{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:34:21Z","timestamp":1772138061736,"version":"3.50.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T00:00:00Z","timestamp":1686096000000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 research and innovation programme"},{"name":"Marie Sk\u0142odowska-Curie","award":["813533"],"award-info":[{"award-number":["813533"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>While the search for associations between genetic markers and complex traits has led to the discovery of tens of thousands of trait-related genetic variants, the vast majority of these only explain a small fraction of the observed phenotypic variation. One possible strategy to overcome this while leveraging biological prior is to aggregate the effects of several genetic markers and to test entire genes, pathways or (sub)networks of genes for association to a phenotype. The latter, network-based genome-wide association studies, in particular suffer from a vast search space and an inherent multiple testing problem. As a consequence, current approaches are either based on greedy feature selection, thereby risking that they miss relevant associations, or neglect doing a multiple testing correction, which can lead to an abundance of false positive findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>To address the shortcomings of current approaches of network-based genome-wide association studies, we propose networkGWAS, a computationally efficient and statistically sound approach to network-based genome-wide association studies using mixed models and neighborhood aggregation. It allows for population structure correction and for well-calibrated P-values, which are obtained through circular and degree-preserving network permutations. networkGWAS successfully detects known associations on diverse synthetic phenotypes, as well as known and novel genes in phenotypes from Saccharomycescerevisiae and Homo sapiens. It thereby enables the systematic combination of gene-based genome-wide association studies with biological network information.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>https:\/\/github.com\/BorgwardtLab\/networkGWAS.git.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btad370","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T21:03:45Z","timestamp":1686171825000},"source":"Crossref","is-referenced-by-count":7,"title":["<tt>networkGWAS<\/tt>\n                    : a network-based approach to discover genetic associations"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5999-2030","authenticated-orcid":false,"given":"Giulia","family":"Muzio","sequence":"first","affiliation":[{"name":"Machine Learning and Computational Biology Lab, Department of Biosystems Science and Engineering, ETH Zurich , 4058 Basel, Switzerland"},{"name":"Swiss Institute for Bioinformatics (SIB) , 1015 Lausanne, Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8999-9962","authenticated-orcid":false,"given":"Leslie","family":"O\u2019Bray","sequence":"additional","affiliation":[{"name":"Machine Learning and Computational Biology Lab, Department of Biosystems Science and Engineering, ETH Zurich , 4058 Basel, Switzerland"},{"name":"Swiss Institute for Bioinformatics (SIB) , 1015 Lausanne, Switzerland"}]},{"given":"Laetitia","family":"Meng-Papaxanthos","sequence":"additional","affiliation":[{"name":"Machine Learning and Computational Biology Lab, Department of Biosystems Science and Engineering, ETH Zurich , 4058 Basel, Switzerland"},{"name":"Swiss Institute for Bioinformatics (SIB) , 1015 Lausanne, Switzerland"},{"name":"Google Research, Brain Team , 8002 Z\u00fcrich, Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4096-566X","authenticated-orcid":false,"given":"Juliane","family":"Klatt","sequence":"additional","affiliation":[{"name":"Machine Learning and Computational Biology Lab, Department of Biosystems Science and Engineering, ETH Zurich , 4058 Basel, Switzerland"},{"name":"Swiss Institute for Bioinformatics (SIB) , 1015 Lausanne, Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3521-0599","authenticated-orcid":false,"given":"Krista","family":"Fischer","sequence":"additional","affiliation":[{"name":"Institute of Mathematics and Statistics, University of Tartu , 51009 Tartu, Estonia"},{"name":"Institute of Genomics, University of Tartu , 51010 Tartu, Estonia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7221-2393","authenticated-orcid":false,"given":"Karsten","family":"Borgwardt","sequence":"additional","affiliation":[{"name":"Machine Learning and Computational Biology Lab, Department of Biosystems Science and Engineering, ETH 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