title: Genetic variants at 13q12.12 are associated with high myopia in the Han Chinese population.
abstract: High myopia, which is extremely prevalent in the Chinese population, is one of the leading causes of blindness in the world. Genetic factors play a critical role in the development of the condition. To identify the genetic variants associated with high myopia in the Han Chinese, we conducted a genome-wide association study (GWAS) of 493,947 SNPs in 1088 individuals (419 cases and 669 controls) from a Han Chinese cohort and followed up on signals that were associated with p < 1.0 × 10(-4) in three independent cohorts (combined, 2803 cases and 5642 controls). We identified a significant association between high myopia and a variant at 13q12.12 (rs9318086, combined p = 1.91 × 10(-16), heterozygous odds ratio = 1.32, and homozygous odds ratio = 1.64). Furthermore, five additional SNPs (rs9510902, rs3794338, rs1886970, rs7325450, and rs7331047) in the same linkage disequilibrium (LD) block with rs9318086 also proved to be significantly associated with high myopia in the Han Chinese population; p values ranged from 5.46 × 10(-11) to 6.16 × 10(-16). This associated locus contains three genes-MIPEP, C1QTNF9B-AS1, and C1QTNF9B. MIPEP and C1QTNF9B were found to be expressed in the retina and retinal pigment epithelium (RPE) and are more likely than C1QTNF9B-AS1 to be associated with high myopia given the evidence of retinal signaling that controls eye growth. Our results suggest that the variants at 13q12.12 are associated with high myopia.
authors.affiliation: The Sichuan Provincial Key Laboratory for Human Disease Gene Study and The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.affiliation: School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang 325035, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
authors.affiliation: The Sichuan Provincial Key Laboratory for Human Disease Gene Study and The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Dingding
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Xinhua Hospital, Shanghai Jiaotong University, Shanghai 200092, China.
authors.forename: Peiquan
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authors.lastname: Zhao
authors.affiliation: Zhongshan Ophthalmic Center, Guangzhou, Guangdong 510060, China.
authors.forename: Qingjiong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong, China.
authors.forename: Pancy Oi Sin
authors.initials: POS
authors.lastname: Tam
authors.affiliation: China Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui 230032, China.
authors.forename: Liangdan
authors.initials: L
authors.lastname: Sun
authors.affiliation: China Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui 230032, China.
authors.forename: Xianbo
authors.initials: X
authors.lastname: Zuo
authors.affiliation: School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang 325035, China.
authors.forename: Xiangtian
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authors.lastname: Zhou
authors.affiliation: Zhongshan Ophthalmic Center, Guangzhou, Guangdong 510060, China.
authors.forename: Xueshan
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Ophthalmology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Hu
authors.affiliation: The Sichuan Provincial Key Laboratory for Human Disease Gene Study and The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Yuanfeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Sichuan Provincial Key Laboratory for Human Disease Gene Study and The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Li
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authors.lastname: Cai
authors.affiliation: The Sichuan Provincial Key Laboratory for Human Disease Gene Study and The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Liu
authors.affiliation: The Sichuan Provincial Key Laboratory for Human Disease Gene Study and The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Lu
authors.affiliation: Department of Ophthalmology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Shihuang
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authors.lastname: Liao
authors.affiliation: Department of Ophthalmology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.affiliation: The Sichuan Provincial Key Laboratory for Human Disease Gene Study and The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Fei
authors.initials: F
authors.lastname: He
authors.affiliation: The Sichuan Provincial Key Laboratory for Human Disease Gene Study and The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Bo
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authors.lastname: Gong
authors.affiliation: The Sichuan Provincial Key Laboratory for Human Disease Gene Study and The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: He
authors.initials: H
authors.lastname: Lin
authors.affiliation: The Sichuan Provincial Key Laboratory for Human Disease Gene Study and The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Shi
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authors.affiliation: The Sichuan Provincial Key Laboratory for Human Disease Gene Study and The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Jing
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authors.affiliation: Shiji Eye Hospital, Chengdu, Sichuan 610016, China.
authors.forename: Jie
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authors.affiliation: Department of Ophthalmology, Xinhua Hospital, Shanghai Jiaotong University, Shanghai 200092, China.
authors.forename: Yiye
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authors.affiliation: School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang 325035, China.
authors.forename: Fuxin
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authors.affiliation: The Department of Ophthalmology, Medical College of Qingdao University, The Affiliated Hospital of Medical College Qingdao University, Qingdao 266003, China.
authors.forename: Xian
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authors.affiliation: Department of Ophthalmology and Visual Science, Eye and ENT Hospital, Shanghai Medical School, Fudan University, Shanghai 200031, China.
authors.forename: Yuhong
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authors.affiliation: West High School, Salt Lake City, Utah 84103, USA.
authors.forename: Charles
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authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong, China.
authors.forename: Dennis Shun Chiu
authors.initials: DSC
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authors.affiliation: The Sichuan Provincial Key Laboratory for Human Disease Gene Study and The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Xi
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authors.affiliation: School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang 325035, China.
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authors.affiliation: Department of Ophthalmology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Zhengzheng
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authors.affiliation: The Sichuan Provincial Key Laboratory for Human Disease Gene Study and The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Ying
authors.initials: Y
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authors.affiliation: The Sichuan Provincial Key Laboratory for Human Disease Gene Study and The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
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authors.affiliation: Zhongshan Ophthalmic Center, Guangzhou, Guangdong 510060, China.
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authors.affiliation: Department of Ophthalmology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Yingchuan
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authors.affiliation: Molecular Medicine, University of Utah, Salt Lake City, Utah 84132, USA.
authors.forename: Dean
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authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong, China.
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authors.affiliation: The Sichuan Provincial Key Laboratory for Human Disease Gene Study and The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China. Electronic address: zliny@yahoo.com.
authors.forename: Zhenglin
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mesh_terms: D052242:Adiponectin / Q000235:genetics; D044466:Asian People / Q000235:genetics; D002681:China / Q000208:ethnology; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics; D009216:Myopia / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012160:Retina / Q000378:metabolism; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
chemical_list: D052242:Adiponectin; C543615:C1QTNF9B protein, human; D006023:Glycoproteins; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D008666:Metalloendopeptidases; C068038:mitochondrial intermediate peptidase