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1. Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future

Author

Colijn, J.M. (Johanna), Buitendijk, G.H.S. (Gabrielle), Prokofyeva, E. (Elena), Alves, D. (Dalila), Cachulo, M.L. (Maria L.), Khawaja, A.P. (Anthony), Cougnard-Grégoire, A. (Audrey), Merle, B.M.J. (Bénédicte M.J.), Korb, C. (Christina), Erke, M.G. (Maja Gran), Bron, A. (Alain), Anastasopoulos, E. (Eleftherios), Meester-Smoor, M.A. (Magda), Segato, T. (Tatiana), Piermarocchi, S. (Stefano), Jong, P.T.V.M. (Paulus) de, Vingerling, J.R. (Hans), Topouzis, F. (Fotis), Creuzot-Garcher, C. (Catherine), Bertelsen, G. (Geir), Pfeiffer, A.F.H. (Andreas), Fletcher, A.E. (Astrid E.), Foster, P.J. (Paul), Silva, R. (Rufino), Korobelnik, J.-F. (Jean-François), Delcourt, C. (Cécile), Klaver, C.C.W. (Caroline), Ajana, S. (Soufiane), Arango-Gonzalez, B. (Blanca), Arndt, V. (Verena), Bhatia, V. (Vaibhav), Bhattacharya, S.S. (Shomi S.), Biarnés, M. (Marc), Borrell, A. (Anna), Bühren, S. (Sebastian), Calado, S.M. (Sofia M.), Colijn, J.M. (Johanna M.), Dammeier, S. (Sascha), Jong, E.K. (Eiko) de, De la Cerda, B. (Berta), den Hollander, A.I. (Anneke I.), Diaz-Corrales, F.J. (Francisco J.), Diether, S. (Sigrid), Emri, E. (Eszter), Endermann, T. (Tanja), Ferraro, L.L. (Lucia L.), Garcia, M. (Míriam), Heesterbeek, T.J. (Thomas J.), Honisch, S. (Sabina), Hoyng, C.B. (Carel B.), Kersten, E. (Eveline), Kilger, E. (Ellen), Klaver, C.C.W. (Caroline C.W.), Langen, H. (Hanno), Lengyel, I. (Imre), Luthert, P. (Phil), Maugeais, C. (Cyrille), Meester-Smoor, M. (Magda), Monés, J. (Jordi), Nogoceke, E. (Everson), Peto, T. (Tunde), Pool, F.M. (Frances M.), Rodríguez, E. (Eduardo), Ueffing, M. (Marius), Ulrich Bartz-Schmidt, K.U. (Karl U.), van Leeuwen, E.M. (Elisabeth M.), Verzijden, T. (Timo), Zumbansen, M. (Markus), Acar, N. (Niyazi), Anastosopoulos, E. (Eleftherios), Azuara-Blanco, A. (Augusto), Bergen, A.A.B. (Arthur), Binquet, C. (Christine), Bird, A.C. (Alan), Bretillon, L. (Lionel), Buitendijk, G. (Gabrielle), Cachulo, M.L. (Maria Luz), Chakravarthy, U. (Usha), Chan, M. (Michelle), Chang, P. (Petrus), Colijn, J. (Johanna), Cumberland, P. (Phillippa), Cunha-Vaz, J. (José), Daien, V. (Vincent), Deak, G. (Gabor), Delyfer, M.-N. (Marie-Noëlle), Hollander, A.I. (Anneke), Dietzel, M. (Martha), Fauser, S. (Sascha), Finger, R. (Robert), Fletcher, A. (Astrid), Foster, P.J. (Paul J.), Founti, P. (Panayiota), Göbel, A. (Arno), Gorgels, T.G.M.F. (Theo), Grauslund, J. (Jakob), Grus, F. (Franz), Hammond, C.J. (Christopher), Helmer, C. (Catherine), Hense, H.-W. (Hans-Werner), Hermann, M. (Manuel), Hoehn, R. (René), Hogg, R. (Ruth), Holz, F.G. (Frank), Hoyng, C.B. (Carel), Jansonius, N.M. (Nomdo), Janssen, S.F. (Sarah), Khawaja, A. (Anthony), Lamparter, J. (Julia), Le Goff, M. (Mélanie), Leal, S. (Sergio), Lechanteur, Y.T.E. (Yara T. E.), Lehtimäki, T. (Terho), Lotery, A.J. (Andrew), Leung, I. (Irene), Mauschitz, M. (Matthias), Merle, B. (Bénédicte), Meyer zu Westrup, V. (Verena), Midena, E. (Edoardo), Miotto, S. (Stefania), Mirshahi, A. (Alireza), Mohan-Saïd, S. (Sadek), Mueller, M. (Michael), Muldrew, A. (Alyson), Nunes, S. (Sandrina), Oexle, K. (Konrad), Peto, T. (Tünde), Rahi, J. (Jugnoo), Raitakari, O. (Olli), Ribeiro, L. (Luisa), Rougier, M.-B. (Marie-Bénédicte), Sahel, J.