Epidemiologic association and shared genetic architecture between cataract and hearing difficulties among middle-aged and older adults
Abstract Age-related cataract and hearing difficulties are major sensory disorders that often co-exist in the global-wide elderly and have a tangible influence on the quality of life. However, the epidemiologic association between cataract and hearing difficulties remains unexplored, while little is...
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BMC
2024-04-01
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| Series: | Human Genomics |
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| Online Access: | https://doi.org/10.1186/s40246-024-00601-z |
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| author | Xiayin Zhang Shan Wang Shunming Liu Zijing Du Guanrong Wu Yingying Liang Yu Huang Xianwen Shang Yijun Hu Zhuoting Zhu Wei Sun Xueli Zhang Honghua Yu |
| author_facet | Xiayin Zhang Shan Wang Shunming Liu Zijing Du Guanrong Wu Yingying Liang Yu Huang Xianwen Shang Yijun Hu Zhuoting Zhu Wei Sun Xueli Zhang Honghua Yu |
| author_sort | Xiayin Zhang |
| collection | DOAJ |
| description | Abstract Age-related cataract and hearing difficulties are major sensory disorders that often co-exist in the global-wide elderly and have a tangible influence on the quality of life. However, the epidemiologic association between cataract and hearing difficulties remains unexplored, while little is known about whether the two share their genetic etiology. We first investigated the clinical association between cataract and hearing difficulties using the UK Biobank covering 502,543 individuals. Both unmatched analysis (adjusted for confounders) and a matched analysis (one control matched for each patient with cataract according to confounding factors) were undertaken and confirmed that cataract was associated with hearing difficulties (OR, 2.12; 95% CI, 1.98–2.27; OR, 2.03; 95% CI, 1.86–2.23, respectively). Furthermore, we explored and quantified the shared genetic architecture of these two complex sensory disorders at the common variant level using the bivariate causal mixture model (MiXeR) and conditional/conjunctional false discovery rate method based on the largest available genome-wide association studies of cataract (N = 585,243) and hearing difficulties (N = 323,978). Despite detecting only a negligible genetic correlation, we observe polygenic overlap between cataract and hearing difficulties and identify 6 shared loci with mixed directions of effects. Follow-up analysis of the shared loci implicates candidate genes QKI, STK17A, TYR, NSF, and TCF4 likely contribute to the pathophysiology of cataracts and hearing difficulties. In conclusion, this study demonstrates the presence of epidemiologic association between cataract and hearing difficulties and provides new insights into the shared genetic architecture of these two disorders at the common variant level. |
| format | Article |
| id | doaj-art-3cf09ba2434542b38cd3d44133fbf497 |
| institution | DOAJ |
| issn | 1479-7364 |
| language | English |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Human Genomics |
| spelling | doaj-art-3cf09ba2434542b38cd3d44133fbf4972025-08-20T02:56:12ZengBMCHuman Genomics1479-73642024-04-0118111110.1186/s40246-024-00601-zEpidemiologic association and shared genetic architecture between cataract and hearing difficulties among middle-aged and older adultsXiayin Zhang0Shan Wang1Shunming Liu2Zijing Du3Guanrong Wu4Yingying Liang5Yu Huang6Xianwen Shang7Yijun Hu8Zhuoting Zhu9Wei Sun10Xueli Zhang11Honghua Yu12Department of Ophthalmology, Guangdong Eye Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical UniversityDepartment of Ophthalmology, Guangdong Eye Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical UniversityDepartment of Ophthalmology, Guangdong Eye Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical UniversityDepartment of Ophthalmology, Guangdong Eye Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical UniversityDepartment of Ophthalmology, Guangdong Eye Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical UniversityDepartment of Ophthalmology, Guangzhou First people’s HospitalDepartment of Ophthalmology, Guangdong Eye Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical UniversityDepartment of Ophthalmology, Guangdong Eye Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical UniversityDepartment of Ophthalmology, Guangdong Eye Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical UniversityCentre for Eye Research Australia, Royal Victorian Eye and Ear HospitalDepartment of Ophthalmology, Guangdong Eye Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical UniversityDepartment of Ophthalmology, Guangdong Eye Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical UniversityDepartment of Ophthalmology, Guangdong Eye Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical UniversityAbstract Age-related cataract and hearing difficulties are major sensory disorders that often co-exist in the global-wide elderly and have a tangible influence on the quality of life. However, the epidemiologic association between cataract and hearing difficulties remains unexplored, while little is known about whether the two share their genetic etiology. We first investigated the clinical association between cataract and hearing difficulties using the UK Biobank covering 502,543 individuals. Both unmatched analysis (adjusted for confounders) and a matched analysis (one control matched for each patient with cataract according to confounding factors) were undertaken and confirmed that cataract was associated with hearing difficulties (OR, 2.12; 95% CI, 1.98–2.27; OR, 2.03; 95% CI, 1.86–2.23, respectively). Furthermore, we explored and quantified the shared genetic architecture of these two complex sensory disorders at the common variant level using the bivariate causal mixture model (MiXeR) and conditional/conjunctional false discovery rate method based on the largest available genome-wide association studies of cataract (N = 585,243) and hearing difficulties (N = 323,978). Despite detecting only a negligible genetic correlation, we observe polygenic overlap between cataract and hearing difficulties and identify 6 shared loci with mixed directions of effects. Follow-up analysis of the shared loci implicates candidate genes QKI, STK17A, TYR, NSF, and TCF4 likely contribute to the pathophysiology of cataracts and hearing difficulties. In conclusion, this study demonstrates the presence of epidemiologic association between cataract and hearing difficulties and provides new insights into the shared genetic architecture of these two disorders at the common variant level.https://doi.org/10.1186/s40246-024-00601-zCataractHearing difficultiesShared genetic architectureSensory traitsOxidative stress |
| spellingShingle | Xiayin Zhang Shan Wang Shunming Liu Zijing Du Guanrong Wu Yingying Liang Yu Huang Xianwen Shang Yijun Hu Zhuoting Zhu Wei Sun Xueli Zhang Honghua Yu Epidemiologic association and shared genetic architecture between cataract and hearing difficulties among middle-aged and older adults Human Genomics Cataract Hearing difficulties Shared genetic architecture Sensory traits Oxidative stress |
| title | Epidemiologic association and shared genetic architecture between cataract and hearing difficulties among middle-aged and older adults |
| title_full | Epidemiologic association and shared genetic architecture between cataract and hearing difficulties among middle-aged and older adults |
| title_fullStr | Epidemiologic association and shared genetic architecture between cataract and hearing difficulties among middle-aged and older adults |
| title_full_unstemmed | Epidemiologic association and shared genetic architecture between cataract and hearing difficulties among middle-aged and older adults |
| title_short | Epidemiologic association and shared genetic architecture between cataract and hearing difficulties among middle-aged and older adults |
| title_sort | epidemiologic association and shared genetic architecture between cataract and hearing difficulties among middle aged and older adults |
| topic | Cataract Hearing difficulties Shared genetic architecture Sensory traits Oxidative stress |
| url | https://doi.org/10.1186/s40246-024-00601-z |
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