| Title: |
Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error |
| Authors: |
Tedja, MS; Wojciechowski, R; Hysi, PG; Eriksson, N; Furlotte, NA; Verhoeven, VJM; Iglesias, AI; Meester-Smoor, MA; Tompson, SW; Fan, Q; Khawaja, AP; Cheng, C-Y; Höhn, R; Yamashiro, K; Wenocur, A; Grazal, C; Haller, T; Metspalu, A; Wedenoja, J; Jonas, JB; Wang, YX; Xie, J; Mitchell, P; Foster, PJ; Klein, BEK; Klein, R; Paterson, AD; Hosseini, SM; Shah, RL; Williams, C; Teo, YY; Tham, YC; Gupta, P; Zhao, W; Shi, Y; Saw, W-Y; Tai, E-S; Sim, XL; Huffman, JE; Polašek, O; Hayward, C; Bencic, G; Rudan, I; Wilson, JF; Consortium, Cream; Team, 23Andme Research; Consortium, Uk Biobank Eye And Vision; Joshi, PK; Tsujikawa, A; Matsuda, F; Whisenhunt, KN; Zeller, T; Van Der Spek, PJ; Haak, R; Meijers-Heijboer, H; Van Leeuwen, EM; Iyengar, SK; Lass, JH; Hofman, A; Rivadeneira, F; Uitterlinden, AG; Vingerling, JR; Lehtimäki, T; Raitakari, OT; Biino, G; Concas, MP; Schwantes-An, T-H; Igo, RP; Cuellar-Partida, G; Martin, NG; Craig, JE; Gharahkhani, P; Williams, KM; Nag, A; Rahi, JS; Cumberland, PM; Delcourt, C; Bellenguez, C; Ried, JS; Bergen, AA; Meitinger, T; Gieger, C; Wong, TY; Hewitt, AW; Mackey, DA; Simpson, CL; Pfeiffer, N; Pärssinen, O; Baird, PN; Vitart, V; Amin, N; Van Duijn, CM; Bailey-Wilson, JE; Young, TL; Saw, S-M; Stambolian, D; Macgregor, S; Guggenheim, JA; Tung, JY; Hammond, CJ; Klaver, CCW |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2018 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1038/s41588-018-0127-7 |
| Availability: |
https://doi.org/10.1038/s41588-018-0127-7; https://ora.ox.ac.uk/objects/uuid:1b7bed67-172e-4066-a18b-8a4af318836b |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.8FE1F0D6 |
| Database: |
BASE |