Genetic variants on chromosome 1q41 influence ocular axial length and high myopia.
As one of the leading causes of visual impairment and blindness, myopia poses a significant public health burden in Asia. The primary determinant of myopia is an elongated ocular axial length (AL). Here we report a meta-analysis of three genome-wide association studies on AL conducted in 1,860 Chinese adults, 929 Chinese children, and 2,155 Malay adults. We identified a genetic locus on chromosome 1q41 harboring the zinc-finger 11B pseudogene ZC3H11B showing genome-wide significant association with AL variation (rs4373767, β = -0.16 mm per minor allele, P(meta) =2.69 × 10(-10)). The minor C allele of rs4373767 was also observed to significantly associate with decreased susceptibility to high myopia (per-allele odds ratio (OR) =0.75, 95% CI: 0.68-0.84, P(meta) =4.38 × 10(-7)) in 1,118 highly myopic cases and 5,433 controls. ZC3H11B and two neighboring genes SLC30A10 and LYPLAL1 were expressed in the human neural retina, retinal pigment epithelium, and sclera. In an experimental myopia mouse model, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for the murine genes ZC3H11A, SLC30A10, and LYPLAL1. This supports the likely role of genetic variants at chromosome 1q41 in influencing AL variation and high myopia.
Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
Qiao
Q
Fan
Veluchamy A
VA
Barathi
Ching-Yu
CY
Cheng
Xin
X
Zhou
Akira
A
Meguro
Isao
I
Nakata
Chiea-Chuen
CC
Khor
Liang-Kee
LK
Goh
Yi-Ju
YJ
Li
Wan'e
W
Lim
Candice E H
CE
Ho
Felicia
F
Hawthorne
Yingfeng
Y
Zheng
Daniel
D
Chua
Hidetoshi
H
Inoko
Kenji
K
Yamashiro
Kyoko
K
Ohno-Matsui
Keitaro
K
Matsuo
Fumihiko
F
Matsuda
Eranga
E
Vithana
Mark
M
Seielstad
Nobuhisa
N
Mizuki
Roger W
RW
Beuerman
E-Shyong
ES
Tai
Nagahisa
N
Yoshimura
Tin
T
Aung
Terri L
TL
Young
Tien-Yin
TY
Wong
Yik-Ying
YY
Teo
Seang-Mei
SM
Saw
D000328:Adult; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics; D002648:Child; D002681:China; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008245:Lysophospholipase / Q000235:genetics; D008297:Male; D051379:Mice; D008875:Middle Aged; D009216:Myopia / Q000235:genetics*; D009687:Nuclear Proteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016601:RNA-Binding Proteins; D012160:Retina / Q000378:metabolism / Q000473:pathology; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D012590:Sclera / Q000378:metabolism / Q000473:pathology; D000075703:Zinc Transporter 8
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C492522:SLC30A8 protein, human; C547914:Zc3h11a protein, mouse; D000075703:Zinc Transporter 8; D008245:Lysophospholipase; C561408:LYPLAL1 protein, human