Genome‐Wide by Lifetime Environment Interaction Studies of Brain Imaging Phenotypes

作者：Sijia Wang, Meiyun Wang, Peng Zhang, Jingliang Cheng, Long Jiang Zhang, Wenzhen Zhu, Shijun Qiu, Zuojun Geng, Guangbin Cui, Yongqiang Yu, Weihua Liao, Xi‐Nian Zuo, Hui Zhang, Bo Gao, Xiaojun Xu, Tong Han, Zhenwei Yao, Quan Zhang, Feng Liu, Qiang Xu, Jiayuan Xu, Jilian Fu, Nana Liu, Yuan Ji, Jie Tang, Lining Guo, Mengge Liu, Xiaoxiao Xiao, Xiaoxuan Liu, Wei Li, Caihong Wang, Wei Wei, Dapeng Shi, Su Lui, Zhihan Yan, Feng Chen, Jing Zhang, Wen Shen, Yanwei Miao, Dawei Wang, Jia‐Hong Gao, Yunjun Yang, Kai Xu, Junfang Xian, Bing Zhang, Xiaochu Zhang, Zhaoxiang Ye, Le Yu, Wen Qin, Meng Liang, Chunshui Yu · 发表于：Advanced Science · 年份：2025 · DOI：10.1002/advs.202500852 · 被引用次数：2 · 研究领域：Health, Environment, Cognitive Aging、Functional Brain Connectivity Studies、Genetic Associations and Epidemiology

Brain structure and function show substantial individual differences, finely controlled by genes, environments, and their interactions. Despite the increasing knowledge about genetic and environmental main effects, gene-environment interaction effects on brain phenotypes remain elusive. This study investigates genome-wide by environment (41 exposures) interactions on 598 brain imaging phenotypes in 7084 healthy young adults. Both univariate and multivariate analyses identify 486 significant gene-environment interactions, scattered across the genome, exposome, and phenome. These interactions explain more variances of phenotypes than genetic and environmental main effects (100% of genetic and 96% of environmental main effects are non-significant). Variants with interactions are enriched in intronic and intergenic regions, comprising 79 regulatory variants and 145 associated with brain gene expression. Protein-protein interaction network analyses reveal distinct interaction networks for genes associated with air pollution (hubs: H4C6, SMARCA4, and RPS11) and urbanicity (hubs: CCND1, CALM3, and CDK2) exposures. Genes that interacted with air pollution exposures exhibit enrichment in pathways related to metal ion detoxification and homeostasis. For time-varying exposures, 144 interactions demonstrate sensitive periods, predominantly in childhood (ages 4-7) and adolescence (ages 12-15). These findings highlight the value of genome-wide by exposome-wide interaction studies, which ma...