TY - UNPB
T1 - Independent and joint effects of genomic and exposomic loads for schizophrenia on distressing and persisting psychotic experiences in adolescence
AU - Vincenzo, Matteo Di
AU - Prachason, Thanavadee
AU - Sampogna, Gaia
AU - Arias-Magnasco, Angelo
AU - Danae Lin, Bochao
AU - Pries, Lotta-Katrin
AU - van Os, Jim
AU - Rutten, Bart P F
AU - Barzilay, Ran
AU - Fiorillo, Andrea
AU - Guloksuz, Sinan
PY - 2024/11/11
Y1 - 2024/11/11
N2 - To assess the longitudinal associations of genomic and exposomic liabilities for schizophrenia, both independently and jointly, 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=5,122). The primary outcome was past-month distressing PEs at 3-year follow-up. Secondary outcomes were lifetime distressing PEs defined at varying cutoffs of persistence (from = 1-4 waves). Multilevel logistic regression models were used to test the independent and joint associations of the binary modes (risk-category defined as above 75th percentile) of polygenic risk score for schizophrenia (PRS-SCZ ) and exposome score for schizophrenia (ES-SCZ ) on the outcomes. The relative excess risk due to interaction (RERI) was determined using the delta method to indicate departure additive interaction. PRS-SCZ was statistically significantly associated with lifetime distressing PEs (= 1 wave) (OR 1.29 [95% CI 1.08, 1.53]) and repeating distressing PEs = 2 waves (OR 1.34 [95% CI 1.08, 1.65]) but not with past-month distressing PEs or repeating distressing PEs at a higher cutoff of persistence. ES-SCZ was consistently associated with past-month and repeating distressing PEs at all cutoffs, 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]). There was evidence for additive interaction between ES-SCZ and PRS-SCZ for lifetime distressing PEs (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, as well as their persistence in early adolescence.
AB - To assess the longitudinal associations of genomic and exposomic liabilities for schizophrenia, both independently and jointly, 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=5,122). The primary outcome was past-month distressing PEs at 3-year follow-up. Secondary outcomes were lifetime distressing PEs defined at varying cutoffs of persistence (from = 1-4 waves). Multilevel logistic regression models were used to test the independent and joint associations of the binary modes (risk-category defined as above 75th percentile) of polygenic risk score for schizophrenia (PRS-SCZ ) and exposome score for schizophrenia (ES-SCZ ) on the outcomes. The relative excess risk due to interaction (RERI) was determined using the delta method to indicate departure additive interaction. PRS-SCZ was statistically significantly associated with lifetime distressing PEs (= 1 wave) (OR 1.29 [95% CI 1.08, 1.53]) and repeating distressing PEs = 2 waves (OR 1.34 [95% CI 1.08, 1.65]) but not with past-month distressing PEs or repeating distressing PEs at a higher cutoff of persistence. ES-SCZ was consistently associated with past-month and repeating distressing PEs at all cutoffs, 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]). There was evidence for additive interaction between ES-SCZ and PRS-SCZ for lifetime distressing PEs (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, as well as their persistence in early adolescence.
KW - adolescence
KW - environment
KW - gene-environment interaction
KW - polygenic risk score
KW - psychotic experiences
KW - schizophrenia
U2 - 10.1101/2024.11.11.24316985
DO - 10.1101/2024.11.11.24316985
M3 - Preprint
BT - Independent and joint effects of genomic and exposomic loads for schizophrenia on distressing and persisting psychotic experiences in adolescence
ER -