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

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; P.J. Van der Spek; R. Haak; Hanne Meijers-Heijboer; Elisabeth M van Leeuwen; Sudha K Iyengar; J.H. Lass; A. Hofman; F. Rivadeneira; A.G. Uitterlinden; J.R. Vingerling; T. Lehtimaki; O.T. Raitakari; G. Biino; M.P. Concas; T.H. Schwantes-An; R.P. Igo; G. Cuellar-Partida; N.G. Martin; J.E. Craig; P. Gharahkhani; K.M. Williams; A. Naq; J.S. Rahi; P.M. Cumberland; C. Delcourt; C. Bellenquez; J.S. Ried; Arthur A Bergen; T. Meitinger; C. Gieger; T.Y. Wong; A.W. Hewitt; D.A. Mackey; C.L. Simpson; N. Pfeiffer; O. Parssinen; P.N. Baird; V. Vitart; N. Amin; C.M. Van Duijn; J.E. Bailey-Wilson; T.L. Young; S.M. Saw; D. Stambolian; S. MacGregor; J.A. Guggenheim; J.Y. Tung; C.J. Hammond; C.C.W. Klaver

doi:10.1038/s41588-018-0127-7

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

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 JonasYa 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, P.J. Van der Spek, R. Haak, Hanne Meijers-Heijboer, Elisabeth M van Leeuwen, Sudha K Iyengar, J.H. Lass, A. Hofman, F. Rivadeneira, A.G. Uitterlinden, J.R. Vingerling, T. Lehtimaki, O.T. Raitakari, G. Biino, M.P. Concas, T.H. Schwantes-An, R.P. Igo, G. Cuellar-Partida, N.G. Martin, J.E. Craig, P. Gharahkhani, K.M. Williams, A. Naq, J.S. Rahi, P.M. Cumberland, C. Delcourt, C. Bellenquez, J.S. Ried, Arthur A Bergen, T. Meitinger, C. Gieger, T.Y. Wong, A.W. Hewitt, D.A. Mackey, C.L. Simpson, N. Pfeiffer, O. Parssinen, P.N. Baird, V. Vitart, N. Amin, C.M. Van Duijn, J.E. Bailey-Wilson, T.L. Young, S.M. Saw, D. Stambolian, S. MacGregor, J.A. Guggenheim, J.Y. Tung, C.J. Hammond, C.C.W. Klaver

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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.

Originele taal-2	Engels
Pagina's (van-tot)	834-848
Aantal pagina's	15
Tijdschrift	Nature Genetics
Volume	50
Nummer van het tijdschrift	6
DOI's	https://doi.org/10.1038/s41588-018-0127-7
Status	Gepubliceerd - 2018

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Tedja, M. S., Wojciechowski, R., Hysi, P. G., Eriksson, N., Furlotte, N. A., Verhoeven, V. J. M., Iglesias, A. I., Meester-Smoor, M. A., Tompson, S. W., Fan, Q., Khawaja, A. P., Cheng, C.-Y., Höhn, R., Yamashiro, K., Wenocur, A., Grazal, C., Haller, T., Metspalu, A., Wedenoja, J., ... Klaver, C. C. W. (2018). Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error. Nature Genetics, 50(6), 834-848. https://doi.org/10.1038/s41588-018-0127-7

@article{67984a46b4c94c16818c32a0935f3046,

title = "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.",

keywords = "Journal Article",

author = "Tedja, {Milly S} and Robert Wojciechowski and Hysi, {Pirro G} and Nicholas Eriksson and Furlotte, {Nicholas A} and Verhoeven, {Virginie J M} and Iglesias, {Adriana I} and Meester-Smoor, {Magda A} and Tompson, {Stuart W} and Qiao Fan and Khawaja, {Anthony P} and Ching-Yu Cheng and Ren{\'e} H{\"o}hn and Kenji Yamashiro and Adam Wenocur and Clare Grazal and Toomas Haller and Andres Metspalu and Juho Wedenoja and Jonas, {Jost B} and Wang, {Ya Xing} and Jing Xie and Paul Mitchell and Foster, {Paul J} and Klein, {Barbara E K} and Ronald Klein and Paterson, {Andrew D} and Hosseini, {S Mohsen} and Shah, {Rupal L} and Cathy Williams and Yik-Ying Teo and Tham, {Yih Chung} and Preeti Gupta and Wanting Zhao and Yuan Shi and Woei-Yuh Saw and E-Shyong Tai and Sim, {Xue Ling} and Huffman, {Jennifer E} and Ozren Pola{\v s}ek and Caroline Hayward and Goran Bencic and Igor Rudan and Wilson, {James F} and Joshi, {Peter K} and Akitaka Tsujikawa and Fumihiko Matsuda and Whisenhunt, {Kristina N} and Tanja Zeller and {Van der Spek}, P.J. and R. Haak and Hanne Meijers-Heijboer and {van Leeuwen}, {Elisabeth M} and Iyengar, {Sudha K} and J.H. Lass and A. Hofman and F. Rivadeneira and A.G. Uitterlinden and J.R. Vingerling and T. Lehtimaki and O.T. Raitakari and G. Biino and M.P. Concas and T.H. Schwantes-An and R.P. Igo and G. Cuellar-Partida and N.G. Martin and J.E. Craig and P. Gharahkhani and K.M. Williams and A. Naq and J.S. Rahi and P.M. Cumberland and C. Delcourt and C. Bellenquez and J.S. Ried and Bergen, {Arthur A} and T. Meitinger and C. Gieger and T.Y. Wong and A.W. Hewitt and D.A. Mackey and C.L. Simpson and N. Pfeiffer and O. Parssinen and P.N. Baird and V. Vitart and N. Amin and {Van Duijn}, C.M. and J.E. Bailey-Wilson and T.L. Young and S.M. Saw and D. Stambolian and S. MacGregor and J.A. Guggenheim and J.Y. Tung and C.J. Hammond and C.C.W. Klaver",

