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This study examined whether the interaction of SS\u2010related genetic markers with interview\u2010based dimensions of childhood adversity predicted longitudinal trajectories of low versus high SS. Participants were nonclinically\u2010ascertained young adults comprising normative and elevated scores on schizotypy. SS trajectories were defined in a previous report based on three prospective assessments (23.5, 25, 28 years\u2010old) of both retrospective (Perceived Stress Scale; PSS) and momentary (Experience Sampling Methodology; ESM) stress ratings. A total of <jats:italic>n<\/jats:italic>\u00a0=\u00a0177 and <jats:italic>n<\/jats:italic>\u00a0=\u00a0165 participants with PSS and ESM stress\u2010sensitivity trajectories, respectively, as well as genetic data, were included in the study. GxE effects between a SS Polygenic Risk Score (PRS\u2010SS) and a Genetic Risk Score of the Hypothalamic Pituitary Adrenal axis (GRS\u2010HPA) with childhood adversity dimensions (Intrafamilial Adversity, Threat and Deprivation) on SS trajectories were examined. Threat was the most consistent predictor of persistently high SS. PRS\u2010SS moderated the association of Threat with high\u2010PSS. GRS\u2010HPA moderated the effects of all adversity dimensions on high\u2010PSS. The interaction of PRS\u2010SS with Deprivation and GRS\u2010HPA with Intrafamilial Adversity predicted trajectories of momentary social stress, but the effects were driven by those with lower genetic susceptibility. Genetic\u2010HPA\u2010axis moderates the effects of all adversity dimensions on persistent SS trajectories, as well as PRS\u2010SS and Threat, particularly for retrospective stress measure. The findings highlight the complex interplay between GxE factors and suggest that PSS may better capture SS trait. Including biologically\u2010meaningful GRS indexing SS and adversity dimensions in future studies using comprehensive stress measures would enhance our knowledge on high SS susceptibility and its relationship with diverse psychopathological outcomes.<\/jats:p>","DOI":"10.1002\/smi.3499","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T12:56:09Z","timestamp":1731588969000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Interaction of Polygenic Susceptibility to Stress and Childhood Adversity Dimensions Predicts Longitudinal Trajectories of Stress\u2010Sensitivity"],"prefix":"10.1002","volume":"40","author":[{"given":"N.","family":"Barrantes\u2010Vidal","sequence":"first","affiliation":[{"name":"Departament de Psicologia Cl\u00ednica i de la Salut Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0901-7226","authenticated-orcid":false,"given":"A.","family":"Gizdic","sequence":"additional","affiliation":[{"name":"Departament de Psicologia Cl\u00ednica i de la Salut Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Torrecilla","sequence":"additional","affiliation":[{"name":"Departament de Psicologia Cl\u00ednica i de la Salut Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Mas\u2010Bermejo","sequence":"additional","affiliation":[{"name":"Facultat de Biologia Departament de Biologia Evolutiva, Ecologia i Ci\u00e8ncies Ambientals Secci\u00f3 de Zoologia i Antropologia Biol\u00f2gica Universitat de Barcelona  Barcelona Spain"},{"name":"Institut de Biomedicina de la Universitat de Barcelona (IBUB)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Sheinbaum","sequence":"additional","affiliation":[{"name":"Direcci\u00f3n de Investigaciones Epidemiol\u00f3gicas y Psicosociales Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz  M\u00e9xico City M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Papiol","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental Instituto de Salud Carlos III  Madrid Spain"},{"name":"Institute of Psychiatric Phenomics and Genomics (IPPG) University Hospital LMU Munich  Munich Germany"},{"name":"Department of Psychiatry and Psychotherapy University Hospital LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Lafit","sequence":"additional","affiliation":[{"name":"Department of Neurosciences KU Leuven  Leuven Belgium"},{"name":"Department of Psychology and Education Sciences KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Myin\u2010Germeys","sequence":"additional","affiliation":[{"name":"Department of Neurosciences KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Rosa","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental Instituto de Salud Carlos III  Madrid Spain"},{"name":"Facultat de Biologia Departament de Biologia Evolutiva, Ecologia i Ci\u00e8ncies Ambientals Secci\u00f3 de Zoologia i Antropologia Biol\u00f2gica Universitat de Barcelona  Barcelona Spain"},{"name":"Institut de Biomedicina de la Universitat de Barcelona (IBUB)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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