[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-443915-105":59,"doc-detail-443915-en":130},{"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":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","archipelago-method-for-variant-set-association-test-statistics","Archipelago Method for Variant Set Association Test Statistics","","Variant set association tests (VSAT), especially those incorporating rare variants via variant collapse, are crucial in genetic studies. Unlike single-variant Manhattan plots, VSAT statistics have no inherent genomic coordinates, limiting visual interpretation. The Archipelago method assigns meaningful genomic coordinates to VSAT P values, enabling intuitive joint visualization of set-level and individual-variant effects. Validation across simulated and real datasets, from 504 to 490,640 UK Biobank participants, integrates single-variant GWAS with gene/protein pathway collapse workflows and supports clear communication and causal variant identification.",{"@graph":69,"@context":122},[70,84,105],{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/archipelago-method-for-variant-set-association-test-statistics/443915/",{"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/archipelago-method-for-variant-set-association-test-statistics/443915.png","ImageObject",300,407,{"name":92,"@type":93},"Taylor Morgan","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-01","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does the Archipelago method address in VSAT analysis?","Question",{"text":112,"@type":113},"VSAT P-values lack inherent genomic coordinates, making their visual interpretation difficult compared with single-variant Manhattan plots.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the Archipelago method enable visualization of VSAT results?",{"text":117,"@type":113},"It assigns a meaningful genomic coordinate to each VSAT P value based on the average of its constituent variants, allowing set-level and individual variant effects to be visualized together.",{"name":119,"@type":110,"acceptedAnswer":120},"What types of datasets and study designs were used to validate the method?",{"text":121,"@type":113},"The method was validated using three studies covering simulated and real datasets across small to biobank-scale cohorts, integrating single-variant GWAS with gene- and protein pathway-level rare-variant collapse results.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},443915,1790812906,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":39,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":46},1099523885336,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Genetic Epidemiology   \n RESEARCH ARTICLE   \nArchipelago Method for Variant Set Association Test Statistics  \nDylan Lawless1  | Ali Saadat2 | Mariam Ait Oumelloul2 | Luregn J. Schlapbach1 | Jacques Fellay2  \n1Department of Intensive Care and Neonatology, University Children's Hospital Zürich, University of Zürich, Zürich, Switzerland | 2GlobalHealth Institute, School of Life Sciences, ÉcolePolytechnique Fédérale de Lausanne, Lausanne, Switzerland  \nCorrespondence: Dylan Lawless ([Dylan.Lawless@kispi.uzh.ch](Dylan.Lawless@kispi.uzh.ch))  \nReceived: 10 May 2025 | Revised: 19 August 2025 | Accepted: 22 December 2025  \nFunding: The Swiss Personalized Health Network and the Strategic Focal Area 'Personalized Health and Related Technologies' of the ETH Domain (Swiss Federal Institutes of Technology), Grant/Award Number: NDS‐2021‐911; The Swiss Pediatric Sepsis Study received funding from the Swiss National Science Foundation, Grant/Award Number: 320030_ 201060/1  \nKeywords: Archipelago | combined | GWAS | RVAT | VSAT  \nABSTRACT  \nVariant set association tests (VSAT), especially those incorporating rare variants via variant collapse, are invaluable in genetic studies. However, unlike Manhattan plots for single‐variant tests, VSAT statistics lack intrinsic genomic coordinates, hindering visual interpretation. To overcome this, we developed the Archipelago method, which assigns a meaningful genomic coordinate to VSAT P values so that both set‐level and individual variant associations can be visualised together. This results in an intuitive and information rich illustration akin to an Archipelago of clustered islands, enhancing the understanding of both collective and individual impacts of variants. We conducted three validation studies spanning simulated and real datasets across small and biobank‐scale cohorts, from 504 individuals up to 490,640 UK Biobank participants. We integrated single‐variant genome‐ wide association studies (GWAS) with gene‐ and protein pathway‐level rare‐variant collapse. These studies included the 1KG GWAS cohort, the Pan‐UK Biobank GWAS with DeepRVAT WES gene‐level study, and the UKBB WGS gene‐level UTR collapsing PheWAS. The Archipelago plot is applicable in any genetic association study that uses variant collapse to evaluate both individual variants and variant sets, and its customisability facilitates clear communication of complex genetic data. By integrating at least two dimensions of genetic data into a single visualisation, VSAT results can be easily read and aid in identification of potential causal variants in variant sets such as protein pathways.  \n1 | Introduction  \nVariant set association tests (VSATs) are methods in which groups of variants are collapsed and analysed jointly to enhance an association signal. VSAT, particularly those incorporating rare variants (e.g. minor allele frequencies below 1%), have become indispensable in genetic association studies (Derkachet al. 2014; Lee et al. 2014; Larson et al. 2019; Povysil et al. 2019;  \nLi et al. 2022; Clarke and Holtkamp 2024) . Next‐generation sequencing has enabled the comprehensive detection of rare variants, thereby complementing traditional single‐variant tests (Nicolae 2016; The UK Biobank Whole‐Genome Sequencing Consortium et al. 2025) . While Manhattan plots effectively visualise single‐variant associations (Turner 2018), a comparable graphical representation for VSAT results has been lacking.  \n\n| GitHub repository: [https://github.com/DylanLawless/archipelago](https://github.com/DylanLawless/archipelago).\u003Cbr>CRAN submission: Archipelago Version 0.0.1.9000.\u003Cbr>Zenodo: [https://doi.org/10.5281/zenodo.16880622](https://doi.org/10.5281/zenodo.16880622) . |\n| --- |\n| This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.\u003Cbr>© 2026 The Author(s) . Genetic Epidemiology published by Wiley Periodica","cbCaibb9sIo41ZLd","https://ap.wps.com/l/cbCaibb9sIo41ZLd","pdf",2070903,"English","# Introduction\n## Background on VSAT and rare variant collapse\n## Need for genomic-coordinates visualization\n# The Archipelago Plot\n## Assigning genomic coordinates to VSAT P values\n## Joint visualization of set-level and individual effects\n# Validation Studies\n## Simulated and real datasets across cohort scales\n## Integration with single-variant GWAS and rare-variant collapse","[{\"question\":\"What problem does the Archipelago method address in VSAT analysis?\",\"answer\":\"VSAT P-values lack inherent genomic coordinates, making their visual interpretation difficult compared with single-variant Manhattan plots.\"},{\"question\":\"How does the Archipelago method enable visualization of VSAT results?\",\"answer\":\"It assigns a meaningful genomic coordinate to each VSAT P value based on the average of its constituent variants, allowing set-level and individual variant effects to be visualized together.\"},{\"question\":\"What types of datasets and study designs were used to validate the method?\",\"answer\":\"The method was validated using three studies covering simulated and real datasets across small to biobank-scale cohorts, integrating single-variant GWAS with gene- and protein pathway-level rare-variant collapse results.\"}]","Archipelago Method for Variant Set Association Test Statistics | PDF",1790706053]