Eye-brain connections revealed by multimodal retinal and brain imaging genetics

Bingxin Zhao (), Yujue Li, Zirui Fan, Zhenyi Wu, Juan Shu, Xiaochen Yang, Yilin Yang, Xifeng Wang, Bingxuan Li, Xiyao Wang, Carlos Copana, Yue Yang, Jinjie Lin, Yun Li, Jason L. Stein, Joan M. O’Brien, Tengfei Li and Hongtu Zhu ()
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Bingxin Zhao: University of Pennsylvania
Yujue Li: Purdue University
Zirui Fan: University of Pennsylvania
Zhenyi Wu: Purdue University
Juan Shu: Purdue University
Xiaochen Yang: Purdue University
Yilin Yang: University of Pennsylvania
Xifeng Wang: University of North Carolina at Chapel Hill
Bingxuan Li: Purdue University
Xiyao Wang: Purdue University
Carlos Copana: Purdue University
Yue Yang: University of North Carolina at Chapel Hill
Jinjie Lin: Yale University
Yun Li: University of North Carolina at Chapel Hill
Jason L. Stein: University of North Carolina at Chapel Hill
Joan M. O’Brien: University of Pennsylvania
Tengfei Li: University of North Carolina at Chapel Hill
Hongtu Zhu: University of North Carolina at Chapel Hill

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-50309-w

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