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

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; Hongtu Zhu

doi:10.1101/2023.02.16.23286035

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

medRxiv [Preprint]. 2023 Feb 17:2023.02.16.23286035. doi: 10.1101/2023.02.16.23286035.

Authors

Bingxin Zhao^{1

2}, Yujue Li², Zirui Fan¹, Zhenyi Wu², Juan Shu², Xiaochen Yang², Yilin Yang³, Xifeng Wang⁴, Bingxuan Li⁵, Xiyao Wang⁵, Carlos Copana², Yue Yang⁴, Jinjie Lin⁶, Yun Li^{4

7}, Jason L Stein^{7

8}, Joan M O'Brien^{9

10}, Tengfei Li^{11

12}, Hongtu Zhu^{4

7

13

14}

Affiliations

¹ Department of Statistics and Data Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
² Department of Statistics, Purdue University, West Lafayette, IN 47907, USA.
³ Department of Computer and Information Science and Electrical and Systems Engineering, School of Engineering & Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁴ Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁵ Department of Computer Science, Purdue University, West Lafayette, IN 47907, USA.
⁶ Yale School of Management, Yale University, New Haven, CT 06511, USA.
⁷ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁸ UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁹ Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.
¹⁰ Penn Medicine Center for Ophthalmic Genetics in Complex Diseases, PA, 19104, USA.
¹¹ Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
¹² Biomedical Research Imaging Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
¹³ Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
¹⁴ Department of Statistics and Operations Research, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Abstract

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.

Keywords: Brain MRI; Brain disorders; Fundus photography; GWAS; OCT; Retinal imaging; Transfer Learning; UK Biobank; Visual pathways.

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Preprint

Abstract

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