的中介分析。MR-Egger截距项P值>0.05，未发现明显的水平多效性偏差，MR-PRESSO结果进一步验证了结果的稳健性。
2.2　脂质组对炎症因子的调控作用
探究PC（18:1/20:4）发挥保护作用的潜在机制，本研究确定了14种受该脂质显著调控的下游炎症因子（详见图3和表3）：TNF相关凋亡诱导配体（TNF-Related Apoptosis-Inducing Ligand, TRAIL）、C-X-C基序趋化因子9（C-X-C Motif Chemokine Ligand 9, CXCL9）、制瘤素M（Oncostatin M, OSM）、Delta和Notch样表皮生长因子相关受体（Delta and Notch-like Epidermal Growth Factor-related Receptor, DNER）、干细胞因子（Stem Cell Factor, SCF）、β-神经生长因子（Beta-Nerve Growth Factor, Beta-NGF）、T细胞表面糖蛋白CD6（Cluster of Differentiation 6, CD6）、基质金属蛋白酶-1（Matrix Metalloproteinase-1, MMP-1）、Fms相关酪氨酸激酶3配体（Fms-related Tyrosine Kinase 3 Ligand, Flt3L）、尿激酶型纤溶酶原激活物（Urokinase-type Plasminogen Activator, uPA）、血管内皮生长因子A（Vascular Endothelial Growth Factor A, VEGF-A）、C-X-C基序趋化因子6（CXCL6）、骨保护素（Osteoprotegerin, OPG）以及C-X-C基序趋化因子10（CXCL10）。
2.3　关键中介因素的鉴定
本研究分析了上述14种炎症因子对CD的影响，结果显示，仅有CD6和Fit3L与CD存在因果关联（见图4、表4）。通过将“脂质→炎症因子”与“炎症因子→CD”的两步分析结果进行交叉比对，发现 CD6同时满足中介路径：既显著受上游PC（18:1/20:4）调控，又能显著影响下游CD的发病风险。
2.4　因果方向验证排除反向因果偏移
为排除反向因果偏倚，本研究以CD为暴露、PC （18:1/20:4）为结局进行了反向MR分析。IVW结果显示OR=0.977, 95%CI：0.927～1.029，P=0.379，表明CD疾病状态不会反向导致该脂质水平的改变。
2.5　中介效应量化分析
基于“PC（18:1/20:4）→ CD6→CD”的中介模型，在暴露→中介路径（β1）中，PC（18:1/20:4）水平的升高显著降低了血浆CD6的水平（β1=-0.054，P<0.05）。而在中介→结局路径（β2）中，血浆CD6水平的降低显著减少了CD的发病风险（β2=0.197，P<0.05）。因此，经由CD6介导的间接效应值βindirect为-0.010，与总因果效应的（βtotal=-0.140）向一致，提示存在部分中介趋势，效应占比约为6.9%。然而，该间接路径的统计学显著性不足（Z值=-0.849，P=0.396，95%CI：-0.032～0.013）。虽然正式的中介效应检验未达统计学显著水平，这可能与样本量限制导致的统计效力不足有关，但两步法的显著结果提示脂质代谢异常通过调节CD6表达进而影响CD风险可能是一条具有生物学合理性的潜在致病通路。
3　讨论
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近年来，脂质组学在CD病理生理中的关键角色日益凸显，特定脂质代谢物被认为直接参与了肠道黏膜屏障的维护及免疫信号的调控［5,9］。本研究利用两样本MR分析，为磷脂酰胆碱（PC 18:1/20:4）作为CD发病的潜在保护因素提供了进一步的遗传学证据，这一结论与近期研究结果一致［10-11］。本研究初步揭示了T细胞表面糖蛋白CD6可能参与了该脂质的免疫调节过程，为理解“脂质代谢—免疫应答”在CD中作用提供了新视角。
在本研究筛选出的19种相关脂质中，特定结构的PC亚型显示出显著的CD保护效应，这一结果得到了近期多项独立MR研究的支持。Long等人［11］发现，甘油磷酸胆碱作为PC的主要代谢骨架，与CD风险呈显著负相关；而Ling等人［10］也鉴定出特定的磷脂亚型（如：1-stearoyl-2-arachidonoyl-GPI）具有保护效应，并强调了不同脂质亚型作用的异质性，这些研究提示胆碱能脂质代谢的稳态对于维持肠道健康至关重要。PC作为肠道黏液层和上皮细胞膜的主要磷脂成分，其在维持肠道疏水屏障功能中起着决定性作用［12］。然而，上述研究主要侧重于代谢组学的广泛筛选，对于脂质如何具体调控免疫系统从而影响疾病的机制仍缺乏。本研究引入了91种炎症因子进行中介分析，发现遗传性PC水平升高可能通过增强肠道黏膜屏障的完整性来抵御CD风险。研究表明， CD患者常伴有结肠黏液层PC含量的显著减少，这直接导致了屏障通透性增加和细菌移位［13］。此外，PC还具有明确的抗炎特性，补充PC能够重塑肠道菌群结构，并显著抑制促炎因子的表达，同时上调抗炎因子IL-10的水平［14-15］。Ben-Ami等人［16］进一步发现，PC可通过抑制IL-1β和Th17反应有效缓解实验性结肠炎的病理损伤。这些证据与本研究的遗传学发现高度一致，支持外源性或内源性PC水平的提升可能成为CD潜在的治疗策略。
