A Genome-Wide Association Analysis Identified a Novel Susceptible Locus for Pathological Myopia at 11q24.1

Abstract

Myopia is one of the most common ocular disorders worldwide. Pathological myopia, also called high myopia, comprises 1% to 5% of the general population and is one of the leading causes of legal blindness in developed countries. To identify genetic determinants associated with pathological myopia in Japanese, we conducted a genome-wide association study, analyzing 411,777 SNPs with 830 cases and 1,911 general population controls in a two-stage design (297 cases and 934 controls in the first stage and 533 cases and 977 controls in the second stage). We selected 22 SNPs that showed P-values smaller than 10−4 in the first stage and tested them for association in the second stage. The meta-analysis combining the first and second stages identified an SNP, rs577948, at chromosome 11q24.1, which was associated with the disease (P = 2.22×10−7 and OR of 1.37 with 95% confidence interval: 1.21–1.54). Two genes, BLID and LOC399959, were identified within a 200-kb DNA encompassing rs577948. RT–PCR analysis demonstrated that both genes were expressed in human retinal tissue. Our results strongly suggest that the region at 11q24.1 is a novel susceptibility locus for pathological myopia in Japanese.

A Genome-Wide Association Study Provides Evidence for Association of Chromosome 8p23 (MYP10) and 10q21.1 (MYP15) with High Myopia in the French Population

“…The first GWAS on high myopia was reported using Japanese cohorts and a region on 11q24.1 was identified. 8 Li et al 9 then located a high myopia locus on 5p15 using Japanese and Singaporean Chinese samples. Furthermore, genetic variants at 4q25 and 13q12.12 were revealed to be associated with high myopia in Han Chinese population.…”

Reply to Guggenheim et al

“…We must admit that we made errors in the statement of Hardy-Weinberg equilibrium (HWE). The text in one of our reports reads: 5 'In the test of HWE, there were departures from HWE for S1 in both the control and high myopia groups (P ¼ 0.048 and 0.023, respectively) and for S2 in the control group (P ¼ 0.012).' These values were not P values but were the results of HWEw 2 .…”

“…The S3 and S4 polymorphisms were not in HWE. ' We had explained the possible problems about departures from HWE in the fourth paragraph in the text, 5 and hoped this could decrease the doubt on genotyping or population stratification. Definitely, we must make painstaking efforts in our future studies.…”

Genome-wide association studies: applications and insights gained in Ophthalmology

“…81,82 Andrew et al 82 demonstrated an association of refractive error with MFN1, PSARL, and SOX2OT, while Nakanishi et al 81 identified a polymorphism (rs577948) at 11q24.1 (near BLID) that was associated with an elevated risk of pathological myopia (OR ¼ 1.37). MFN1, PSARL, and BLID are expressed in mitochondria and are involved in mitochondrial-led cellular apoptosis.…”

“…MFN1, PSARL, and BLID are expressed in mitochondria and are involved in mitochondrial-led cellular apoptosis. 83 In addition, a further GWAS identified a polymorphism (rs9318086) at 13q12.12 significantly associated with an increased risk of high myopia in a Han Chinese population (OR ¼ 1.64). 84 This region contains the genes MIPEP and C1QTNF9B-AS1.…”