Elsevier

Ophthalmology

Volume 120, Issue 2, February 2013, Pages 292-297
Ophthalmology

Original article
Genetic Association of Refractive Error and Axial Length with 15q14 but Not 15q25 in the Blue Mountains Eye Study Cohort

https://doi.org/10.1016/j.ophtha.2012.08.006Get rights and content

Purpose

Myopia is a common complex condition influenced by genetic and environmental factors. Two recent genome-wide association studies have identified loci on chromosomes 15q25 and 15q14 associated with refractive error in Caucasian populations. Our study aimed to assess the association of these 2 loci with refractive error and ocular biometric measures in an independent ethnically matched Caucasian cohort.

Design

Genetic association study using unrelated individuals.

Participants

Blue Mountains Eye Study (BMES) cohort. A total of 1571 individuals were included in this study.

Methods

Single nucleotide polymorphism (SNP) genotype data were collected from the BMES cohort as part of the Wellcome Trust Case Control Consortium 2. Imputation was performed using MACH version 1.1.16, and statistical analysis was conducted using PLINK. Association tests were performed at both loci using refractive error (spherical equivalent), axial length, corneal curvature, and anterior chamber depth as the phenotypes.

Main Outcome Measures

Refractive error, axial length, corneal curvature, and anterior chamber depth.

Results

A total of 1571 individuals were available from the BMES for analysis. A statistically significant association for refractive error was evident for SNPs at the 15q14 locus, with P values ranging from 1.5×10−2 at rs685352 to 6.4×10−4 at rs560764, whereas association could not be confirmed for SNPs at the 15q25 locus, with P values ranging from 8.0×10−1 to 6.4×10−1. Ocular biometric analysis revealed that axial length was the most likely trait underlying the refractive error association at the 15q14 locus for SNPs rs560766 (P=0.0054), rs634990 (P=0.0086), and rs8032019 (P=0.0081).

Conclusions

Our results confirm the association with refractive error at the 15q14 locus but do not support the association observed at the 15q25 locus. Axial length seemed to be a major parameter at the 15q14 locus, underscoring the importance of this locus in myopia and future clinical treatment.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Section snippets

Ethics Statement

This study was conducted after approval from the Human Ethics Research Committee at the University of Sydney and the Western Sydney Area Health Service. All participants provided written, informed consent in accordance with the Declaration of Helsinki.

Participants and Examination

The BMES is a population-based longitudinal survey of vision and common eye diseases that has followed residents in an area west of Sydney, New South Wales, Australia, over a 15-year time period. This suburban area has a stable and homogeneous

Clinical Information

All tested SNPs at the 15q14 and 15q25 loci remained in the analysis after application of the SNP filtering criteria. A total of 1571 individuals remained in our final analysis after application of the sample filtering criteria. In the trimmed cohort, 43.0% were female and 57.0% were male. The average age of participants was 73.84±7.81 years, and the average spherical equivalent measure was +0.59±2.17 D (range, −13.56 to +8.56 D). The average axial length was 23.44±1.0 mm (range, 28.45–19.94

Discussion

The data presented confirm an association of refractive error with the 15q14 locus initially reported by both Solouki et al,10 with SNPs rs524952 and rs634990 showing the strongest association. In the case of the 15q25 locus reported by Hysi et al,9 we were not able to demonstrate association for any SNPs at this locus using the BMES cohort. In addition, we were able to show that the ocular biometric trait of axial length seems to be a contributor to the effect seen at the 15q14 locus, implying

References (16)

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Cited by (0)

Manuscript no. 2012-314.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Funding: National Health and Medical Research Council, Canberra, Australia (Project Grants: 974159, 211069, 457349, 512423, 475604, and 529912); Centre for Clinical Research Excellence in Translational Clinical Research in Eye Diseases; National Health & Medical Research Council research fellowships to P.N.B. (No. 1028444 and J.J.W. (No. 358702, 632909); Wellcome Trust as part of the Wellcome Trust Case Control Consortium 2 (No. 085475B08Z, 08547508Z, 076113); Medical Research Council (UK) (G0401527); Fight for Sight (London); and National Institute for Health Research grant for a Biomedical Research Centre for Ophthalmology. This study used genotyping data generated and funded by the Wellcome Trust Case-Control Consortium 2 using samples from the BMES.

A full list of contributing investigators to the generation of these data is available online in Appendix 1 (http://aaojournal.org).

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Group members listed online in Appendix 1 (http://aaojournal.org).

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