Heritability of Central Corneal Thickness in Chinese: The Guangzhou Twin Eye Study

Zheng, Yingfeng; Ge, Junbo; Huang, Guofu; Zhang, Jian; Liu, Bin; Hur, Yoon‐Mi; He, Mingguang

doi:10.1167/iovs.08-1934

Cited by 69 publications

(58 citation statements)

References 32 publications

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“…Within the general population, CCT is a normally distributed quantitative trait, with evidence from twin studies suggesting that it is highly heritable (Toh et al 2005;Zheng et al 2008). However, despite its high heritability, no genes have been identiWed to date that contribute to CCT variation in the normal population.…”

Section: Introductionmentioning

confidence: 99%

Novel quantitative trait loci for central corneal thickness identified by candidate gene analysis of osteogenesis imperfecta genes

et al. 2009

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Osteogenesis imperfecta (OI) is a rare connective tissue disorder caused by mutations in the type I collagen genes, COL1A1 and COL1A2, and is characterised by low bone mass and bone fragility. In this study, we explored the relationship between type 1 collagen genes and the quantitative trait central corneal thickness (CCT). CCT was measured in a cohort of 28 Australian type I OI patients and mean CCT was found to be significantly lower compared to a normal population (P < 0.001). We then investigated CCT and corneal collagen fibril diameter and density in a mouse model of OI with a col1a2 mutation. Mean CCT was significantly lower in mutant mice (P = 0.002), as was corneal collagen fibril diameter (P = 0.034), whilst collagen fibril density was significantly greater in mutants (P = 0.034). Finally, we conducted a genetic study to determine whether common single nucleotide polymorphisms (SNPs) in COL1A1 and COL1A2 are associated with CCT variation in the normal human population. Polymorphism rs2696297 (P = 0.003) in COL1A1 and a three SNP haplotype in COL1A2 (P = 0.007) were all significantly associated with normal CCT variation. These data implicate type 1 collagen in the determination of CCT in both OI patients and normal individuals. This provides the first evidence of quantitative trait loci that influence CCT in a normal population and has potential implications for investigating genes involved in glaucoma pathogenesis, a common eye disease in which the severity and progression is influenced by CCT.

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Section: Introductionmentioning

confidence: 99%

Novel quantitative trait loci for central corneal thickness identified by candidate gene analysis of osteogenesis imperfecta genes

et al. 2009

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“…2,3,14,[20][21][22] Despite this high heritability and the fact that CCT has been implicated in several human diseases, currently known genetic variations explain only a small fraction of this phenotypic variability. Of the genes known to influence the normal range of CCT variation, most were identified in human genome-wide association studies (GWAS).…”

Section: -19mentioning

confidence: 99%

Genetic Evidence for Differential Regulation of Corneal Epithelial and Stromal Thickness

Koehn

Meyer

Anderson

2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Central corneal thickness (CCT) is a quantitative trait associated with keratoconusand primary open-angle glaucoma. Although CCT is highly heritable, known genetic variations explain only a fraction of the phenotypic variability. The purpose of this study was to identify additional CCT-influencing loci using inbred strains of mice.METHODS. Cohorts of 82 backcrossed (N2) and 99 intercrossed (F2) mice were generated from crosses between recombinant inbred BXD24/TyJ and wild-derived CAST/EiJ mice. Using anterior chamber optical coherence tomography, mice were phenotyped at 10 to 12 weeks of age, genotyped based on 96 genome-wide single nucleotide polymorphisms (SNPs), and subjected to quantitative trait locus (QTL) analysis. RESULTS.In an analysis of total CCT among all mice, two loci passed the significance threshold of P ¼ 0.05. These were on Chr 3 and Chr 11 (Cctq4 and Cctq5, respectively). A third locus of interest was identified in a two-dimensional pairwise analysis; this locus on Chr 14 (Cctq6) exhibited a significant additive effect with Cctq5. Independent analyses of the dataset for epithelial and stromal thickness revealed that Cctq4 is specific to the epithelial layer and that Cctq5 and Cctq6 are specific to the stromal layer.CONCLUSIONS. Our findings demonstrate a quantitative multigenic pattern of CCT inheritance in mice and identify three previously unrecognized CCT-influencing loci: Cctq4, Cctq5, and Cctq6. This is the first demonstration that distinct layers of the cornea are under differential genetic control and highlights the need to refine the design of future genome-wide association studies of CCT.Keywords: quantitative traits, central corneal thickness, cornea, QTL analysis C entral corneal thickness (CCT) is a continuously distributed quantitative trait.1-4 As a sum of the thickness of the three corneal tissue layers (the epithelium, stroma, and endothelium), CCT remains relatively stable over time within individuals, but varies widely between individuals and ethnicities. [5][6][7][8][9][10] Extreme variations in CCT are often associated with rare connective tissue disorders such as brittle cornea syndrome and osteogenesis imperfecta, 11-15 whereas modest differences are associated with relatively common diseases such as keratoconus 16 and risk of primary open-angle glaucoma. 17-19Central corneal thickness is one of the most heritable human traits, with estimates of up to 0.95 reported. 2,3,14,[20][21][22] Despite this high heritability and the fact that CCT has been implicated in several human diseases, currently known genetic variations explain only a small fraction of this phenotypic variability. Of the genes known to influence the normal range of CCT variation, most were identified in human genome-wide association studies (GWAS). 13,16,[23][24][25] Several of the currently known CCT-influencing factors include genes that have an impact on collagen, 16,24,25 a major structural component of the stromal layer. Other CCT-influencing genes have unknown function, including ZNF469, a zi...

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“…[34][35][36][37] On the other hand, some studies did not find that central corneal thickness increases with age for children >8 years of age. 38 Most of the studies evaluating the relationship of birth weight with corneal thickness were usually performed in premature infants or on infants in the early weeks of life and no relationship was found between birth weight and central corneal thickness. 8-10, 13, 36, 39 Similarly, Rushood et al recently measured central corneal thickness in 100 (n=200 eyes) normal, full-term Saudi newborns during the first 6 days of life.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Effects of Birth Weight on Anterior Segment Measurements in Full-Term Children Without Low Birth Weight by Dual-Scheimpflug Analyzer

Yeter

Arıtürk

Birinci

et al. 2015

American Journal of Ophthalmology

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Heritability of Central Corneal Thickness in Chinese: The Guangzhou Twin Eye Study

Abstract: Additive genetic effects appear to be the major contributor to the variation of CCT in Chinese population. Heritability of CCT appears to be slightly greater in the girls than in the boys.

Cited by 69 publications

References 32 publications

Novel quantitative trait loci for central corneal thickness identified by candidate gene analysis of osteogenesis imperfecta genes

Novel quantitative trait loci for central corneal thickness identified by candidate gene analysis of osteogenesis imperfecta genes

Genetic Evidence for Differential Regulation of Corneal Epithelial and Stromal Thickness

Effects of Birth Weight on Anterior Segment Measurements in Full-Term Children Without Low Birth Weight by Dual-Scheimpflug Analyzer

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