{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:19:26Z","timestamp":1787894366965,"version":"build-2784847793"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genetic Epidemiology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Complex disorders such as depression and alcohol use involve numerous genetic variants, and implicated loci continue to grow with sample size. This proliferation hampers interpretability, as the mechanisms by which so many variants jointly contribute to pathophysiology remain unclear. In contrast, classical Mendelian diseases arise from a single causal locus and are easier to interpret. We thus introduce\n                    <jats:italic>Mendelianization<\/jats:italic>\n                    \u2014an algorithm distinct from Mendelian randomization\u2014that learns weighted combinations of outcomes so that each aggregated phenotype concentrates association at one locus. We prove that this locus is causal under four structural assumptions natural to genetic data. The method handles partial sample overlap, provides calibrated hypothesis tests, maps coefficients to interpretable scales, and quantifies the degree of Mendelianism using summary \u2010statistics alone. In experiments, Mendelianization enhances statistical power to detect Mendelian symptom profiles even in heterogeneous disorders like major depression, generalized anxiety, and alcohol use disorder. An R implementation is available at\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/github.com\/ericstrobl\/Mendelianization\">github.com\/ericstrobl\/Mendelianization<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1002\/gepi.70053","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T12:05:56Z","timestamp":1786709156000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mendelianization: Concentrating Polygenic Signal Into a Single Causal Locus"],"prefix":"10.1002","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9894-9694","authenticated-orcid":false,"given":"Eric V.","family":"Strobl","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2022.01.002"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2022.04.003"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0579-z"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw052"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-021-01059-6"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.12.024"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2014.10.010"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41562-019-0566-x"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2014.92"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-025-02335-7"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41562-024-02073-6"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781119482260"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2010.120"},{"issue":"1","key":"e_1_2_13_16_1","first-page":"117","article-title":"Alcohol\u2010Related Behaviors in a Mouse Model Containing the Human Gckr Snp rs1260326 (P446l)","volume":"48","author":"Mehrhoff E. 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