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Genome wide association meta analysis highlights light induced signaling as a driver for refractive error


Tedja, MS and Wojciechowski, R and Hysi, PG and Eriksson, N and Furlotte, NA and Verhoeven, VJM and Iglesias, AI and Meester-Smoor, MA and Tompson, SW and Fan, Q and Khawaja, AP and Cheng, CY and Hohn, R and Yamashiro, K and Wenocur, A and Grazal, C and Haller, T and Metspalu, A and Wedenoja, J and Jonas, JB and Wang, YX and Xie, J and Mitchell, P and Foster, PJ and Klein, BEK and Klein, R and Paterson, AD and Hosseini, SM and Shah, RL and Williams, C and Teo, YY and Tham, YC and Gupta, P and Zhao, W and Shi, Y and Saw, WY and Tai, ES and Sim, XL and Huffman, JE and Polasek, O and Hayward, C and Bencic, G and Rudan, I and Wilson, JF and Joshi, PK and Tsujikawa, A and Matsuda, F and Whisenhunt, KN and van der Spek, P and Haak, R and Meijers-Heijboer, H and van Leeuwen, EM and Iyengar, SK and Lass, JH and Hoffman, A and Rivadeneira, F and Uitterlinden, AG and V, JR and Lehtimaki, T and Raitakari, OT and Biino, G and Concas, MP and Haarman, AEG and Schwantes-An, TH and Igo JR, RP and Cuellar-Partida, G and Jhanji, V and Martin, NG and Craig, JE and Gharahkhani, P and Williams, KM and Nag, A and Rahi, JS and Cumberland, PM and Delcourt, C and Bellenguez, C and Ried, JS and Bergen, AA and Meitinger, T and Gieger, C and Wong, TY and Hewitt, AW and Mackey, DA and Simpson, NP and Parssinen, O and Baird, PN and Vitart, Vi and Amin, N and van Duijn, CM and Bailey-Wilson, JE and Saw, SM and Stambolian, D and MacGregor, S and Guggenheim, JA and Tung, JY and Hammond, CJ and Klaver, CWC, CREAM Consortium, 23andMe Research Team, UK Biobank Eye and Vision Consortium, Genome wide association meta analysis highlights light induced signaling as a driver for refractive error, Nature Genetics, 50, (6) pp. 834-848. ISSN 1061-4036 (2018) [Refereed Article]

DOI: doi:10.1038/s41588-018-0127-7


Refractive errors, including myopia, are the most frequent eye disorders worldwide and an increasingly common cause of blindness. This genome-wide association meta-analysis in 160,420 participants and replication in 95,505 participants increased the number of established independent signals from 37 to 161 and showed high genetic correlation between Europeans and Asians (>0.78). Expression experiments and comprehensive in silico analyses identified retinal cell physiology and light processing as prominent mechanisms, and also identified functional contributions to refractive-error development in all cell types of the neurosensory retina, retinal pigment epithelium, vascular endothelium and extracellular matrix. Newly identified genes implicate novel mechanisms such as rod-and-cone bipolar synaptic neurotransmission, anterior-segment morphology and angiogenesis. Thirty-one loci resided in or near regions transcribing small RNAs, thus suggesting a role for post-transcriptional regulation. Our results support the notion that refractive errors are caused by a light-dependent retina-to-sclera signaling cascade and delineate potential pathobiological molecular drivers.

Item Details

Item Type:Refereed Article
Keywords:high grade myopia, retinal pigment epithelium, serotonin pathway genes, form deprivation myopia, common variants, ocular growth, retinitis pigmentosa, genotype imputation, missense mutations, dopamine receptors
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Cell and nuclear division
Objective Division:Health
Objective Group:Clinical health
Objective Field:Treatment of human diseases and conditions
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
UTAS Author:Mackey, DA (Professor David Mackey)
ID Code:152778
Year Published:2018
Web of Science® Times Cited:137
Deposited By:Medicine
Deposited On:2022-08-24
Last Modified:2022-09-07

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