Exposome-Wide Gene-By-Environment Interaction Study of Psychotic Experiences in the UK Biobank

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science Pub Date : 2025-02-10 DOI:10.1016/j.bpsgos.2025.100460

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

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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.

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.

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英国生物银行精神病经历的暴露范围基因-环境相互作用研究

之前的一项研究使用全暴露关联研究（XWAS）成功地确定了英国生物银行23,098次暴露中与任何精神病经历（pe）相关的148次暴露。此外，研究表明，精神分裂症的多基因风险评分（PRS-SCZ）与pe相关。然而，这些暴露与PRS-SCZ的相互作用仍然未知。方法通过数据驱动的不确定性分析，系统地研究pe可能的基因-环境相互作用，我们进行了1)条件XWAS调整PRS-SCZ来估计暴露和PRS-SCZ的主要影响，2)暴露范围相互作用研究（XWIS）来估计PRS-SCZ与暴露之间的乘法和加性相互作用，3)PRS-SCZ与暴露之间的相关性分析。这项研究包括来自英国生物银行的148,502名参与者。结果在条件XWAS模型中，PRS-SCZ和148暴露对pe的影响仍有统计学意义。在XWIS模型中，我们发现显著的乘法(乘法尺度，1.23；95% ci, 1.10-1.37；P = 4.0 × 10−4)和加性(相互作用导致的相对超额风险，0.55；95% ci, 0.32-0.77；协同指数，0.22；95% ci, 0.14-0.30；归属比例为1.59；95% ci, 1.30-1.91；所有ps <；.05/148) PRS-SCZ与pe的各种严重医疗状况/残疾的相互作用。此外，我们还确定了精神困扰、寻求帮助/治疗行为（3个变量）、悲伤和睡眠问题的6种基因与环境的相互作用。在相关检验中，重点关注与PRS-SCZ有显著相互作用的7种暴露，不显著或较小(r <；0.04)基因与环境相关。结论：这些发现为pe背后的基因-环境相互作用提供了证据，并表明遗传易感性和暴露的相互交织的途径可能导致精神病风险。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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