Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-06

AUTHORS

Milly S. Tedja, Robert Wojciechowski, Pirro G. Hysi, Nicholas Eriksson, Nicholas A. Furlotte, Virginie J.M. Verhoeven, Adriana I. Iglesias, Magda A. Meester-Smoor, Stuart W. Tompson, Qiao Fan, Anthony P. Khawaja, Ching-Yu Cheng, René Höhn, Kenji Yamashiro, Adam Wenocur, Clare Grazal, Toomas Haller, Andres Metspalu, Juho Wedenoja, Jost B. Jonas, Ya Xing Wang, Jing Xie, Paul Mitchell, Paul J. Foster, Barbara E.K. Klein, Ronald Klein, Andrew D. Paterson, S. Mohsen Hosseini, Rupal L. Shah, Cathy Williams, Yik Ying Teo, Yih Chung Tham, Preeti Gupta, Wanting Zhao, Yuan Shi, Woei-Yuh Saw, E-Shyong Tai, Xue Ling Sim, Jennifer E. Huffman, Ozren Polašek, Caroline Hayward, Goran Bencic, Igor Rudan, James F. Wilson, , , , Peter K. Joshi, Akitaka Tsujikawa, Fumihiko Matsuda, Kristina N. Whisenhunt, Tanja Zeller, Peter J. van der Spek, Roxanna Haak, Hanne Meijers-Heijboer, Elisabeth M. van Leeuwen, Sudha K. Iyengar, Jonathan H. Lass, Albert Hofman, Fernando Rivadeneira, André G. Uitterlinden, Johannes R. Vingerling, Terho Lehtimäki, Olli T. Raitakari, Ginevra Biino, Maria Pina Concas, Tae-Hwi Schwantes-An, Robert P. Igo, Gabriel Cuellar-Partida, Nicholas G. Martin, Jamie E. Craig, Puya Gharahkhani, Katie M. Williams, Abhishek Nag, Jugnoo S. Rahi, Phillippa M. Cumberland, Cécile Delcourt, Céline Bellenguez, Janina S. Ried, Arthur A. Bergen, Thomas Meitinger, Christian Gieger, Tien Yin Wong, Alex W. Hewitt, David A. Mackey, Claire L. Simpson, Norbert Pfeiffer, Olavi Pärssinen, Paul N. Baird, Veronique Vitart, Najaf Amin, Cornelia M. van Duijn, Joan E. Bailey-Wilson, Terri L. Young, Seang-Mei Saw, Dwight Stambolian, Stuart MacGregor, Jeremy A. Guggenheim, Joyce Y. Tung, Christopher J. Hammond, Caroline C.W. Klaver

ABSTRACT

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. More... »

PAGES

834-848

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-018-0127-7

    DOI

    http://dx.doi.org/10.1038/s41588-018-0127-7

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1104216233

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29808027


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