-A. (José-Alain), Salonikiou, A. (Aggeliki), Sanchez, C. (Clarisa), Schmitz-Valckenberg, S. (Steffen), Schweitzer, C.M.C. (C. M C), Shehata, J. (Jasmin), Silvestri, G. (Giuliana), Simader, C. (Christian), Souied, E.H. (Eric), Springelkamp, H. (Henriët), Tapp, R. (Robyn), Verhoeven, V. (Virginie), Von Hanno, T. (Therese), Vujosevic, S. (Stela), Williams, K. (Katie), Wolfram, C. (Christian), Yip, J. (Jennifer), Zerbib, J. (Jennyfer), Zwiener, I. (Isabella), Colijn, J.M. (Johanna), Buitendijk, G.H.S. (Gabrielle), Prokofyeva, E. (Elena), Alves, D. (Dalila), Cachulo, M.L. (Maria L.), Khawaja, A.P. (Anthony), Cougnard-Grégoire, A. (Audrey), Merle, B.M.J. (Bénédicte M.J.), Korb, C. (Christina), Erke, M.G. (Maja Gran), Bron, A. (Alain), Anastasopoulos, E. (Eleftherios), Meester-Smoor, M.A. (Magda), Segato, T. (Tatiana), Piermarocchi, S. (Stefano), Jong, P.T.V.M. (Paulus) de, Vingerling, J.R. (Hans), Topouzis, F. (Fotis), Creuzot-Garcher, C. (Catherine), Bertelsen, G. (Geir), Pfeiffer, A.F.H. (Andreas), Fletcher, A.E. (Astrid E.), Foster, P.J. (Paul), Silva, R. (Rufino), Korobelnik, J.-F. (Jean-François), Delcourt, C. (Cécile), Klaver, C.C.W. (Caroline), Ajana, S. (Soufiane), Arango-Gonzalez, B. (Blanca), Arndt, V. (Verena), Bhatia, V. (Vaibhav), Bhattacharya, S.S. (Shomi S.), Biarnés, M. (Marc), Borrell, A. (Anna), Bühren, S. (Sebastian), Calado, S.M. (Sofia M.), Colijn, J.M. (Johanna M.), Dammeier, S. (Sascha), Jong, E.K. (Eiko) de, De la Cerda, B. (Berta), den Hollander, A.I. (Anneke I.), Diaz-Corrales, F.J. (Francisco J.), Diether, S. (Sigrid), Emri, E. (Eszter), Endermann, T. (Tanja), Ferraro, L.L. (Lucia L.), Garcia, M. (Míriam), Heesterbeek, T.J. (Thomas J.), Honisch, S. (Sabina), Hoyng, C.B. (Carel B.), Kersten, E. (Eveline), Kilger, E. (Ellen), Klaver, C.C.W. (Caroline C.W.), Langen, H. (Hanno), Lengyel, I. (Imre), Luthert, P. (Phil), Maugeais, C. (Cyrille), Meester-Smoor, M. (Magda), Monés, J. (Jordi), Nogoceke, E. (Everson), Peto, T. (Tunde), Pool, F.M. (Frances M.), Rodríguez, E. (Eduardo), Ueffing, M. (Marius), Ulrich Bartz-Schmidt, K.U. (Karl U.), van Leeuwen, E.M. (Elisabeth M.), Verzijden, T. (Timo), Zumbansen, M. (Markus), Acar, N. (Niyazi), Anastosopoulos, E. (Eleftherios), Azuara-Blanco, A. (Augusto), Bergen, A.A.B. (Arthur), Binquet, C. (Christine), Bird, A.C. (Alan), Bretillon, L. (Lionel), Buitendijk, G. (Gabrielle), Cachulo, M.L. (Maria Luz), Chakravarthy, U. (Usha), Chan, M. (Michelle), Chang, P. (Petrus), Colijn, J. (Johanna), Cumberland, P. (Phillippa), Cunha-Vaz, J. (José), Daien, V. (Vincent), Deak, G. (Gabor), Delyfer, M.-N. (Marie-Noëlle), Hollander, A.I. (Anneke), Dietzel, M. (Martha), Fauser, S. (Sascha), Finger, R. (Robert), Fletcher, A. (Astrid), Foster, P.J. (Paul J.), Founti, P. (Panayiota), Göbel, A. (Arno), Gorgels, T.G.M.F. (Theo), Grauslund, J. (Jakob), Grus, F. (Franz), Hammond, C.J. (Christopher), Helmer, C. (Catherine), Hense, H.-W. (Hans-Werner), Hermann, M. (Manuel), Hoehn, R. (René), Hogg, R. (Ruth), Holz, F.G. (Frank), Hoyng, C.B. (Carel), Jansonius, N.M. (Nomdo), Janssen, S.F. (Sarah), Khawaja, A. (Anthony), Lamparter, J. (Julia), Le Goff, M. (Mélanie), Leal, S. (Sergio), Lechanteur, Y.T.E. (Yara T. E.), Lehtimäki, T. (Terho), Lotery, A.J. (Andrew), Leung, I. (Irene), Mauschitz, M. (Matthias), Merle, B. (Bénédicte), Meyer zu Westrup, V. (Verena), Midena, E. (Edoardo), Miotto, S. (Stefania), Mirshahi, A. (Alireza), Mohan-Saïd, S. (Sadek), Mueller, M. (Michael), Muldrew, A. (Alyson), Nunes, S. (Sandrina), Oexle, K. (Konrad), Peto, T. (Tünde), Rahi, J. (Jugnoo), Raitakari, O. (Olli), Ribeiro, L. (Luisa), Rougier, M.-B. (Marie-Bénédicte), Sahel, J.-A. (José-Alain), Salonikiou, A. (Aggeliki), Sanchez, C. (Clarisa), Schmitz-Valckenberg, S. (Steffen), Schweitzer, C.M.C. (C. M C), Shehata, J. (Jasmin), Silvestri, G. (Giuliana), Simader, C. (Christian), Souied, E.H. (Eric), Springelkamp, H. (Henriët), Tapp, R. (Robyn), Verhoeven, V. (Virginie), Von Hanno, T. (Therese), Vujosevic, S. (Stela), Williams, K. (Katie), Wolfram, C. (Christian), Yip, J. (Jennifer), Zerbib, J. (Jennyfer), and Zwiener, I. (Isabella)

