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Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.

ABSTRACT: Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways.

SUBMITTER: Cheng CY

PROVIDER: S-EPMC3772747 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.

Cheng Ching-Yu CY Schache Maria M Ikram M Kamran MK Young Terri L TL Guggenheim Jeremy A JA Vitart Veronique V MacGregor Stuart S Verhoeven Virginie J M VJ Barathi Veluchamy A VA Liao Jiemin J Hysi Pirro G PG Bailey-Wilson Joan E JE St Pourcain Beate B Kemp John P JP McMahon George G Timpson Nicholas J NJ Evans David M DM Montgomery Grant W GW Mishra Aniket A Wang Ya Xing YX Wang Jie Jin JJ Rochtchina Elena E Polasek Ozren O Wright Alan F AF Amin Najaf N van Leeuwen Elisabeth M EM Wilson James F JF Pennell Craig E CE van Duijn Cornelia M CM de Jong Paulus T V M PT Vingerling Johannes R JR Zhou Xin X Chen Peng P Li Ruoying R Tay Wan-Ting WT Zheng Yingfeng Y Chew Merwyn M Burdon Kathryn P KP Craig Jamie E JE Iyengar Sudha K SK Igo Robert P RP Lass Jonathan H JH Chew Emily Y EY Haller Toomas T Mihailov Evelin E Metspalu Andres A Wedenoja Juho J Simpson Claire L CL Wojciechowski Robert R Höhn René R Mirshahi Alireza A Zeller Tanja T Pfeiffer Norbert N Lackner Karl J KJ Bettecken Thomas T Meitinger Thomas T Oexle Konrad K Pirastu Mario M Portas Laura L Nag Abhishek A Williams Katie M KM Yonova-Doing Ekaterina E Klein Ronald R Klein Barbara E BE Hosseini S Mohsen SM Paterson Andrew D AD Makela Kari-Matti KM Lehtimaki Terho T Kahonen Mika M Raitakari Olli O Yoshimura Nagahisa N Matsuda Fumihiko F Chen Li Jia LJ Pang Chi Pui CP Yip Shea Ping SP Yap Maurice K H MK Meguro Akira A Mizuki Nobuhisa N Inoko Hidetoshi H Foster Paul J PJ Zhao Jing Hua JH Vithana Eranga E Tai E-Shyong ES Fan Qiao Q Xu Liang L Campbell Harry H Fleck Brian B Rudan Igor I Aung Tin T Hofman Albert A Uitterlinden André G AG Bencic Goran G Khor Chiea-Chuen CC Forward Hannah H Pärssinen Olavi O Mitchell Paul P Rivadeneira Fernando F Hewitt Alex W AW Williams Cathy C Oostra Ben A BA Teo Yik-Ying YY Hammond Christopher J CJ Stambolian Dwight D Mackey David A DA Klaver Caroline C W CC Wong Tien-Yin TY Saw Seang-Mei SM Baird Paul N PN

American journal of human genetics 20130801 2

Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2 ...[more]

PMID: 24144296

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Project description:Importance:Uncorrected refractive error (RE) is a leading cause of visual impairment, and variations in ocular anatomy determine RE. The unique ocular determinants of RE in Chinese American individuals have not been studied previously. Objective:To report ocular determinants of RE in a Chinese American population 50 years and older in Monterey Park, California. Design, Setting, and Participants:The Chinese American Eye Study, a population-based, cross-sectional study, was conducted from February 1, 2010, through October 31, 2013, in Monterey Park, with this particular data analysis performed from January 1 through December 31, 2016. This study included data from 4582 participants who underwent an eye examination to obtain axial length (AL), central corneal thickness, vitreous chamber depth (VCD), anterior chamber depth (ACD), lens thickness (LT), corneal power (CP), noncycloplegic subjective refraction, and lens nuclear opalescence (NOP) grading. Data from the right phakic eye of each participant were used. Multiple regression models (standardized regression coefficients [SRCs] and semipartial correlation coefficients squared [SPCCs2]) identified key determinants of RE. Main Outcomes and Measures:Ocular determinants of RE. Results:Among the 4071 participants eligible for analysis (1496 men [36.7%] and 2575 women [63.3%]; mean [SD] age, 60.5 [8.1] years), mean (SD) RE was -0.52 (2.95) diopters (D), with no sex-related difference. A hyperopic shift occurred in women from -0.62 (2.95) D at 50 to 59 years to 0.60 (1.62) D at 80 years or older and in men from -0.69 (3.00) D at 50 to 59 years to 0.40 (2.29) D at 80 years or older (P < .001 for both). Compared with men, women had shorter AL (mean [SD], 23.62 [1.34] vs 24.14 [1.27] mm; P = .006), shorter ACD (mean [SD], 3.33 [0.34] vs 3.44 [0.34] mm; P < .001), and steeper CP (mean [SD], 43.50 [1.52] vs 42.88 [1.45] D; P = .02), after adjusting for age and height. No sex differences were found in VCD, LT, and NOP after height adjustment. Compared with younger individuals, older individuals had shallower ACD, thicker LT, and more NOP compared with younger individuals (P < .001 for both), even after adjustment for height. Axial length was the strongest determinant of RE (SRC = -0.92; SPCC2 = 0.55), followed by CP (SRC = -0.43; SPCC2 = 0.15). When individual components of AL were evaluated, VCD had the greatest contributing effect (SRC = -0.99; SPCC2 = 0.52), followed by CP (SRC = -0.47; SPCC2 = 0.15) and LT (SRC = -0.29; SPCC2 = 0.06). Conclusions and Relevance:These data suggest that Chinese American individuals have longer AL and greater contribution of AL to RE than do Latino and other Chinese populations. Future studies should explore risk factors for increased AL in Chinese Americans and potential interventions that may ultimately prevent myopia-related disease.

Project description:Albinism is associated with a variety of ocular anomalies including refractive errors. The purpose of this study was to investigate the ocular development of an albino chick line. The ocular development of both albino and normally pigmented chicks was monitored using retinoscopy to measure refractive errors and high frequency A-scan ultrasonography to measure axial ocular dimensions. Functional tests included an optokinetic nystagmus paradigm to assess visual acuity, and flash ERGs to assess retinal function. The underlying genetic abnormality was characterized using a gene microarray, PCR and a tyrosinase assay. The ultrastructure of the retinal pigment epithelium (RPE) was examined using transmission electron microscopy. PCR confirmed that the genetic abnormality in this line is a deletion in exon 1 of the tyrosinase gene. Tyrosinase gene expression in isolated RPE cells was minimally detectable, and there was minimal enzyme activity in albino feather bulbs. The albino chicks had pink eyes and their eyes transilluminated, reflecting the lack of melanin in all ocular tissues. All three main components, anterior chamber, crystalline lens and vitreous chamber, showed axial expansion over time in both normal and albino animals, but the anterior chambers of albino chicks were consistently shallower than those of normal chicks, while in contrast, their vitreous chambers were longer. Albino chicks remained relatively myopic, with higher astigmatism than the normally pigmented chicks, even though both groups underwent developmental emmetropization. Albino chicks had reduced visual acuity yet the ERG a- and b-wave components had larger amplitudes and shorter than normal implicit times. Developmental emmetropization occurs in the albino chick but is impaired, likely because of functional abnormalities in the RPE and/or retina as well as optical factors. In very young chicks the underlying genetic mutation may also contribute to refractive error and eye shape abnormalities.

Dataset Information

Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.

Publications

Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.

Similar Datasets

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