为了揭示PC发挥保护作用的具体免疫路径， MR分析显示血浆CD6水平的升高是CD发病的独立风险因素，这与既往的免疫学研究相符［17-18］。虽然本研究针对“PC （18:1/20:4） → CD6→CD”之间的中介效应检验在统计学上未达到显著性，但这并不排除其生物学意义。CD6是表达于T淋巴细胞表面的重要共刺激分子，它通过与配体CD166结合，增强T细胞与抗原提呈细胞的黏附，促进T细胞的活化增殖［19］。活动性IBD患者炎症黏膜中CD6 mRNA表达显著上调，且与Th1/Th17型免疫反应的强度呈正相关［20］。因此，CD6过表达导致的T细胞过度激活可能是肠道炎症的重要驱动。此外，本研究发现PC（18:1/20:4）对CD6水平的负向调控作用。PC作为膜脂的主要成分，其脂肪酸链的饱和度可改变细胞膜的流动性和微结构域，进而干扰膜表面蛋白CD6的分布及信号转导效率［21］；此外，脂质代谢产物可能通过影响转录后修饰或溶酶体自噬途径调节CD6的降解［22］。因此，现有结果为“PC通过抑制CD6介导的T细胞过度活化从而保护CD”这一假说提供了初步线索，这可能是区别于单纯屏障修复功能的另一重要机制。
中介分析表明，PC可能通过下降CD6的水平来发挥CD保护作用。尽管本研究通过两步法观察到PC显著抑制CD6，且CD6显著增加CD风险，但在统计学上尚未达到显著水平（P=0.396）。这提示本研究需谨慎解读CD6的角色，这很可能归因于当前的GWAS汇总数据样本量限制了对微小间接效应的统计效力，导致出现了假阴性结果。此外，PC对CD的保护作用可能主要通过其他机制实现，而CD6途径可能仅是多重保护机制中的一环，未来需要更大样本量的研究及体内实验来确证这一信号通路的具体贡献度。
然而，本研究也存在一定的局限性。首先，由于遗传数据主要来自欧洲人群，本研究结论推广至亚洲或其他族裔人群需谨慎。其次，虽然MR分析提示了因果方向，但无法完全排除基因的多效性影响，尽管本研究的敏感性分析未发现显著偏差。再者，中介分析通常需要比主效应分析更大的样本量，本研究中介效应的不显著可能反映了当前数据的统计效力不足，而非生物学关联的缺失。最后，基于GWAS数据的分析无法揭示暴露与结局之间的非线性关系，也无法根据患者的年龄或疾病亚型进行分层探讨。未来的研究应结合多组学数据与功能实验，进一步解析“脂质-免疫”互作的具体分子机制。
4　结论
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本研究通过两样本MR揭示了血浆PC 18:1/20:4水平升高与CD发病风险降低之间存在稳健的潜在因果关联。该脂质能显著下调CD6的水平，而CD6的遗传升高则是CD的独立危险因素。虽然CD6作为单一介质的统计学检验未达到显著水平，但“脂质抑制CD6”与“CD6促进CD”这两个独立显著的路径提示，CD6可能是PC发挥免疫保护作用的潜在下游靶点之一。本研究不仅为脂质代谢在CD中的保护作用提供了进一步的遗传学证据，也为未来从脂质-免疫交互作用角度开发新的干预策略提供了线索。
基金
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  • 2025年学科人才建设费(XH40204-20250471)
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排序方式：
[1]
Torres J, Mehandru S, Colombel JF, et al. Crohn’s disease［J］. Lancet, 2017, 389(10080): 1741-1755.
[2]
Safarpour AR, Mehrabi M, Keshtkar A, et al. Systematic review and meta-analysis of the incidence and prevalence and 30-year trend of inflammatory bowel diseases in Asia: a study protocol［J］. BMJ Open, 2019, 9(11): e031854.
[3]
Li N, Shi RH. Updated review on immune factors in pathogenesis of Crohn’s disease［J］. World Journal of Gastroenterology, 2018, 24(1): 15-22.
[4]
Parada venegas D, De la Fuente MK, Landskron G, et al. Short chain fatty acids (SCFAs)-Mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases［J］. Frontiers in Immunology, 2019, 10: 277.
