Skip to main contentNews & ViewsPublished: 05 June 2025Human geneticsJulian Stamp ORCID: orcid.org/0000-0003-3014-62491 &Lorin Crawford ORCID: orcid.org/0000-0003-0178-82422 Nature Cardiovascular Research (2025)Cite this articleMetrics detailsSubjectsCardiac hypertrophyCardiovascular geneticsGene expression profilingMachine learningStem-cell biotechnologyFinding phenotypic variance that results from gene interactions (epistasis) has been a longstanding challenge in human genetics. The combination of a new machine learning framework with functional genomics now provides evidence that cardiac hypertrophy is regulated by non-additive genetic interactions.This is a preview of subscription content, access via your institutionAccess optionsSubscribe to this journalReceive 12 digital issues and online access to articles118,99 € per yearonly 9,92 € per issueLearn moreBuy this articlePurchase on SpringerLinkInstant access to full article PDFBuy nowPrices may be subject to local taxes which are calculated during checkoutFig. 1: Multi-stage machine-learning pipeline for discovering and validating epistatic effects.ReferencesZeng, L. et al. Cardiovasc. Res. 118, 1088–1102 (2022).Article CAS PubMed Google Scholar Li, Y. et al. J. Am. Heart Assoc. 9, e014146 (2020).Article PubMed PubMed Central Google Scholar Meyer, H. V. et al. Nature 584, 589–594 (2020).Article CAS PubMed PubMed Central Google Scholar O’Sullivan, J. W. et al. Circulation 146, e93–e118 (2022).Article PubMed PubMed Central Google Scholar Hivert, V. et al. Am. J. Hum. Genet. 108, 786–798 (2021).Article CAS PubMed PubMed Central Google Scholar Wang, Q. et al. Nat. Cardiovasc. Res. https://doi.org/10.1038/s44161-025-00656-8 (2025).Article PubMed PubMed Central Google Scholar Sudlow, C. et al. PLoS Med. 12, e1001779 (2015).Article PubMed PubMed Central Google Scholar Bai, W. et al. J. Cardiovasc. Magn. Reson. 20, 65 (2018).Article PubMed PubMed Central Google Scholar Basu, S., Kumbier, K., Brown, J. B. & Yu, B. Proc. Natl Acad. Sci. USA 115, 1943–1948 (2018).Article CAS PubMed PubMed Central Google Scholar Purcell, S. et al. Am. J. Hum. Genet. 81, 559–575 (2007).Article CAS PubMed PubMed Central Google Scholar Loh, P.-R. et al. Nat. Genet. 47, 284–290 (2015).Article CAS PubMed PubMed Central Google Scholar Pattillo Smith, S. et al. eLife 13, e90459 (2024).Article PubMed PubMed Central Google Scholar Hemani, G. et al. Nature 596, E1–E3 (2021).Article CAS PubMed Google Scholar Download referencesAuthor informationAuthors and AffiliationsCenter for Computational Molecular Biology, Brown University, Providence, RI, USAJulian StampMicrosoft Research, Cambridge, MA, USALorin CrawfordAuthorsJulian StampView author publicationsYou can also search for this author inPubMed Google ScholarLorin CrawfordView author publicationsYou can also search for this author inPubMed Google ScholarCorresponding authorsCorrespondence to Julian Stamp or Lorin Crawford.Ethics declarationsRights and permissionsReprints and permissionsAbout this article