This study investigates the genetic and phenotypic connections between the retina and the brain using multimodal imaging data. The retina, an anatomical extension of the brain, forms physiological connections with the visual cortex. The study analyzed retinal imaging biomarkers and brain structure and function measures from magnetic resonance imaging (MRI) data, identifying novel links between retinal imaging and brain health. Key findings include: 1. **Phenotypic Associations**: Retinal imaging traits, such as retinal layer thickness and fundus image features, were associated with brain structural measures, including regional brain volumes, cortical thickness, and diffusion tensor imaging (DTI) parameters. These associations were observed in both healthy subjects and those with various brain disorders. 2. **Genetic Architecture**: Genetic analysis revealed significant overlaps between retinal imaging traits and brain MRI traits in 65 genomic regions. Many of these regions also showed genetic associations with eye and brain disorders, such as Alzheimer's disease, Parkinson's disease, and glaucoma. 3. **Mendelian Randomization**: Mendelian randomization studies suggested bidirectional genetic causal links between retinal structures and neurological and neuropsychiatric disorders, indicating that changes in retinal structure can influence brain health and vice versa. 4. **Predictive Power**: Combining retinal and brain imaging data improved the prediction of brain-related traits and diseases, highlighting the potential of multi-organ imaging for early detection and monitoring of neurological conditions. Overall, the study provides a comprehensive understanding of the genetic and phenotypic connections between the retina and the brain, suggesting that retinal imaging can serve as a valuable tool for diagnosing and managing brain disorders.This study investigates the genetic and phenotypic connections between the retina and the brain using multimodal imaging data. The retina, an anatomical extension of the brain, forms physiological connections with the visual cortex. The study analyzed retinal imaging biomarkers and brain structure and function measures from magnetic resonance imaging (MRI) data, identifying novel links between retinal imaging and brain health. Key findings include: 1. **Phenotypic Associations**: Retinal imaging traits, such as retinal layer thickness and fundus image features, were associated with brain structural measures, including regional brain volumes, cortical thickness, and diffusion tensor imaging (DTI) parameters. These associations were observed in both healthy subjects and those with various brain disorders. 2. **Genetic Architecture**: Genetic analysis revealed significant overlaps between retinal imaging traits and brain MRI traits in 65 genomic regions. Many of these regions also showed genetic associations with eye and brain disorders, such as Alzheimer's disease, Parkinson's disease, and glaucoma. 3. **Mendelian Randomization**: Mendelian randomization studies suggested bidirectional genetic causal links between retinal structures and neurological and neuropsychiatric disorders, indicating that changes in retinal structure can influence brain health and vice versa. 4. **Predictive Power**: Combining retinal and brain imaging data improved the prediction of brain-related traits and diseases, highlighting the potential of multi-organ imaging for early detection and monitoring of neurological conditions. Overall, the study provides a comprehensive understanding of the genetic and phenotypic connections between the retina and the brain, suggesting that retinal imaging can serve as a valuable tool for diagnosing and managing brain disorders.