[5]
Sappati biyyani RSR, Putka BS, Mullen KD. Dyslipidemia and lipoprotein profiles in patients with inflammatory bowel disease［J］. Journal of Clinical Lipidology, 2010, 4(6): 478-482.
[6]
Koutroumpakis E, Ramos-Rivers C, Regueiro M, et al. Association between Long-Term lipid profiles and disease severity in a large cohort of patients with inflammatory bowel disease［J］. Digestive Diseases and Sciences, 2016, 61(3): 865-871.
[7]
Skrivankova VW, Richmond RC, Woolf BAR, et al. Strengthening the reporting of observational studies in epidemiology using mendelian randomization: the STROBE-MR statement［J］. the Journal of the American Medical Association, 2021, 326(16): 1614-1621.
[8]
Carter AR, Sanderson E, Hammerton G, et al. Mendelian randomisation for mediation analysis: current methods and challenges for implementation［J］. European Journal of Epidemiology, 2021, 36(5): 465-478.
[9]
Wang B, Rong X, Duerr MA, et al. Intestinal phospholipid remodeling is required for Dietary-Lipid uptake and survival on a High-Fat Diet［J］. Cell Metabolism, 2016, 23(3): 492-504.
[10]
Ling K, Zhang S, Jin L, et al. Blood metabolomic and Crohn’s disease: A Mendelian randomization study［J］. Medicine, 2025, 104(22): e42684.
[11]
Long XQ, Zhang YY, Liu MZ, et al. Causality of genetically determined blood metabolites on inflammatory bowel disease: a two-sample Mendelian randomization study［J］. Scientific Reports, 2024, 14(1): 16361.
[12]
Zheng WJ, Kollmeyer J, Symolon H, et al. Ceramides and other bioactive sphingolipid backbones in health and disease: Lipidomic analysis, metabolism and roles in membrane structure, dynamics, signaling and autophagy［J］. BBA-Biomembranes, 2006, 1758(12): 1864-1884.
[13]
Stremmel W, Ehehalt R, Staffer S, et al. Mucosal protection by phosphatidylcholine［J］. Digestive Diseases, 2012, 30(Suppl 3): 85-91.
[14]
Tan W, Zhang QJ, Dong ZJ, et al. Phosphatidylcholine ameliorates LPS-Induced systemic inflammation and cognitive impairments via mediating the Gut-Brain axis balance［J］. Journal of Agricultural and Food Chemistry, 2020, 68(50): 14884-14895.
[15]
Sanchez-Lopez E, Zhong ZY, Stubelius A, et al. Choline uptake and metabolism modulate macrophage IL-1β and IL-18 production［J］. Cell Metabolism, 2019, 29(6): 1350-1362.e7.
[16]
Ben-Ami shor D, Bashi T, Lachnish J, et al. Phosphorylcholine-tuftsin compoundprevents development of dextransulfate-sodium-salt induced murine colitis: implications for the treatment of human inflammatory bowel disease［J］. Journal of Autoimmunity, 2015, 56: 111-117.
[17]
Yin LL, Zhu Y, Kong F, et al. Causal association of plasma lipidome with inflammatory bowel diseases and mediating role of circulating inflammatory proteins: a mendelian randomization study［J］. Food Science & Nutrition, 2025, 13(9): e70916.
[18]
Tian Y, Wang F, Chen L, et al. Identifying novel inflammatory protein biomarkers and drug targets of inflammatory bowel disease by integrating mendelian randomization, bioinformatics, and druggability analysis［J］. International Archives of Allergy and Immunology, 2025, 186(10): 993-1008.
[19]
Jostins L, Ripke S, Weersma RK, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease［J］. Nature, 2012, 491(7422): 119-124.
[20]
Bughani U, Saha A, Kuriakose A, et al. T cell activation and differentiation is modulated by a CD6 domain 1 antibody Itolizumab［J］. PLOS One, 2017, 12(7): e0180088.
[21]
Sarrias MR, Farnós M, Mota R, et al. CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock［J］. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104(28): 11724-11729.
[22]
Smart CJ, Heatley RV, Trejdosiewicz LK. Expression of CD6 and the UCHL1-defined CD45 (p180) antigen by human colonic T lymphocytes［J］. Immunology, 1989, 66(1): 90-95.
2026年第53卷第12期
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doi: 10.20043/j.cnki.MPM.202601080
  • 接收时间：2026-01-06
  • 首发时间：2026-09-28
  • 出版时间：2026-06-25
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  • 收稿日期：2026-01-06
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2025年学科人才建设费(XH40204-20250471)
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    1.上海中医药大学附属龙华医院重症医学科，上海 200032
    2.上海中医药大学附属龙华医院脾胃病科

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2种不同金属材料的力学参数
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Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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