Lin, Bochao Danae, Pries, Lotta-Katrin, Arias-Magnasco, Angelo, Klingenberg, Boris, Linden, David E.J.  ORCID: https://orcid.org/0000-0002-5638-9292, Blokland, Gabriëlla A.M., van der Meer, Dennis, Luykx, Jurjen J., Rutten, Bart P.F. and Guloksuz, Sinan
2025.
Exposome-wide gene-by-environment interaction study of psychotic experiences in the UK Biobank.
Biological Society Global Open Science
5
(3)
, 100460.
10.1016/j.bpsgos.2025.100460
|
Preview |
PDF
- Published Version
Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (217kB) | Preview |
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. 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. 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. 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.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Medicine |
| Publisher: | Elsevier |
| ISSN: | 2667-1743 |
| Date of First Compliant Deposit: | 10 March 2025 |
| Date of Acceptance: | 29 January 2025 |
| Last Modified: | 16 Apr 2025 10:00 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/176686 |
Actions (repository staff only)
 |
Edit Item |
Altmetric
Altmetric