year = "2018",

doi = "10.1038/s41588-018-0127-7",

language = "English",

volume = "50",

pages = "834--848",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "6",

}

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, Y-Y, 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, 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, Lehtimaki, T, Raitakari, OT, Biino, G, Concas, MP, Schwantes-An, TH, Igo, RP, Cuellar-Partida, G, Martin, NG, Craig, JE, Gharahkhani, P, Williams, KM, Naq, A, Rahi, JS, Cumberland, PM, Delcourt, C, Bellenquez, C, Ried, JS, Bergen, AA, Meitinger, T, Gieger, C, Wong, TY, Hewitt, AW, Mackey, DA, Simpson, CL, Pfeiffer, N, Parssinen, O, Baird, PN, Vitart, V, Amin, N, Van Duijn, CM, Bailey-Wilson, JE, Young, TL, Saw, SM, Stambolian, D, MacGregor, S, Guggenheim, JA, Tung, JY & Hammond, CJ & Klaver, CCW 2018, 'Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error', Nature Genetics, vol. 50, nr. 6, blz. 834-848. https://doi.org/10.1038/s41588-018-0127-7

TY - JOUR

T1 - Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error

AU - Tedja, Milly S

AU - Wojciechowski, Robert

AU - Hysi, Pirro G

AU - Eriksson, Nicholas

AU - Furlotte, Nicholas A

AU - Verhoeven, Virginie J M

AU - Iglesias, Adriana I

AU - Meester-Smoor, Magda A

AU - Tompson, Stuart W

AU - Fan, Qiao

AU - Khawaja, Anthony P

AU - Cheng, Ching-Yu

AU - Höhn, René

AU - Yamashiro, Kenji

AU - Wenocur, Adam

AU - Grazal, Clare

AU - Haller, Toomas

AU - Metspalu, Andres

AU - Wedenoja, Juho

AU - Jonas, Jost B

AU - Wang, Ya Xing

AU - Xie, Jing

AU - Mitchell, Paul

AU - Foster, Paul J

AU - Klein, Barbara E K

AU - Klein, Ronald

AU - Paterson, Andrew D

AU - Hosseini, S Mohsen

AU - Shah, Rupal L

AU - Williams, Cathy

AU - Teo, Yik-Ying

AU - Tham, Yih Chung

AU - Gupta, Preeti

AU - Zhao, Wanting

AU - Shi, Yuan

AU - Saw, Woei-Yuh

AU - Tai, E-Shyong

AU - Sim, Xue Ling

AU - Huffman, Jennifer E

AU - Polašek, Ozren

AU - Hayward, Caroline

AU - Bencic, Goran

AU - Rudan, Igor

AU - Wilson, James F

AU - Joshi, Peter K

AU - Tsujikawa, Akitaka

AU - Matsuda, Fumihiko

AU - Whisenhunt, Kristina N

AU - Zeller, Tanja

AU - Van der Spek, P.J.

AU - Haak, R.

AU - Meijers-Heijboer, Hanne

AU - van Leeuwen, Elisabeth M

AU - Iyengar, Sudha K

AU - Lass, J.H.

AU - Hofman, A.

AU - Rivadeneira, F.

AU - Uitterlinden, A.G.

AU - Vingerling, J.R.

AU - Lehtimaki, T.

AU - Raitakari, O.T.

AU - Biino, G.

AU - Concas, M.P.

AU - Schwantes-An, T.H.

AU - Igo, R.P.

AU - Cuellar-Partida, G.

AU - Martin, N.G.

AU - Craig, J.E.

AU - Gharahkhani, P.

AU - Williams, K.M.

AU - Naq, A.

AU - Rahi, J.S.

AU - Cumberland, P.M.

AU - Delcourt, C.

AU - Bellenquez, C.

AU - Ried, J.S.

AU - Bergen, Arthur A

AU - Meitinger, T.

AU - Gieger, C.

AU - Wong, T.Y.

AU - Hewitt, A.W.

AU - Mackey, D.A.

AU - Simpson, C.L.

AU - Pfeiffer, N.

AU - Parssinen, O.

AU - Baird, P.N.

AU - Vitart, V.

AU - Amin, N.

AU - Van Duijn, C.M.

AU - Bailey-Wilson, J.E.

AU - Young, T.L.

AU - Saw, S.M.

AU - Stambolian, D.

AU - MacGregor, S.

AU - Guggenheim, J.A.

AU - Tung, J.Y.

AU - Hammond, C.J.

AU - Klaver, C.C.W.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/s41588-018-0127-7

DO - 10.1038/s41588-018-0127-7

M3 - Article

C2 - 29808027

SN - 1061-4036

VL - 50

SP - 834

EP - 848

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -

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

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