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It identifies 75,243 significant pleiotropic SNPs and derives 2,527 risk loci and 4,272 candidate pleiotropic genes using FUMA and MAGMA, including broadly pleiotropic genes such as TERT, POU5F1B, and FANCA.",{"@graph":14,"@context":71},[15,34,54],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/large-scale-pleiotropic-analysis-across-cancers-reveals-shared-genetic-mechanisms-and-identifies-novel-functional-genes-case-study/346138/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":48,"encodingFormat":47,"isAccessibleForFree":49,"interactionStatistic":50},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/large-scale-pleiotropic-analysis-across-cancers-reveals-shared-genetic-mechanisms-and-identifies-novel-functional-genes-case-study/346138.png","ImageObject",300,407,{"name":42,"@type":43},"Valentina","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-09-22",true,{"@type":51,"interactionType":52,"userInteractionCount":4},"InteractionCounter",{"@type":53},"ViewAction",{"@type":55,"mainEntity":56},"FAQPage",[57,63,67],{"name":58,"@type":59,"acceptedAnswer":60},"What data and scope were used for the pleiotropic analysis across cancers?","Question",{"text":61,"@type":62},"The analysis used genome-wide association study summary statistics for 37 cancer types with a total sample size of N = 433,836.","Answer",{"name":64,"@type":59,"acceptedAnswer":65},"How many pleiotropic results and candidate genes were identified?",{"text":66,"@type":62},"Pairwise analysis across 372 cancer pairs found 75,243 significant pleiotropic SNPs. The study identified 2,527 pleiotropic risk loci and 4,272 candidate pleiotropic genes using FUMA and MAGMA.",{"name":68,"@type":59,"acceptedAnswer":69},"What functional insights and pathways were highlighted by the study?",{"text":70,"@type":62},"Pathway enrichment emphasized roles related to pigment synthesis, metabolism, and apoptosis in skin-related cancers, and across cancers highlighted apoptosis, chromatin structure, and intermediate filaments.","https://schema.org",{"og:url":32,"og:type":73,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":75,"canonical":32},"index,follow",{"doc_id":77,"site_id":7},346138,1790060195,{"code":4,"msg":80,"data":81},"success",[82,86,90,94,99,104,109,113,118,121,125],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":83,"show_sort_weight":84,"slug":85},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":87,"show_sort_weight":88,"slug":89},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":91,"show_sort_weight":92,"slug":93},"Exam",70,"exam",{"id":95,"doc_module":4,"doc_module_name":25,"category_name":96,"show_sort_weight":97,"slug":98},5,"Comic",60,"comic",{"id":100,"doc_module":4,"doc_module_name":25,"category_name":101,"show_sort_weight":102,"slug":103},6,"Technology",50,"technology",{"id":105,"doc_module":4,"doc_module_name":25,"category_name":106,"show_sort_weight":107,"slug":108},7,"Healthcare",40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":111,"slug":112},8,30,"research-report",{"id":114,"doc_module":4,"doc_module_name":25,"category_name":115,"show_sort_weight":116,"slug":117},9,"Religion & Spirituality",20,"religion-spirituality",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":119,"show_sort_weight":116,"slug":120},"World Cup","world-cup",{"id":122,"doc_module":4,"doc_module_name":25,"category_name":123,"show_sort_weight":122,"slug":124},10,"Lifestyle","lifestyle",{"id":126,"doc_module":4,"doc_module_name":25,"category_name":127,"show_sort_weight":95,"slug":128},19,"General","general",{"code":4,"msg":80,"data":130},{"doc_id":77,"user_id":131,"nickname":42,"user_avatar":132,"doc_module":4,"category_id":110,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":4,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":138,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":78,"read_time":143},13056703020460,"https://ap-avatar.wpscdn.com/avatar/be000253dac470eee5d?_k=1778207105932848923","Briefings in Bioinformatics, 2026, 27, bbag479 [https://doi.org/10.1093/bib/bbag479](https://doi.org/10.1093/bib/bbag479)  \nPublished: 7 September 2026  \nCase Study  \nLarge-scale pleiotropic analysis across cancers reveals shared genetic mechanisms and identifies novel functional genes  \nXiaohong Wu1 ,‡, Yuqing Yan1 ,‡, Wen Cao1 , Tian Wu1 , Jiaxing He1 , Dongyang Wang1 , Jing Gong1 , 2 , *, Xiaohui Niu 1 , *  \n1 Hubei Hongshan Laboratory, College of Informatics, Huazhong Agricultural University, No. 1 Shizishan Street, Hongshan District, Wuhan 430070, Hubei, China  \n2 College of Biomedicine and Health, Huazhong Agricultural University, No. 1 Shizishan Street, Hongshan District, Wuhan 430070, Hubei, China  \n*Corresponding authors. Xiaohui Niu, Department of Bioinformatics, Huazhong Agricultural University, Wuhan 430070, China. E-mail: [niuxiaoh@mail.hzau.edu.cn](niuxiaoh@mail.hzau.edu.cn); Jing Gong, Department of Bioinformatics,  \nHuazhong Agricultural University, Wuhan 430070, China. E-mail: [gong.jing@mail.hzau.edu.cn](gong.jing@mail.hzau.edu.cn)  \n‡Xiaohong Wu and Yuqing Yan contributed equally to this work.  \n\n| Abstract\u003Cbr>Pleiotropic genetic loci have been increasingly reported in cancer, and identifying genetic variants with pleiotropic associations can reveal shared biological pathways influencing multiple cancers. Using summary statistics from genome-wide association studies for 37 cancer types (N = 433 836), we identified extensive genome-wide and local genetic correlations among cancers. Through pairwise pleiotropic analysis, we identified 75 243 significant pleiotropic single nucleotide polymorphisms (SNPs) across 372 cancer pairs, among which 3472 were lead SNPs with potential regulatory functions. Using FUMA and MAGMA, we identified 2527 pleiotropic risk loci and 4272 candidate pleiotropic genes. Notably, genes such as TERT (5p15.33), POU5F1B (8q24.21), and FANCA (16q24.3) exhibited widespread pleiotropy across multiple cancer types. Pathway enrichment analysis highlighted the critical roles of pigment synthesis, metabolism, and apoptosis in skinrelated cancers, while cross-cancer enrichment analysis emphasized pathways related to apoptosis, chromatin structure, and intermediate filaments. We also identified 33 novel functional genes harboring previously unreported cancer risk variants. Drug-gene interaction analysis revealed several repositionable FDA-approved drugs. Importantly, drug sensitivity assays demonstrated that bosutinib and cobimetinib exhibited promising therapeutic potential in breast cancer cell lines. Finally, we developed the PleioCancer database ([https://gonglab.hzau](https://gonglab.hzau). [edu.cn/PleioCancer/](edu.cn/PleioCancer/)), providing a comprehensive resource for cancer pleiotropy research. These findings have important implications for carcinogenesis cancer, prevention and treatment.\u003Cbr>Keywords pleiotropy, cancer genetics, GWAS, drug repositioning, precision oncology\u003Cbr>Introduction\u003Cbr>independent pleiotropic variants across 18 cancers in two European |  |\n| --- | --- |\n| Cancer remains significant global health burden, with complex and | cohorts, with the associated genes significantly enriched in 36 path- |\n| heterogeneous pathogenesis. Despite advances in early detection, | ways [3]. However, pleiotropy remains underexplored in several rarer |\n| diagnosis, and treatment, the incidence and mortality rates of cancer | cancer types. |\n| remain high [1] . Genome-wide association studies (GWAS) have | Pleiotropic analysis may also provide new targets and strategies |\n| identified thousands of genetic variants associated with cancer | for cancer prevention and treatment. Studies suggest that genetic |\n| risk, however, these variants account for only a fraction of genetic | loci failing to reach significance in single-cancer GWAS may become |\n| susceptibility [2] . Additionally, observed genetic correlations among | significant in joint analyses across multiple cancers [5], thus avoiding","cbCaidJIt0iVWoZV","https://ap.wps.com/l/cbCaidJIt0iVWoZV","pdf",3110481,18,"English","# Abstract\n# Introduction","[{\"question\":\"What data and scope were used for the pleiotropic analysis across cancers?\",\"answer\":\"The analysis used genome-wide association study summary statistics for 37 cancer types with a total sample size of N = 433,836.\"},{\"question\":\"How many pleiotropic results and candidate genes were identified?\",\"answer\":\"Pairwise analysis across 372 cancer pairs found 75,243 significant pleiotropic SNPs. The study identified 2,527 pleiotropic risk loci and 4,272 candidate pleiotropic genes using FUMA and MAGMA.\"},{\"question\":\"What functional insights and pathways were highlighted by the study?\",\"answer\":\"Pathway enrichment emphasized roles related to pigment synthesis, metabolism, and apoptosis in skin-related cancers, and across cancers highlighted apoptosis, chromatin structure, and intermediate filaments.\"}]","Large-scale pleiotropic analysis across cancers reveals shared genetic mechanisms and identifies novel functional genes - Case Study | PDF",45]