Abstract

Purpose Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design Meta-analysis of prevalence data. Participants A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures Prevalence of early and late AMD, BCVA, and number of AMD cases. Results Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95% C

Published
2017
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2. Associations with intraocular pressure across Europe: The European Eye Epidemiology (E3) Consortium

Author

Khawaja, A.P. (Anthony), Springelkamp, H. (Henriët), Creuzot-Garcher, C. (Catherine), Delcourt, C. (Cécile), Hofman, A. (Albert), Höhn, R. (René), Iglesias González, A.I. (Adriana), Wolfs, R.C.W. (Roger), Korobelnik, J.-F. (Jean-François), Silva, R. (Rufino), Topouzis, F. (Fotis), Williams, K.M. (Katie M.), Bron, A. (Alain), Buitendijk, G.H.S. (Gabrielle), Cachulo, M.L. (Maria da Luz), Cougnard-Grégoire, A. (Audrey), Dartigues, J.-F., Hammond, C.J. (Christopher J.), Pfeiffer, A.F.H. (Andreas), Salonikiou, A. (Angeliki), van Duijn, C.M. (Cornelia M.), Vingerling, J.R. (Hans), Luben, R.N. (Robert), Mirshahi, A. (Alireza), Lamparter, J. (Julia), Klaver, C.C.W. (Caroline), Jansonius, N.M. (Nomdo M.), Foster, P.J. (Paul), Khawaja, A.P. (Anthony), Springelkamp, H. (Henriët), Creuzot-Garcher, C. (Catherine), Delcourt, C. (Cécile), Hofman, A. (Albert), Höhn, R. (René), Iglesias González, A.I. (Adriana), Wolfs, R.C.W. (Roger), Korobelnik, J.-F. (Jean-François), Silva, R. (Rufino), Topouzis, F. (Fotis), Williams, K.M. (Katie M.), Bron, A. (Alain), Buitendijk, G.H.S. (Gabrielle), Cachulo, M.L. (Maria da Luz), Cougnard-Grégoire, A. (Audrey), Dartigues, J.-F., Hammond, C.J. (Christopher J.), Pfeiffer, A.F.H. (Andreas), Salonikiou, A. (Angeliki), van Duijn, C.M. (Cornelia M.), Vingerling, J.R. (Hans), Luben, R.N. (Robert), Mirshahi, A. (Alireza), Lamparter, J. (Julia), Klaver, C.C.W. (Caroline), Jansonius, N.M. (Nomdo M.), and Foster, P.J. (Paul)

