A genome-wide association analysis identified a novel susceptible locus for pathological myopia at 11q24.1.
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 = 2.22x10(-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.
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Hideo
H
Nakanishi
Ryo
R
Yamada
Norimoto
N
Gotoh
Hisako
H
Hayashi
Kenji
K
Yamashiro
Noriaki
N
Shimada
Kyoko
K
Ohno-Matsui
Manabu
M
Mochizuki
Masaaki
M
Saito
Tomohiro
T
Iida
Keitaro
K
Matsuo
Kazuo
K
Tajima
Nagahisa
N
Yoshimura
Fumihiko
F
Matsuda
D044466:Asian People / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study; D006367:HeLa Cells; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D047728:Myopia, Degenerative / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012160:Retina / Q000378:metabolism / Q000473:pathology
D005819:Genetic Markers