Whole-genome sequencing identifies novel loci for keratoconus and facilitates risk stratification in a Han Chinese population Article Swipe
Yinghao Yao
,
Xingyong Li
,
Wu Lan
,
Jia Zhang
,
Yuanyuan Gui
,
Xiangyi Yu
,
Yang Zhou
,
Xuefei Li
,
xinyu liu
,
Shilai Xing
,
Gang An
,
Zhenlin Du
,
Hui Liu
,
Shasha Li
,
Xiaoguang Yu
,
Hua Chen
,
Jianzhong Su
,
Shihao Chen
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1186/s40662-024-00421-1
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1186/s40662-024-00421-1
Background Keratoconus (KC) is a prevalent corneal condition with a modest genetic basis. Recent studies have reported significant genetic associations in multi-ethnic cohorts. However, the situation in the Chinese population remains unknown. This study was conducted to identify novel genetic variants linked to KC and to evaluate the potential applicability of a polygenic risk model in the Han Chinese population. Methods A total of 830 individuals diagnosed with KC and 779 controls from a Chinese cohort were enrolled and genotyped by whole-genome sequencing (WGS). Common and rare variants were respectively subjected to single variant association analysis and gene-based burden analysis. Polygenic risk score (PRS) models were developed using top single-nucleotide polymorphisms (SNPs) identified from a multi-ethnic meta-analysis and then evaluated in the Chinese cohort. Results The characterization of germline variants entailed correction for population stratification and validation of the East Asian ancestry of the included samples via principal component analysis. For rare protein-truncating variants (PTVs) with minor allele frequency (MAF) < 5%, ZC3H11B emerged as the top prioritized gene, albeit failing to reach the significance threshold. We detected three common variants reaching genome-wide significance ( P ≤ 5 × 10 −8 ), all of which are novel to KC. Our study validated three well known predisposition loci, COL5A1 , EIF3A and FNDC3B . Additionally, a significant correlation of allelic effects was observed for suggestive SNPs between the largest multi-ethnic meta-genome-wide association study (GWAS) and our study. The PRS model, generated using top SNPs from the meta-GWAS, stratified individuals in the upper quartile, revealing up to a 2.16-fold increased risk for KC. Conclusions Our comprehensive WGS-based GWAS in a large Chinese cohort enhances the efficiency of array-based genetic studies, revealing novel genetic associations for KC and highlighting the potential for refining clinical decision-making and early prevention strategies.
Related Topics
Concepts
Genome-wide association study
Single-nucleotide polymorphism
Genetics
Biology
Genetic association
Population stratification
Population
SNP
Allele frequency
Allele
Genotype
Gene
Medicine
Environmental health
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1186/s40662-024-00421-1
- https://eandv.biomedcentral.com/counter/pdf/10.1186/s40662-024-00421-1
- OA Status
- diamond
- References
- 58
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4406086345
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4406086345Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1186/s40662-024-00421-1Digital Object Identifier
- Title
-
Whole-genome sequencing identifies novel loci for keratoconus and facilitates risk stratification in a Han Chinese populationWork title
- Type
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articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
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2025-01-06Full publication date if available
- Authors
-
Yinghao Yao, Xingyong Li, Wu Lan, Jia Zhang, Yuanyuan Gui, Xiangyi Yu, Yang Zhou, Xuefei Li, xinyu liu, Shilai Xing, Gang An, Zhenlin Du, Hui Liu, Shasha Li, Xiaoguang Yu, Hua Chen, Jianzhong Su, Shihao ChenList of authors in order
- Landing page
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https://doi.org/10.1186/s40662-024-00421-1Publisher landing page
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https://eandv.biomedcentral.com/counter/pdf/10.1186/s40662-024-00421-1Direct link to full text PDF
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YesWhether a free full text is available
- OA status
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diamondOpen access status per OpenAlex
- OA URL
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https://eandv.biomedcentral.com/counter/pdf/10.1186/s40662-024-00421-1Direct OA link when available
- Concepts
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Genome-wide association study, Single-nucleotide polymorphism, Genetics, Biology, Genetic association, Population stratification, Population, SNP, Allele frequency, Allele, Genotype, Gene, Medicine, Environmental healthTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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58Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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