Abstract

Raised intraocular pressure (IOP) is the most important risk factor for developing glaucoma, the second commonest cause of blindness globally. Understanding associations with IOP and variations in IOP between countries may teach us about mechanisms underlying glaucoma. We examined cross-sectional associations with IOP in 43,500 European adults from 12 cohort studies belonging to the European Eye Epidemiology (E3) consortium. Each study conducted multivariable linear regression with IOP as the outcome variable and results were pooled using random effects meta-analysis. The association of standardized study IOP with latitude was tested using meta-regression. Higher IOP was observed in men (0.18 mmHg; 95 % CI 0.06, 0.31; P = 0.004) and with higher body mass index (0.21 mmHg per 5 kg/m2; 95 % CI 0.14, 0.28; P < 0.001), shorter height (−0.17 mmHg per 10 cm; 95 % CI –0.25, −0.08; P < 0.001), higher systolic blood pressure (0.17 mmHg per 10 mmHg; 95 % CI 0.12, 0.22; P < 0.001) and more myopic refraction (0.06 mmHg per Dioptre; 95 % CI 0.03, 0.09; P < 0.001). An inverted U-shaped trend was observed between age and IOP, with IOP increasing up to the age of 60 and decreasing in participants older than 70 years. We found no significant association between standardized IOP and study location latitude (P = 0.76). Novel findings of our study include the association of lower IOP in taller people and an inverted-U shaped association of IOP with age. We found no evidence of significant variation in IOP across Europe. Despite the limited range of latitude amongst included studies, this finding is in favour of collaborative pooling of data from studies examining environmental and genetic determinants of IOP in Europeans.

Published
2016
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3. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

