Mendelian Randomisation Analysis of Causal Association between Lifestyle, Health Factors, and Keratoconus
Keratoconus (KC), a leading cause of vision impairment, has an unclear aetiology. This study used Mendelian randomization (MR) to explore the causal links between various factors (smoking, asthma, Down syndrome, inflammatory bowel disease, atopic dermatitis, and serum 25-hydroxyvitamin D levels) and...
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MDPI AG
2024-02-01
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| Series: | Bioengineering |
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| Online Access: | https://www.mdpi.com/2306-5354/11/3/221 |
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| author | Jiaxuan Cheng Lanting Yang Yishan Ye Lvfu He Shihao Chen Junjie Wang |
| author_facet | Jiaxuan Cheng Lanting Yang Yishan Ye Lvfu He Shihao Chen Junjie Wang |
| author_sort | Jiaxuan Cheng |
| collection | DOAJ |
| description | Keratoconus (KC), a leading cause of vision impairment, has an unclear aetiology. This study used Mendelian randomization (MR) to explore the causal links between various factors (smoking, asthma, Down syndrome, inflammatory bowel disease, atopic dermatitis, and serum 25-hydroxyvitamin D levels) and KC. A two-sample MR design, grounded in genome-wide association study (GWAS) summary statistics, was adopted using data from FinnGen, UK Biobank, and other GWAS-related articles. The inverse-variance weighted (IVW) method was employed, complemented by the Wald ratio method for factors with only one single-nucleotide polymorphism (SNP). Sensitivity and stability were assessed through Cochrane’s Q test, the MR-Egger intercept test, MR-PRESSO outlier test, and the leave-one-out analysis. The IVW results for the ORA (Ocular Response Analyzer) biomechanical parameters indicated significant associations between tobacco smoking (CH: <i>p</i> < 0.001; CRF: <i>p</i> = 0.009) and inflammatory bowel disease (CH: <i>p</i> = 0.032; CRF: <i>p</i> = 0.001) and corneal biomechanics. The Wald ratio method showed tobacco smoking was associated with a lower risk of KC (<i>p</i> = 0.024). Conversely, asthma (<i>p</i> = 0.009), atopic dermatitis (<i>p</i> = 0.012), inflammatory bowel disease (<i>p</i> = 0.017), and serum 25-hydroxyvitamin D levels (<i>p</i> = 0.039) were associated with a higher risk of KC by IVW, and the same applied to Down syndrome (<i>p</i> = 0.004) using the Wald ratio. These results underscore the role of corneal biomechanics as potential mediators in KC risk, warranting further investigation using Corvis ST and Brillouin microscopy. The findings emphasise the importance of timely screening for specific populations in KC prevention and management. |
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| spelling | doaj.art-5040b411af184eb6a6f088f639f6b5242024-03-27T13:21:48ZengMDPI AGBioengineering2306-53542024-02-0111322110.3390/bioengineering11030221Mendelian Randomisation Analysis of Causal Association between Lifestyle, Health Factors, and KeratoconusJiaxuan Cheng0Lanting Yang1Yishan Ye2Lvfu He3Shihao Chen4Junjie Wang5National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaNational Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaNational Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaDepartment of Ophthalmology, Sichuan Mental Health Center, Mianyang 621054, ChinaNational Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaNational Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaKeratoconus (KC), a leading cause of vision impairment, has an unclear aetiology. This study used Mendelian randomization (MR) to explore the causal links between various factors (smoking, asthma, Down syndrome, inflammatory bowel disease, atopic dermatitis, and serum 25-hydroxyvitamin D levels) and KC. A two-sample MR design, grounded in genome-wide association study (GWAS) summary statistics, was adopted using data from FinnGen, UK Biobank, and other GWAS-related articles. The inverse-variance weighted (IVW) method was employed, complemented by the Wald ratio method for factors with only one single-nucleotide polymorphism (SNP). Sensitivity and stability were assessed through Cochrane’s Q test, the MR-Egger intercept test, MR-PRESSO outlier test, and the leave-one-out analysis. The IVW results for the ORA (Ocular Response Analyzer) biomechanical parameters indicated significant associations between tobacco smoking (CH: <i>p</i> < 0.001; CRF: <i>p</i> = 0.009) and inflammatory bowel disease (CH: <i>p</i> = 0.032; CRF: <i>p</i> = 0.001) and corneal biomechanics. The Wald ratio method showed tobacco smoking was associated with a lower risk of KC (<i>p</i> = 0.024). Conversely, asthma (<i>p</i> = 0.009), atopic dermatitis (<i>p</i> = 0.012), inflammatory bowel disease (<i>p</i> = 0.017), and serum 25-hydroxyvitamin D levels (<i>p</i> = 0.039) were associated with a higher risk of KC by IVW, and the same applied to Down syndrome (<i>p</i> = 0.004) using the Wald ratio. These results underscore the role of corneal biomechanics as potential mediators in KC risk, warranting further investigation using Corvis ST and Brillouin microscopy. The findings emphasise the importance of timely screening for specific populations in KC prevention and management.https://www.mdpi.com/2306-5354/11/3/221keratoconusMendelian randomisationcausal relationshipcorneal biomechanicsOcular Response Analyzer |
| spellingShingle | Jiaxuan Cheng Lanting Yang Yishan Ye Lvfu He Shihao Chen Junjie Wang Mendelian Randomisation Analysis of Causal Association between Lifestyle, Health Factors, and Keratoconus Bioengineering keratoconus Mendelian randomisation causal relationship corneal biomechanics Ocular Response Analyzer |
| title | Mendelian Randomisation Analysis of Causal Association between Lifestyle, Health Factors, and Keratoconus |
| title_full | Mendelian Randomisation Analysis of Causal Association between Lifestyle, Health Factors, and Keratoconus |
| title_fullStr | Mendelian Randomisation Analysis of Causal Association between Lifestyle, Health Factors, and Keratoconus |
| title_full_unstemmed | Mendelian Randomisation Analysis of Causal Association between Lifestyle, Health Factors, and Keratoconus |
| title_short | Mendelian Randomisation Analysis of Causal Association between Lifestyle, Health Factors, and Keratoconus |
| title_sort | mendelian randomisation analysis of causal association between lifestyle health factors and keratoconus |
| topic | keratoconus Mendelian randomisation causal relationship corneal biomechanics Ocular Response Analyzer |
| url | https://www.mdpi.com/2306-5354/11/3/221 |
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