| Title: | Exposome-Wide Gene-By-Environment Interaction Study of Psychotic Experiences in the UK Biobank |
| Journal: | Biological Psychiatry Global Open Science |
| Published: | 10 Feb 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40206033/ |
| DOI: | https://doi.org/10.1016/j.bpsgos.2025.100460 |
Publication 15190
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Abstract
Background: A previous study successfully identified 148 of 23,098 exposures associated with any psychotic experiences (PEs) in the UK Biobank using an exposome-wide association study (XWAS). Furthermore, research has shown that the polygenic risk score for schizophrenia (PRS-SCZ) is associated with PEs. However, the interaction of these exposures with PRS-SCZ remains unknown.</p>
Method: To systematically investigate possible gene-by-environment interactions underlying PEs through data-driven agnostic analyses, we conducted 1) conditional XWAS adjusting for PRS-SCZ to estimate the main effects of the exposures and of PRS-SCZ, 2) exposome-wide interaction study (XWIS) to estimate multiplicative and additive interactions between PRS-SCZ and exposures, and 3) correlation analyses between PRS-SCZ and exposures. The study included 148,502 participants from the UK Biobank.</p>
Results: In the conditional XWAS models, significant effects of PRS-SCZ and 148 exposures on PEs remained statistically significant. In the XWIS model, we found significant multiplicative (multiplicative scale, 1.23; 95% CI, 1.10-1.37; p = 4.0 × 10-4) and additive (relative excess risk due to interaction, 0.55; 95% CI, 0.32-0.77; synergy index, 0.22; 95% CI, 0.14-0.30; and attributable proportion, 1.59; 95% CI, 1.30-1.91; all ps < .05/148) interactions of PRS-SCZ and the variable serious medical conditions/disability with PEs. We additionally identified 6 additive gene-by-environment interactions for mental distress, help-/treatment-seeking behaviors (3 variables), sadness, and sleep problems. In the correlation test focused on 7 exposures that exhibited significant interactions with PRS-SCZ, nonsignificant or small (r < 0.04) gene-by-environment correlations were observed.</p>
Conclusions: These findings reveal evidence for gene-by-environment interactions underlying PEs and suggest that intertwined pathways of genetic vulnerability and exposures may contribute to psychosis risk.</p>
10 Authors
- Bochao Danae Lin
- Lotta-Katrin Pries
- Angelo Arias-Magnasco
- Boris Klingenberg
- David E.J. Linden
- Gabriëlla A.M. Blokland
- Dennis van der Meer
- Jurjen J. Luykx
- Bart P.F. Rutten
- Sinan Guloksuz
1 Application
| Application ID | Title |
|---|---|
| 55392 | Enhancing resilience in psychosis through within and between-family polygenic risk scoring, Gene x Gene interactions and gene-environment (GxE) prediction models (REGENESIS) |
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