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Yu Huang, Chea-Su Kee, Shea-Ping Yip, Jeremy A Guggenheim; A genome-wide association study (GWAS) for myopia susceptibility in chicks. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5634.
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Genome-wide association studies (GWAS) in human participants have successfully identified genetic variants associated with myopia susceptibility. However, GWAS approaches have had less success in identifying gene-environment (G×E) interactions. Aiming to reduce variability in environment exposures compared to children, we performed a GWAS for myopia susceptibility in the chick model.
White leghorn chicks 7 days old were monocularly form deprived for 4 days, in batches of approximately 20 individuals. The degree of induced myopia was quantified by A-scan ultrasonography and retinoscopy. From each batch, 20% of chicks with the highest or lowest treatment-induced axial length change (ΔAXL) were genotyped on a commercial Affymetrix SNP array. Using PLINK, ΔAXL elongation was analyzed as a continuous trait (dependent variable) with independent variables, SNP, sex, batch, and body weight.
In 986 chicks from 48 batches, ΔAXL averaged 0.55 ± 0.17 mm (mean ± S.D.). Chicks with a relatively low degree of induced myopia (n=190; ΔAXL=0.31 ± 0.08 mm) and a relatively high degree of induced myopia (n=190; ΔAXL=0.78 ± 0.08 mm) were genotyped (average call rate 99.5%). SNPs with call rate <95% or minor allele frequency <0.1, and samples with heterozygosity >0.4 were excluded, leaving 379 samples and 354,147 SNPs. After genomic control correction for relatedness (lambda = 1.22), regions on chromosomes 1 and 7 exceeded the suggestive association threshold (P <1e-05). The nearest genes were a cAMP-dependent protein kinase subunit and a member of the UDP glucuronosyltransferase family, respectively. The former gene has previously been implicated in myopia development in the chick model. These association peaks are being followed-up using RNA-seq analysis.
This study is the first report of a GWAS for myopia susceptibility in an animal model of myopia. The human homologues of the genes located on chick chromosomes 1 and 7 are being investigated for potential involvement in human myopia via G×E interactions.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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