Evidence mapPaperPMID 41845536Full record

ArticleHuman genomics2026

Cross-trait genomic and sequential analyses of multiple omics datasets identified shared genetic components for the gut-eye axis.

Yuelan Gao, Jianming Xu, Jun Yu, Yuyao Wang, Yuzhou Zhang, Ka Wai Kam, Mary Ho, Alvin L Young, Chi Pui Pang, Clement C Tham and 2 more

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Article in Human genomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Yuelan GaoDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong, China.
Jianming XuDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong, China.
Jun YuDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong, China.
Yuyao WangDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong, China.
Yuzhou ZhangDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong, China.
Ka Wai KamDepartment of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong, China.
Mary HoDepartment of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong, China.
Alvin L YoungDepartment of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong, China.
Chi Pui PangDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong, China.
Clement C ThamDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong, China.
Jason C YamDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong, China. yamcheuksing@cuhk.edu.hk.
Li Jia ChenDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong, China. lijia_chen@cuhk.edu.hk.

Funding

The Chinese University of Hong Kong Direct Grant Medical Panel 4054762the General Research Fund, Hong Kong 14100724the Health and Medical Research Fund Hong Kong 10210236the Health and Medical Research Fund Hong Kong 11220136the HKAM-HKGI Research Excellence Grants in Genomic Medicine 6907056the Research Matching Grant (RMG) by the Hong Kong Government 8601668
6 · The paper itself

Abstract

backgroundThe gut–eye axis (GEA) has been proposed as a framework for understanding comorbidity between gastrointestinal and ocular diseases. This study aimed to investigate their shared genetic architecture, pleiotropy, and putative biological pathways potentially influenced by environmental exposures and gut microbiota.

methodsThis study integrated large-scale genome-wide association study summary data on five gastrointestinal and eight ocular diseases to assess genetic correlations and genetic overlap. Pleiotropic variants were identified, followed by functional and tissue-specific analyses. Gene–environment (G×E) interactions were evaluated using UK Biobank data. Mendelian randomization (MR) and mediation analyses were adopted to assess statistically inferred associations and potential mediating relationships involving gut microbiota.

resultsExtensive genetic correlations were identified between 40 trait pairs. In total, 366 pleiotropic loci were identified, with 21 loci showing evidence of colocalized shared signals. Notably, 2p21, 4q24, 19q13.32 and 5p15.31 were colocalized across 2 trait pairs, highlighting them as recurrent pleiotropic loci of potential interest. Of the 603 genes associated with pleiotropic variants, 261 recurred across two or more trait pairs. These genes were enriched in immune and inflammatory pathways and included well-known loci such as HLA-B and RBFOX1. Twenty-six pleiotropic variants interacted with 16 modifiable exposures (e.g., diet, mental health, BMI, smoking, physical activity), suggesting that G×E interactions may contribute to gut–eye comorbidity risk. Bidirectional MR identified 11 genetically predicted associations, while mediation analysis suggested a potential statistical association involving the polyamine biosynthesis pathway in the relationship between gastroesophageal reflux disease and diabetic retinopathy.

conclusionsThis study characterizes shared genetic and environmental architecture across GEA-related disorders and highlights putative contributions from immune-related pathways and gut microbiota to disease comorbidity. Our findings provide a hypothesis-generating framework for future replication and experimental validation.

Indexed as

Eye DiseasesGastrointestinal DiseasesGastrointestinal MicrobiomeGene-Environment InteractionGenetic PleiotropyGenetic Predisposition to DiseaseGenome-Wide Association StudyGenomicsHumansMendelian Randomization AnalysisPolymorphism, Single NucleotideQuantitative Trait LociGene–environmentGenetic pleiotropyGut–eye axisGut microbiota

Identifiers

PMID41845536
PMCPMC13107603

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.