Independent and joint effects of genomic and exposomic loads for schizophrenia on psychotic experiences in adolescents of European ancestry
Year: 2025
Type: article
Abstract: This study aimed to assess the independent and joint associations of genomic and exposomic liabilities for schizophrenia with distressing psychotic experiences (PEs) and their persistence in early adolescence. The Adolescent Brain and Cognitive Development Study data from children with European ancestry were used (N = 5122). The primary outcome was past-month distressing PEs at the 3-year follow-up. Secondary outcomes were distressing PEs at varying cutoffs of persistence. Multilevel logistic regression models were used to test the associations of binary modes (>75th percentile) of polygenic risk score for schizophrenia (PRS-SCZ75) and exposome score for schizophrenia (ES-SCZ75) on the outcomes. Relative excess risk due to interaction (RERI) calculation indicated additive interaction. When analyzed independently, PRS-SCZ75 was not significantly associated with past-month distressing PEs but with lifetime (OR 1.29 [95% CI 1.08, 1.53]) and repeating distressing PEs ≥2 waves (OR 1.34 [95% CI 1.08, 1.65]); whereas, ES-SCZ75 was consistently associated with all outcomes, with increasing strength of association as a function of PEs persistence (one wave: OR 2.77 [95% CI 2.31, 3.31]; two waves: OR 3.16 [95% CI 2.54, 3.93]; three waves: OR 3.93 [95% CI 2.86, 5.40]; four waves: OR 3.65 [95% CI 2.34, 5.70]). When considered jointly, ES-SCZ75 and PRS-SCZ75 did not additively interact to predict past-month distressing PEs but showed significant additive interactions for lifetime (RERI = 1.26 [95%CI 0.14, 2.38]) and repeating distressing PEs ≥2 waves (RERI = 1.79 [95%CI 0.35, 3.23]). Genomic and exposomic liabilities for schizophrenia were independently and jointly associated with distressing PEs and their persistence in early adolescence.
Source: Schizophrenia
Institutions: University of Campania "Luigi Vanvitelli", Mahidol University, Ramathibodi Hospital, Maastricht University Medical Centre, King's College London, Utrecht University, University Medical Center Utrecht, Children's Hospital of Philadelphia, University of Pennsylvania Health System, University of Pennsylvania, Yale University, Maastricht University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,890
Funders: European Commission, ZonMw, National Institutes of Health, HORIZON EUROPE Framework Programme, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Institute of Mental Health, National Institute on Drug Abuse, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1020259976, G1058358382, G1378336923, G1436251778, G1510635755, G1569016918, G1586463187, Gene Environment interactions in Mental health trajectories of Youth, G2195549334, G2271121847, G2288485289, G2420845640, G2703413578, G2735337927, G2988863959, G2998093352, G3305455594, G343603955, G3438786812, G3661589251, G3738900353, G3755973507, G4066048162, G455352099, G4944172205, G5081895789, G5139799579, G5674573307, G687916792, G6887863799, Identifying Contributions to the Genetic Correlation Between Alcohol Use Disorders and Schizophrenia, G7271102572, 7/7 Psychiatric Genomics Consortium: Finding actionable variation, G761082118, G7652160222, G771167098, G815084465, G8281824583, Mapping the Human Connectome During Typical Aging, G8762821959, G9000002075, G9000006386, G9000007764, G9000008241, G9000011430, G9000034221, G9000041532, G9000041706, G9000108491, G9000112882, G9000130670, G9000148679, G9000163168, G9000191571, G9000205938, G9000208187, G9000241459, G9000271431, 9/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U MICHIGAN, 8/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT CHLA, 6/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT OHSU, 2/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UMB, G923039674
OpenAlex ID: W4407820653