Myopia 20, Autosomal Dominant

Description

Myopia, or nearsightedness, is a refractive error of the eye. Light rays from a distant object are focused in front of the retina and those from a near object are focused in the retina; therefore distant objects are blurry and near objects are clear (summary by Kaiser et al., 2004).

For a discussion of genetic heterogeneity of susceptibility to myopia, see 160700.

Mapping

Shi et al. (2011) conducted a genomewide association study of 493,947 SNPs in 419 Han Chinese individuals with high myopia and 669 unrelated controls and found that none of the SNPs were significantly associated after correction for multiple testing; however, 34 SNPs in 22 chromosomal regions were associated after adjustment for genomic control, gender, and age, with nominal p values less than 10(-4). Testing those 34 SNPs in a follow-up cohort of 843 Han Chinese individuals with high myopia and 2,525 controls yielded a significant association between SNP rs9318086 at chromosome 13q12.12 and high myopia after adjustment for gender and age (heterozygous odds ratio (OR), 1.40; homozygous OR, 1.68; corrected p = 7.75 x 10 (-5)). Analysis of 9 SNPs within 200 kb of rs9318086 revealed 5 SNPs with a p value of less than 3.6 x 10(-4), all of which are within a linkage disequilibrium (LD) block spanning 47 kb from rs9507174 to rs9551019. One of the SNPs, rs1886970, is located in intron 14 of the MIPEP gene (602241) and is in complete LD with rs9318086, located in intron 10 of MIPEP. Shi et al. (2011) genotyped rs1886970 in the follow-up cohort and found significant association with high myopia after correction for gender and age (heterozygous OR, 1.35; homozygous OR, 1.63; p = 1.33 x 10(-5)). Shi et al. (2011) concluded that this locus was likely to be associated with high myopia, and confirmed the finding by genotyping rs9318086 and rs1886970 in 2 additional follow-up datasets, obtaining a combined allelic p value for rs9318086 for all 4 cohorts of 1.91 x 10(-16) after adjustment for gender and age (heterozygous OR, 1.32; homozygous OR, 1.64). The direction of the effect was consistent in all cohorts studied. Shi et al. (2011) noted that of 3 genes contained in the locus, 2 are expressed in the retina and retinal pigment epithelium: MIPEP and C1QTNF9B (614148).