{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T05:29:00Z","timestamp":1749187740837,"version":"3.37.3"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:00:00Z","timestamp":1637884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01-GM122078"],"award-info":[{"award-number":["R01-GM122078"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R21-CA209848"],"award-info":[{"award-number":["R21-CA209848"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["U01-DA045300"],"award-info":[{"award-number":["U01-DA045300"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["P30-AR072582","R01-AR071947"],"award-info":[{"award-number":["P30-AR072582","R01-AR071947"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,27]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Motivation<\/jats:title><jats:p>In spite of great success of genome-wide association studies (GWAS), multiple challenges still remain. First, complex traits are often associated with many single nucleotide polymorphisms (SNPs), each with small or moderate effect sizes. Second, our understanding of the functional mechanisms through which genetic variants are associated with complex traits is still limited. To address these challenges, we propose GPA-Tree and it simultaneously implements association mapping and identifies key combinations of functional annotations related to risk-associated SNPs by combining a decision tree algorithm with a hierarchical modeling framework.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>First, we implemented simulation studies to evaluate the proposed GPA-Tree method and compared its performance with existing statistical approaches. The results indicate that GPA-Tree outperforms existing statistical approaches in detecting risk-associated SNPs and identifying the true combinations of functional annotations with high accuracy. Second, we applied GPA-Tree to a systemic lupus erythematosus (SLE) GWAS and functional annotation data including GenoSkyline and GenoSkylinePlus. The results from GPA-Tree highlight the dysregulation of blood immune cells, including but not limited to primary B, memory helper T, regulatory T, neutrophils and CD8+ memory T cells in SLE. These results demonstrate that GPA-Tree can be a powerful tool that improves association mapping while facilitating understanding of the underlying genetic architecture of complex traits and potential mechanisms linking risk-associated SNPs with complex traits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>The GPATree software is available at https:\/\/dongjunchung.github.io\/GPATree\/.<\/jats:p><\/jats:sec><jats:sec><jats:title>Supplementary information<\/jats:title><jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btab802","type":"journal-article","created":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T12:17:00Z","timestamp":1637669820000},"page":"1067-1074","source":"Crossref","is-referenced-by-count":5,"title":["GPA-Tree: statistical approach for functional-annotation-tree-guided prioritization of GWAS results"],"prefix":"10.1093","volume":"38","author":[{"given":"Aastha","family":"Khatiwada","sequence":"first","affiliation":[{"name":"Department of Public Health Sciences, Medical University of South Carolina , Charleston, SC 29425, USA"},{"name":"Division of Biostatistics and Bioinformatics, National Jewish Health , Denver, CO 80206, USA"}]},{"given":"Bethany J","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Medical University of South Carolina , Charleston, SC 29425, USA"}]},{"given":"Ayse Selen","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, The Ohio State University , Columbus, OH 43210, USA"}]},{"given":"Paula S","family":"Ramos","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Medical University of South Carolina , Charleston, SC 29425, USA"},{"name":"Department of Medicine, Medical University of South Carolina , Charleston, SC 29425, USA"}]},{"given":"Maciej","family":"Pietrzak","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, The Ohio State University , Columbus, OH 43210, USA"}]},{"given":"Andrew","family":"Lawson","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Medical University of South Carolina , Charleston, SC 29425, USA"}]},{"given":"Kelly J","family":"Hunt","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Medical University of South Carolina , Charleston, SC 29425, USA"}]},{"given":"Hang J","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Statistics and Data Science, University of Cincinnati , Cincinnati, OH 45221, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8072-5671","authenticated-orcid":false,"given":"Dongjun","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, The Ohio State University , Columbus, OH 43210, USA"}]}],"member":"286","published-online":{"date-parts":[[2021,11,26]]},"reference":[{"key":"2023033004315015600_","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/art.20745","article-title":"Increase in activated CD8+ T lymphocytes expressing perforin and granzyme B correlates with disease activity in patients with systemic lupus erythematosus","volume":"52","author":"Blanco","year":"2005","journal-title":"Arthritis Rheumatism Off. 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