Author

Fan, Q. (Qiao), Verhoeven, V.J.M. (Virginie), Wojciechowski, R. (Robert), Barathi, V.A. (Veluchamy), Hysi, P.G. (Pirro), Guggenheim, J. (Jean), Höhn, R. (René), Vitart, V. (Veronique), Khawaja, A.P. (Anthony P.), Yamashiro, K. (Kenji), Hosseini, S.M. (S Mohsen), Lehtimäki, T. (Terho), Lu, Y. (Yi), Haller, T. (Toomas), Xie, J. (Jing), Delcourt, C. (Cécile), Pirastu, M. (Mario), Wedenoja, J. (Juho), Gharahkhani, P. (Puya), Venturini, C. (Cristina), Miyake, M. (Masahiro), Hewit, A.W. (Alex), Guo, X. (Xiaobo), Mazur, J. (Johanna), Huffman, J.E. (Jenifer E.), Williams, K.M. (Katie M.), Polasek, O. (Ozren), Campbell, H. (Harry), Rudan, I. (Igor), Vatavuk, Z. (Zoran), Wilson, J.F. (James F), Joshi, P.K. (Peter), Mcmahon, G. (George), St Pourcain, B. (Beate), Evans, D.M. (David), Simpson, C.L. (Claire), Schwantes-An, T.-H. (Tae-Hwi), Igo Jr., R.P. (Robert), Mirshahi, A. (Alireza), Cougnard-Grégoire, A. (Audrey), Bellenguez, C. (Céline), Blettner, M. (Maria), Raitakari, O. (Olli), Kähönen, M. (Mika), Seppälä, I. (Ilkka), Zeller, T. (Tanja), Meitinger, T. (Thomas), Ried, J.S. (Janina), Gieger, C. (Christian), Portas, L. (Laura), Leeuwen, E.M. (Elisa) van, Amin, N. (Najaf), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Vingerling, J.R. (Hans), Wang, Y. (Ying), Wang, X. (Xu), Tai-Hui Boh, E. (Eileen), Ikram, M.K. (Kamran), Sabanayagam, C. (Charumathi), Gupta, P. (Preeti), Tan, V. (Vincent), Zhou, L. (Lei), Ho, C.E.H. (Candice E. H.), Lim, W. (Wan'E), Beuerman, R.W. (Roger W.), Siantar, R. (Rosalynn), Tai, E.-S. (E-Shyong), Vithana, E.N. (Eranga), Mihailov, E. (Evelin), Khor, C.C., Hayward, C. (Caroline), Luben, R.N. (Robert), Foster, P.J. (Paul), Klein, B.E.K. (Barbara), Klein, R. (Ronald), Wong, H.-S. (Hoi-Suen), Mitchell, P. (Paul), Metspalu, A. (Andres), Aung, T. (Tin), Young, T.L. (Terri L.), He, M. (Mingguang), Pärssinen, O. (Olavi), Duijn, C.M. (Cornelia) van, Jin Wang, J. (Jie), Williams, C. (Cathy), Jonas, J.B. (Jost B.), Teo, Y.Y. (Yik Ying), Mackey, D.A. (David), Oexle, K. (Konrad), Yoshimura, N., Paterson, A.D. (Andrew D.), Pfeiffer, N. (Norbert), Wong, T.Y. (Tien Yin), Baird, P.N. (Paul), Stambolian, D. (Dwight), Wilson, J.E.B. (Joan E. Bailey), Cheng, C-Y. (Ching-Yu), Hammond, C.J. (Christopher J.), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Rahi, J.S. (Jugnoo), Korobelnik, J.-F. (Jean-François), Kemp, J.P. (John), Timpson, N.J. (Nicholas), Smith, A.V. (Davey), Craig, J.E. (Jamie E.), Burdon, K.P. (Kathryn P.), Fogarty, R. (Rhys), Iyengar, S.K. (Sudha), Chew, E.Y. (Emily), Janmahasatian, S. (Sarayut), Martin, N.G. (Nicholas), MacGregor, S. (Stuart), Xu, L. (Liang), Schache, M. (Maria), Nangia, M. (Monika), Panda-Jonas, S. (Songhomitra), Wright, A.F. (Alan), Fondran, J.R. (Jeremy R.), Lass, J.H. (Jonathan H.), Feng, S. (Sheng), Zhao, J.H. (Jing Hua), Khaw, K.T., Wareham, N.J. (Nick), Rantanen, T. (Taina), Kaprio, J. (Jaakko), Pang, C.P. (Chi Pui), Chen, L.J. (Li Jia), Tam, P.O. (Pancy O.), Jhanji, V. (Vishal), Young, A.L. (Alvin L.), Döring, A. (Angela), Raffel, L.J. (Leslie), Cotch, M.-F. (Mary-Frances), Li, X. (Xiaohui), Yip, S.P. (Shea Ping), Yap, M.K.H. (Maurice K.H.), Biino, G. (Ginevra), Vaccargiu, S. (Simona), Fossarello, M. (Maurizio), Fleck, B. (Brian), Yazar, S. (Seyhan), Tideman, J.W.L. (Willem), Tedja, M. (Milly), Léveillard, T. (Thierry), Morrison, M.A. (Margaux A.), Farrer, L.A. (Lindsay), Zhou, X. (Xiangtian), Chen, W. (Wei), Mizuki, N. (Nobuhisa), Meguro, A. (Akira), Makela, K.M. (Kari Matti), Fan, Q. (Qiao), Verhoeven, V.J.M. (Virginie), Wojciechowski, R. (Robert), Barathi, V.A. (Veluchamy), Hysi, P.G. (Pirro), Guggenheim, J. (Jean), Höhn, R. (René), Vitart, V. (Veronique), Khawaja, A.P. (Anthony P.), Yamashiro, K. (Kenji), Hosseini, S.M. (S