Dataset Information

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

ACCESS DATA

Publications

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

Similar Datasets

Project description:The purpose of this study was to develop a method of estimating pulsatile ocular blood volume (POBV) from measurements taken during an ophthalmic exam, including axial length and using a tonometer capable of measuring intraocular pressure (IOP) and ocular pulse amplitude (OPA). Unpublished OPA data from a previous invasive study was used in the derivation, along with central corneal thickness (CCT) and axial length (AL), as well as IOP from the PASCAL dynamic contour tonometer (DCT) and intracameral (ICM) measurements of IOP for 60 cataract patients. Intracameral mean pressure was set to 15, 20, and 35 mmHg (randomized sequence) in the supine position, using a fluid-filled manometer. IOP and OPA measurements were acquired at each manometric setpoint (DCT and ICM simultaneously). In the current study, ocular rigidity (OR) was estimated using a published significant relationship of OR to the natural log of AL in which OR was invasively measured through fluid injection. Friedenwald's original pressure volume relationship was then used to derive the estimated POBV, delivered to the choroid with each heartbeat as a function of OR, systolic IOP (IOPsys), diastolic IOP (IOPdia), and OPA, according to the derived equation POBV = log (IOPsys/IOPdia) / OR. Linear regression analyses were performed comparing OPA to OR and calculated POBV at each of the three manometric setpoints. POBV was also compared to OPA/IOPdia with all data points combined. Significance threshold was p < 0.05. OR estimated from AL showed a significant positive relationship to OPA for both DCT (p < 0.011) and ICM (p < 0.006) at all three manometric pressure setpoints, with a greater slope for lower IOP. Calculated POBV also showed a significant positive relationship to OPA (p < 0.001) at all three setpoints with greater slope at lower IOP, and a significant negative relationship with IOPdia. In the combined analysis, POBV showed a significant positive relationship to OPA/ IOPdia (p < 0.001) in both ICM and DCT measurements with R2 = 0.9685, and R2 = 0.9589, respectively. POBV provides a straight-forward, clinically applicable method to estimate ocular blood supply noninvasively. Higher IOP in combination with lower OPA results in the lowest values of POBV. The simplified ratio, OPA/ IOPdia, may also provide a useful clinical tool for evaluating changes in ocular blood supply in diseases with a vascular component, such as diabetic retinopathy and normal tension glaucoma. Future studies are warranted.

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

OmicsDI is part of the ELIXIR infrastructure

Tweets