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Masahiro Miyake, Kenji Yamashiro, Hideo Nakanishi, Isao Nakata, Yumiko Akagi-Kurashige, Kyoko Kumagai, Akitaka Tsujikawa, Ryo Yamada, Fumihiko Matsuda, Nagahisa Yoshimura, Nagahama Study Group; Heritability Estimation of Axial Length and Refractive Error Explained by Genome-Wide Single Nucleotide Polymorphisms. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1734.
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Genome-wide association study (GWAS) is a powerful strategy which has identified numerous loci associated with diseases. However, although many GWASs have been conducted on high myopia, single nucleotide polymorphisms (SNPs) identified in them can explain only a small fraction of narrow-meaning heritability estimated by family studies or twin studies. Thus, we examined if SNPs typed in the GWAS can explain narrow-meaning heritability of AL and SE.
The Nagahama cohort study is an ongoing community-based cohort study, which consists of 9,804 individuals from Nagahama city, Japan. We used 3,748 individuals who are genotyped and imputed for 1,751,558 SNPs. After pruning potential relatives, 2171 individuals were finally included. Heritability is defined as a fraction of variance explained by all SNPs to that of the target phenotype, i.e. AL and SE. We estimated both variance explained by all SNPs and variance explained by SNPs in each chromosome by a linear mixed model proposed by Yang J. et al. (Nature Genetics, 2010). Age, sex, and height were included in the model as covariates.
For AL and SE, heritability (± standard error) explained by all SNPs were 40.0% (± 21.2) and 61.1% (± 24.8), respectively. While the top contributor for AL was chromosome 1 explaining 11.0%, no contribution was observed in chromosome 3, 7, and 11. Though five chromosomes contributed to heritability of SE explaining more than 5.0% respectively, ten chromosomes exhibited less than 0.5% of contribution.
Since the estimated heritability in this study is larger than the heritability explained by previously reported SNPs, GWAS still has a potential to identify more causative loci. The difference from the heritability estimated by family or twin study would be due to the rare variants or structural variations. SE is more common-SNP-driven than AL, and responsible chromosome of SE heritability is deviated.
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