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Finally, using liability-threshold modeling, we quantify the relative magnitudes of genetic perturbations, microenvironmental effects, and stochasticity, establishing a strategy for dissecting the origins of phenotypic variability.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2619147123","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T16:24:01Z","timestamp":1786551841000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["A quantitative model of a phenotypically variable genetic defect"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9661-9112","authenticated-orcid":false,"given":"Alison G.","family":"Simpkins","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00hx57361","id-type":"ROR","asserted-by":"publisher"}],"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University","place":["Princeton"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2698-041X","authenticated-orcid":false,"given":"Dominic J.","family":"Skinner","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00sekdz59","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Computational Biology, Flatiron Institute","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brox","family":"Felix","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00hx57361","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Biology, Princeton University","place":["Princeton"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3895-0584","authenticated-orcid":false,"given":"Robert A.","family":"Marmion","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00hx57361","id-type":"ROR","asserted-by":"publisher"}],"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University","place":["Princeton"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8180-4179","authenticated-orcid":false,"given":"Jodi","family":"Schottenfeld-Roames","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00hx57361","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Biology, Princeton University","place":["Princeton"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9152-9334","authenticated-orcid":false,"given":"Stanislav Y.","family":"Shvartsman","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00hx57361","id-type":"ROR","asserted-by":"publisher"}],"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University","place":["Princeton"]},{"id":[{"id":"https:\/\/ror.org\/00sekdz59","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Computational Biology, Flatiron Institute","place":["New York"]},{"id":[{"id":"https:\/\/ror.org\/00hx57361","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Biology, Princeton University","place":["Princeton"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","unstructured":"J. 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