Biomaterial Database

Eye-brain connections revealed by multimodal retinal and brain imaging genetics in the UK Biobank. 2023

Bingxin Zhao, and Yujue Li, and Zirui Fan, and Zhenyi Wu, and Juan Shu, and Xiaochen Yang, and Yilin Yang, and Xifeng Wang, and Bingxuan Li, and Xiyao Wang, and Carlos Copana, and Yue Yang, and Jinjie Lin, and Yun Li, and Jason L Stein, and Joan M O'Brien, and Tengfei Li, and Hongtu Zhu

Department of Statistics and Data Science, University of Pennsylvania, Philadelphia, PA 19104, USA.

As an anatomical extension of the brain, the retina of the eye is synaptically connected to the visual cortex, establishing physiological connections between the eye and the brain. Despite the unique opportunity retinal structures offer for assessing brain disorders, less is known about their relationship to brain structure and function. Here we present a systematic cross-organ genetic architecture analysis of eye-brain connections using retina and brain imaging endophenotypes. Novel phenotypic and genetic links were identified between retinal imaging biomarkers and brain structure and function measures derived from multimodal magnetic resonance imaging (MRI), many of which were involved in the visual pathways, including the primary visual cortex. In 65 genomic regions, retinal imaging biomarkers shared genetic influences with brain diseases and complex traits, 18 showing more genetic overlaps with brain MRI traits. Mendelian randomization suggests that retinal structures have bidirectional genetic causal links with neurological and neuropsychiatric disorders, such as Alzheimer's disease. Overall, cross-organ imaging genetics reveals a genetic basis for eye-brain connections, suggesting that the retinal images can elucidate genetic risk factors for brain disorders and disease-related changes in intracranial structure and function.