{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:34:12Z","timestamp":1772138052850,"version":"3.50.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"Supplement_1","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS100178"],"award-info":[{"award-number":["R01NS100178"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["639.072.715"],"award-info":[{"award-number":["639.072.715"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dutch Organization for Scientific Research"},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"name":"etherlands CardioVascular Research Initiative of the Netherlands Heart Foundation","award":["CVON 2011\/B019"],"award-info":[{"award-number":["CVON 2011\/B019"]}]},{"name":"etherlands CardioVascular Research Initiative of the Netherlands Heart Foundation","award":["CVON 2017-20"],"award-info":[{"award-number":["CVON 2017-20"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Pleiotropic SNPs are associated with multiple traits. Such SNPs can help pinpoint biological processes with an effect on multiple traits or point to a shared etiology between traits. We present PolarMorphism, a new method for the identification of pleiotropic SNPs from genome-wide association studies (GWAS) summary statistics. PolarMorphism can be readily applied to more than two traits or whole trait domains. PolarMorphism makes use of the fact that trait-specific SNP effect sizes can be seen as Cartesian coordinates and can thus be converted to polar coordinates r (distance from the origin) and theta (angle with the Cartesian x-axis, in the case of two traits). r describes the overall effect of a SNP, while theta describes the extent to which a SNP is shared. r and theta are used to determine the significance of SNP sharedness, resulting in a P-value per SNP that can be used for further analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We apply PolarMorphism to a large collection of publicly available GWAS summary statistics enabling the construction of a pleiotropy network that shows the extent to which traits share SNPs. We show how PolarMorphism can be used to gain insight into relationships between traits and trait domains and contrast it with genetic correlation. Furthermore, pathway analysis of the newly discovered pleiotropic SNPs demonstrates that analysis of more than two traits simultaneously yields more biologically relevant results than the combined results of pairwise analysis of the same traits. Finally, we show that PolarMorphism is more efficient and more powerful than previously published methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>code: https:\/\/github.com\/UMCUGenetics\/PolarMorphism, results: 10.5281\/zenodo.5844193.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btac228","type":"journal-article","created":{"date-parts":[[2022,4,14]],"date-time":"2022-04-14T07:10:15Z","timestamp":1649920215000},"page":"i212-i219","source":"Crossref","is-referenced-by-count":12,"title":["PolarMorphism enables discovery of shared genetic variants across multiple traits from GWAS summary statistics"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7067-1406","authenticated-orcid":false,"given":"Joanna","family":"von Berg","sequence":"first","affiliation":[{"name":"Center for Molecular Medicine, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"},{"name":"Oncode Institute, 3521 AL Utrecht, The Netherlands"}]},{"given":"Michelle","family":"ten Dam","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6888-1404","authenticated-orcid":false,"given":"Sander W","family":"van der Laan","sequence":"additional","affiliation":[{"name":"Central Diagnostics Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0828-3477","authenticated-orcid":false,"given":"Jeroen","family":"de Ridder","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"},{"name":"Oncode Institute, 3521 AL Utrecht, The Netherlands"}]}],"member":"286","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"2023041407525782100_","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.1161\/STROKEAHA.107.490896","article-title":"A computerized algorithm for etiologic classification of ischemic stroke: the causative classification of stroke system","volume":"38","author":"Ay","year":"2007","journal-title":"Stroke"},{"key":"2023041407525782100_","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/ng.3211","article-title":"LD score regression distinguishes confounding from polygenicity in genome-wide association studies","volume":"47","author":"Bulik-Sullivan","year":"2015","journal-title":"Nat. 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