Department of Complex Trait Genetics, Centre for Neurogenomics and Cognitive Research, VU University, Amsterdam, The Netherlands.
Department of Child and Adolescent Psychology and Psychiatry, section Complex Trait Genetics, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
Transl Psychiatry. 2021 Mar 22;11(1):180. doi: 10.1038/s41398-021-01288-9.
Gene-environment interactions (GxE) are often suggested to play an important role in the aetiology of psychiatric phenotypes, yet so far, only a handful of genome-wide environment interaction studies (GWEIS) of psychiatric phenotypes have been conducted. Representing the most comprehensive effort of its kind to date, we used data from the UK Biobank to perform a series of GWEIS for neuroticism across 25 broadly conceptualised environmental risk factors (trauma, social support, drug use, physical health). We investigated interactions on the level of SNPs, genes, and gene-sets, and computed interaction-based polygenic risk scores (PRS) to predict neuroticism in an independent sample subset (N = 10,000). We found that the predictive ability of the interaction-based PRSs did not significantly improve beyond that of a traditional PRS based on SNP main effects from GWAS, but detected one variant and two gene-sets showing significant interaction signal after correction for the number of analysed environments. This study illustrates the possibilities and limitations of a comprehensive GWEIS in currently available sample sizes.
基因-环境相互作用（GxE）被认为在精神表型的发病机制中起着重要作用，但迄今为止，仅进行了少数几项精神表型的全基因组环境相互作用研究（GWEIS）。本研究是迄今为止此类研究中最全面的一次，使用来自英国生物库的数据，针对神经质这一广泛概念化的 25 种环境风险因素（创伤、社会支持、药物使用、身体健康）进行了一系列 GWEIS 研究。我们在 SNP、基因和基因集水平上研究了相互作用，并计算了基于相互作用的多基因风险评分（PRS），以在一个独立的样本子集（N=10000）中预测神经质。我们发现，基于 SNP 主效应的传统 PRS 的预测能力并没有显著提高，但是在对分析环境数量进行校正后，检测到一个变体和两个基因集显示出显著的相互作用信号。本研究说明了在目前可用的样本量下，全面 GWEIS 的可能性和局限性。
