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Hum Mol Genet. 2014 Nov 15;23(22):6129-36. doi: 10.1093/hmg/ddu322. Epub 2014 Jun 24.

CMPK1 and RBP3 are associated with corneal curvature in Asian populations.

Author information

1
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore.
2
Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan.
3
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore, Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore.
4
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore, Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore, Memory Aging & Cognition Centre, National University Health System, Singapore 117597, Singapore.
5
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore.
6
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore, Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore, Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
7
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore, Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore, Department of Paediatrics.
8
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore, Duke-NUS Graduate Medical School, Singapore 169857, Singapore, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
9
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore, NUS Graduate School for Integrative Science and Engineering, Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore and Department of Statistics and Applied Probability, National University of Singapore, Singapore 117546, Singapore.
10
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore, Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore.
11
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597, Singapore, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore, Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore, Duke-NUS Graduate Medical School, Singapore 169857, Singapore, ching-yu_cheng@nuhs.edu.sg.

Abstract

Corneal curvature (CC) measures the steepness of the cornea and is an important parameter for clinically diseases such as astigmatism and myopia. Despite the high heritability of CC, only two associated genes have been discovered to date. We performed a three-stage genome-wide association study meta-analysis in 12 660 Asian individuals. Our Stage 1 was done in multiethnic cohorts comprising 7440 individuals, followed by a Stage 2 replication in 2473 Chinese and Stage 3 in 2747 Japanese. The SNP array genotype data were imputed up to the 1000 Genomes Project Phase 1 cosmopolitan panel. The SNP association with the radii of CC was investigated in the linear regression model with the adjustment of age, gender and principal components. In addition to the known genes, MTOR (also known as FRAP1) and PDGFRA, we discovered two novel genes associated with CC: CMPK1 (rs17103186, P = 3.3 × 10(-12)) and RBP3 (rs11204213 [Val884Met], P = 1.1 × 10(-13)). The missense RBP3 SNP, rs11204213, was also associated with axial length (AL) (P = 4.2 × 10(-6)) and had larger effects on both CC and AL compared with other SNPs. The index SNPs at the four indicated loci explained 1.9% of CC variance across the Stages 1 and 2 cohorts, while 33.8% of CC variance was explained by the genome-wide imputation data. We identified two novel genes influencing CC, which are related to either corneal shape or eye size. This study provides additional insights into genetic architecture of corneal shape.

PMID:
24963161
DOI:
10.1093/hmg/ddu322
[Indexed for MEDLINE]
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