Genetic association of refractive error and axial length with 15q14 but not 15q25 in the Blue Mountains Eye Study cohort

Abstract

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.