Unknown

Dataset Information

0

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

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.

SUBMITTER: Tedja MS 

PROVIDER: S-EPMC5980758 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

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

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

Nature genetics 20180528 6

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  ...[more]

Similar Datasets

Unknown Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium.
| S-EPMC4291519 | biostudies-literature
Unknown Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error.
| S-EPMC7081241 | biostudies-literature
Unknown A genome-wide association study for myopia and refractive error identifies a susceptibility locus at 15q25.
| S-EPMC4115148 | biostudies-literature
Unknown Genome-wide association studies of refractive error and myopia, lessons learned, and implications for the future.
| S-EPMC4039381 | biostudies-literature
Unknown Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia.
| S-EPMC3740568 | biostudies-literature
Unknown Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error.
| S-EPMC4820539 | biostudies-literature
Unknown Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.
| S-EPMC3772747 | biostudies-literature
Unknown Meta-analysis of genome-wide association studies in five cohorts reveals common variants in RBFOX1, a regulator of tissue-specific splicing, associated with refractive error.
| S-EPMC3674806 | biostudies-literature
Unknown Common mechanisms underlying refractive error identified in functional analysis of gene lists from genome-wide association study results in 2 European British cohorts.
| S-EPMC4041328 | biostudies-literature
Unknown Pathway analysis of breast cancer genome-wide association study highlights three pathways and one canonical signaling cascade.
| S-EPMC2907250 | biostudies-literature