The retina, an anatomical extension of the brain, forms physiological connections with the visual cortex of the brain. Although retinal structures offer a unique opportunity to assess brain disorders, their relationship to brain structure and function is not well understood. In this study, we conducted a systematic cross-organ genetic architecture analysis of eye-brain connections using retinal and brain imaging endophenotypes. We identified novel phenotypic and genetic links between retinal imaging biomarkers and brain structure and function measures from multimodal magnetic resonance imaging (MRI), with many associations involving the primary visual cortex and visual pathways. Retinal imaging biomarkers shared genetic influences with brain diseases and complex traits in 65 genomic regions, with 18 showing genetic overlap with brain MRI traits. Mendelian randomization suggests bidirectional genetic causal links between retinal structures and neurological and neuropsychiatric disorders, such as Alzheimer’s disease. Overall, our findings reveal the genetic basis for eye-brain connections, suggesting that retinal images can help uncover genetic risk factors for brain disorders and disease-related changes in intracranial structure and function.

视网膜是大脑的解剖延伸，与大脑的视觉皮层形成生理联系。尽管视网膜结构提供了评估大脑疾病的独特机会，但它们与大脑结构和功能的关系尚不清楚。在这项研究中，我们利用视网膜和大脑成像内表型对眼脑连接进行了系统的跨器官遗传结构分析。我们通过多模态磁共振成像（MRI）确定了视网膜成像生物标志物与大脑结构和功能测量之间的新表型和遗传联系，其中许多关联涉及初级视觉皮层和视觉通路。视网膜成像生物标志物与 65 个基因组区域中的脑部疾病和复杂性状具有共同的遗传影响，其中 18 个显示出与脑部 MRI 性状的遗传重叠。孟德尔随机化表明视网膜结构与神经和神经精神疾病（例如阿尔茨海默病）之间存在双向遗传因果关系。总的来说，我们的研究结果揭示了眼脑连接的遗传基础，表明视网膜图像可以帮助揭示大脑疾病的遗传风险因素以及与疾病相关的颅内结构和功能变化。