[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-437922-105":59,"doc-detail-437922-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","genetic-evidence-supports-primary-biliary-cholangitis-as-a-risk-factor-for-lacunar-stroke","Genetic evidence supports primary biliary cholangitis as a risk factor for lacunar stroke","","Genetic evidence is used to evaluate whether primary biliary cholangitis (PBC) causally increases lacunar stroke risk, a common cerebrovascular subtype. A two-sample Mendelian randomization framework applies genetic instruments for PBC from large-scale genome-wide association studies and tests effects on lacunar stroke in independent datasets. Discovery analysis shows increased risk (OR 1.0635, 95% CI 1.0224–1.1063, p 0.0022), with consistent replication across updated PBC datasets. Sensitivity analyses show no significant pleiotropy and support robustness. Overall findings indicate PBC as a causal risk factor, motivating early prevention strategies and further targeted research.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/genetic-evidence-supports-primary-biliary-cholangitis-as-a-risk-factor-for-lacunar-stroke/437922/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/genetic-evidence-supports-primary-biliary-cholangitis-as-a-risk-factor-for-lacunar-stroke/437922.png","ImageObject",300,407,{"name":92,"@type":93},"Danger Angel","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-09","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What method was used to test whether PBC affects lacunar stroke risk?","Question",{"text":113,"@type":114},"The study used a two-sample Mendelian randomization (MR) approach, using genetic instruments for PBC and testing associations with lacunar stroke in independent datasets.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Did the genetic prediction of PBC increase the risk of lacunar stroke?",{"text":118,"@type":114},"Yes. In the discovery analysis, genetically predicted PBC was associated with an increased lacunar stroke risk (OR 1.0635, p=0.0022), and the result was replicated in updated datasets.",{"name":120,"@type":111,"acceptedAnswer":121},"What do the sensitivity analyses suggest about the robustness of the findings?",{"text":122,"@type":114},"Sensitivity analyses indicated no significant pleiotropy and confirmed the robustness of the causal inference.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},437922,1790866708,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":105,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},962090769052,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","iScience Article  \nGenetic evidence supports primary biliary cholangitis as a risk factor for lacunar stroke  \nGraphical abstract  \n\n| \u003Cbr>Genetic Evidence Supports Primary Biliary Cholangitis as a Risk Factor for Lacunar Stroke |  |  |\n| --- | --- | --- |\n| | | |\n|  | \u003Cbr>The second phase |  |\n\nHighlights  \n• PBC causally increases risk of lacunar stroke  \n• MR evidence is consistent across multiple GWAS  \n• No horizontal pleiotropy detected in analyses  \n• Supports early stroke prevention in PBC patients  \nAuthors  \nMengmeng Wang, Nan Zhang,  \nLing Zhang, Ning Zhang, Haichu Yu  \nCorrespondence  \n[drwmengmengno1@163.com](drwmengmengno1@163.com) (M.W.),  \n[zhangningqdfy@yeah.net](zhangningqdfy@yeah.net) (N.Z.),  \n[haichuyu@163.com](haichuyu@163.com) (H.Y.)  \nIn brief  \nHealth sciences  \nWang et al., 2025, iScience 28, 114240  \nDecember 19, 2025 © 2025 The Author(s) . Published by Elsevier Inc.  \n[https://doi.org/10.1016/j.isci.2025.114240](https://doi.org/10.1016/j.isci.2025.114240)  \nll  \niScience  \nll  \nOPEN ACCESS  \nArticle  \nGenetic evidence supports primary biliary cholangitis as a risk factor for lacunar stroke  \nMengmeng Wang,1,5,* Nan Zhang,2,5 Ling Zhang,3,5 Ning Zhang,1,* and Haichu Yu1,4,6,*  \n1Department of Cardiology, The Affiliated Hospital of Qingdao University, Qing Dao, Shandong, China  \n2Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China  \n3General Medicine Department, Heze Municipal Hospital, Heze, Shandong, China  \n4Institute of Cardiovascular Disease, Qingdao University, Qingdao 266001, Shandong, China  \n5These authors contributed equally  \n6Lead contact  \n*Correspondence: [drwmengmengno1@163.com](drwmengmengno1@163.com) (M.W.), [zhangningqdfy@yeah.net](zhangningqdfy@yeah.net) (N.Z.), [haichuyu@163.com](haichuyu@163.com) (H.Y.) [https://doi.org/10.1016/j.isci.2025.114240](https://doi.org/10.1016/j.isci.2025.114240)  \nSUMMARY  \nPrimary biliary cholangitis (PBC) is a chronic autoimmune liver disease, while lacunar stroke is a common cerebrovascular subtype. Understanding potential systemic vascular consequences of PBC is crucial for patient management. Using a two-sample Mendelian randomization (MR) approach, we investigated the causal effect of PBC on lacunar stroke risk. We utilized genetic instruments for PBC from large-scale genome-wide association studies and tested their association with lacunar stroke in independent datasets. In the discovery analysis, genetically predicted PBC was associated with an increased risk of lacunar stroke (odds ratio [OR] = 1.0635, 95% confidence interval [CI]: 1.0224–1.1063; p = 0.0022). This finding was consistently replicated using two updated PBC datasets (OR = 1.0671, p = 0.0014; OR = 1.0548, p = 0.0026) . Sensitivity analyses indicated no significant pleiotropy and confirmed result robustness. This genetic evidence suggests PBC is a causal risk factor for lacunar stroke, warranting further investigation and targeted prevention.  \nINTRODUCTION  \nPrimary biliary cholangitis (PBC) is a chronic disease characterized by the deterioration of small bile ducts within the liver, leading to inflammation around the portal areas, loss of bile ducts, impaired bile flow, and the development of biliary cirrhosis overtime.1 PBC is considered a model autoimmune illness due to the serological findings, evidence of antimitochondrial antibody (AMA), and the unique bile duct pathological alterations observed in the disease.2 PBC is most commonly diagnosed when regular laboratory tests show an increase in alkaline phosphatase. AMA, the serological marker of PBC, is found in approximately 95% of people with the disease yet occurs in less than 1% of healthy adults. High alkaline phosphatase levels along with the presence of AMA are sufficient to identify the condition.3 PBC is more commonly diagnosed in women, with a female to male ratio of roughly 10 to 1.4 The prevalence of PBC ranges from 1.91 to 40.20 per 100,000 people","cbCaiaiinfa8E60k","https://ap.wps.com/l/cbCaiaiinfa8E60k","pdf",6050117,"English","# Highlights\n## Summary\n# Introduction\n## Primary biliary cholangitis (PBC)\n## Stroke and lacunar stroke","[{\"question\":\"What method was used to test whether PBC affects lacunar stroke risk?\",\"answer\":\"The study used a two-sample Mendelian randomization (MR) approach, using genetic instruments for PBC and testing associations with lacunar stroke in independent datasets.\"},{\"question\":\"Did the genetic prediction of PBC increase the risk of lacunar stroke?\",\"answer\":\"Yes. In the discovery analysis, genetically predicted PBC was associated with an increased lacunar stroke risk (OR 1.0635, p=0.0022), and the result was replicated in updated datasets.\"},{\"question\":\"What do the sensitivity analyses suggest about the robustness of the findings?\",\"answer\":\"Sensitivity analyses indicated no significant pleiotropy and confirmed the robustness of the causal inference.\"}]","Genetic evidence supports primary biliary cholangitis as a risk factor for lacunar stroke | PDF",1790683517,28]