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Genetic variants can provide useful complementary information for structure learning. Recently, Mendelian randomization (MR) studies have provided abundant marginal causal relationships of traits. Here, we propose a causal network pruning algorithm MRSL (MR-based structure learning algorithm) based on these marginal causal relationships. MRSL combines the graph theory with multivariable MR to learn the conditional causal structure using only genome-wide association analyses (GWAS) summary statistics. Specifically, MRSL utilizes topological sorting to improve the precision of structure learning. It proposes MR-separation instead of d-separation and three candidates of sufficient separating set for MR-separation. The results of simulations revealed that MRSL had up to 2-fold higher F1 score and 100 times faster computing time than other eight competitive methods. Furthermore, we applied MRSL to 26 biomarkers and 44 International Classification of Diseases 10 (ICD10)-defined diseases using GWAS summary data from UK Biobank. The results cover most of the expected causal links that have biological interpretations and several new links supported by clinical case reports or previous observational literatures.<\/jats:p>","DOI":"10.1093\/bib\/bbae086","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T07:02:47Z","timestamp":1710486167000},"source":"Crossref","is-referenced-by-count":4,"title":["MRSL: a causal network pruning algorithm based on GWAS summary data"],"prefix":"10.1093","volume":"25","author":[{"given":"Lei","family":"Hou","sequence":"first","affiliation":[{"name":"Beijing International Center for Mathematical Research, Peking University , Beijing , People\u2019s Republic of China , 100871"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Geng","sequence":"additional","affiliation":[{"name":"School of Mathematics and Statistics, Beijing Technology and Business University , Beijing , People\u2019s Republic of China , 100048"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongshang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics , School of Public Health, Cheeloo College of Medicine, , Jinan , People\u2019s Republic of China , 250000"},{"name":"Shandong University , School of Public Health, Cheeloo College of Medicine, , Jinan , People\u2019s Republic of China , 250000"},{"name":"Institute for Medical Dataology , Cheeloo College of Medicine, , Jinan , People\u2019s Republic of China , 250000"},{"name":"Shandong University , Cheeloo College of Medicine, , Jinan , People\u2019s Republic of China , 250000"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Michigan , Ann Arbor , 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Medicine, , Jinan , People\u2019s Republic of China , 250000"},{"name":"Institute for Medical Dataology , Cheeloo College of Medicine, , Jinan , People\u2019s Republic of China , 250000"},{"name":"Shandong University , Cheeloo College of Medicine, , Jinan , People\u2019s Republic of China , 250000"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0378-7956","authenticated-orcid":false,"given":"Fuzhong","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics , School of Public Health, Cheeloo College of Medicine, , Jinan , People\u2019s Republic of China , 250000"},{"name":"Shandong University , School of Public Health, Cheeloo College of Medicine, , Jinan , People\u2019s Republic of China , 250000"},{"name":"Institute for Medical Dataology , Cheeloo College of Medicine, , Jinan , People\u2019s Republic of China , 250000"},{"name":"Shandong University , Cheeloo College of Medicine, , Jinan , People\u2019s Republic of China , 250000"},{"name":"Qilu Hospital , Cheeloo College of Medicine, , Jinan , People's Republic of China , 250000"},{"name":"Shandong University , Cheeloo College of Medicine, , Jinan , People's Republic of China , 250000"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,14]]},"reference":[{"key":"2024031506414105400_ref1","doi-asserted-by":"crossref","DOI":"10.1017\/CBO9780511803161","volume-title":"Causality: Models, Reasoning and Inference","author":"Pearl","year":"2009"},{"key":"2024031506414105400_ref2","doi-asserted-by":"crossref","DOI":"10.7551\/mitpress\/1754.001.0001","volume-title":"Causation, Prediction, and Search","author":"Spirtes","year":"2001","edition":"2nd"},{"key":"2024031506414105400_ref3","first-page":"292","article-title":"Bayesian network prior: network analysis of biological data using external 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