Mohsen), Lehtimäki, T. (Terho), Lu, Y. (Yi), Haller, T. (Toomas), Xie, J. (Jing), Delcourt, C. (Cécile), Pirastu, M. (Mario), Wedenoja, J. (Juho), Gharahkhani, P. (Puya), Venturini, C. (Cristina), Miyake, M. (Masahiro), Hewit, A.W. (Alex), Guo, X. (Xiaobo), Mazur, J. (Johanna), Huffman, J.E. (Jenifer E.), Williams, K.M. (Katie M.), Polasek, O. (Ozren), Campbell, H. (Harry), Rudan, I. (Igor), Vatavuk, Z. (Zoran), Wilson, J.F. (James F), Joshi, P.K. (Peter), Mcmahon, G. (George), St Pourcain, B. (Beate), Evans, D.M. (David), Simpson, C.L. (Claire), Schwantes-An, T.-H. (Tae-Hwi), Igo Jr., R.P. (Robert), Mirshahi, A. (Alireza), Cougnard-Grégoire, A. (Audrey), Bellenguez, C. (Céline), Blettner, M. (Maria), Raitakari, O. (Olli), Kähönen, M. (Mika), Seppälä, I. (Ilkka), Zeller, T. (Tanja), Meitinger, T. (Thomas), Ried, J.S. (Janina), Gieger, C. (Christian), Portas, L. (Laura), Leeuwen, E.M. (Elisa) van, Amin, N. (Najaf), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Vingerling, J.R. (Hans), Wang, Y. (Ying), Wang, X. (Xu), Tai-Hui Boh, E. (Eileen), Ikram, M.K. (Kamran), Sabanayagam, C. (Charumathi), Gupta, P. (Preeti), Tan, V. (Vincent), Zhou, L. (Lei), Ho, C.E.H. (Candice E. H.), Lim, W. (Wan'E), Beuerman, R.W. (Roger W.), Siantar, R. (Rosalynn), Tai, E.-S. (E-Shyong), Vithana, E.N. (Eranga), Mihailov, E. (Evelin), Khor, C.C., Hayward, C. (Caroline), Luben, R.N. (Robert), Foster, P.J. (Paul), Klein, B.E.K. (Barbara), Klein, R. (Ronald), Wong, H.-S. (Hoi-Suen), Mitchell, P. (Paul), Metspalu, A. (Andres), Aung, T. (Tin), Young, T.L. (Terri L.), He, M. (Mingguang), Pärssinen, O. (Olavi), Duijn, C.M. (Cornelia) van, Jin Wang, J. (Jie), Williams, C. (Cathy), Jonas, J.B. (Jost B.), Teo, Y.Y. (Yik Ying), Mackey, D.A. (David), Oexle, K. (Konrad), Yoshimura, N., Paterson, A.D. (Andrew D.), Pfeiffer, N. (Norbert), Wong, T.Y. (Tien Yin), Baird, P.N. (Paul), Stambolian, D. (Dwight), Wilson, J.E.B. (Joan E. Bailey), Cheng, C-Y. (Ching-Yu), Hammond, C.J. (Christopher J.), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Rahi, J.S. (Jugnoo), Korobelnik, J.-F. (Jean-François), Kemp, J.P. (John), Timpson, N.J. (Nicholas), Smith, A.V. (Davey), Craig, J.E. (Jamie E.), Burdon, K.P. (Kathryn P.), Fogarty, R. (Rhys), Iyengar, S.K. (Sudha), Chew, E.Y. (Emily), Janmahasatian, S. (Sarayut), Martin, N.G. (Nicholas), MacGregor, S. (Stuart), Xu, L. (Liang), Schache, M. (Maria), Nangia, M. (Monika), Panda-Jonas, S. (Songhomitra), Wright, A.F. (Alan), Fondran, J.R. (Jeremy R.), Lass, J.H. (Jonathan H.), Feng, S. (Sheng), Zhao, J.H. (Jing Hua), Khaw, K.T., Wareham, N.J. (Nick), Rantanen, T. (Taina), Kaprio, J. (Jaakko), Pang, C.P. (Chi Pui), Chen, L.J. (Li Jia), Tam, P.O. (Pancy O.), Jhanji, V. (Vishal), Young, A.L. (Alvin L.), Döring, A. (Angela), Raffel, L.J. (Leslie), Cotch, M.-F. (Mary-Frances), Li, X. (Xiaohui), Yip, S.P. (Shea Ping), Yap, M.K.H. (Maurice K.H.), Biino, G. (Ginevra), Vaccargiu, S. (Simona), Fossarello, M. (Maurizio), Fleck, B. (Brian), Yazar, S. (Seyhan), Tideman, J.W.L. (Willem), Tedja, M. (Milly), Léveillard, T. (Thierry), Morrison, M.A. (Margaux A.), Farrer, L.A. (Lindsay), Zhou, X. (Xiangtian), Chen, W. (Wei), Mizuki, N. (Nobuhisa), Meguro, A. (Akira), and Makela, K.M. (Kari Matti)

Abstract

Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10-5), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.

Published
2016
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4. Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium

Author

Fan, Q. (Qiao), Guo, X. (Xiaobo), Tideman, J.W.L. (Willem), Williams, K.M. (Katie M.), Yazar, S. (Seyhan), Hosseini, S.M. (S. Mohsen), Howe, L.D. (Laura), Pourcain, B.S. (Beate), Evans, D.M. (David), Timpson, N.J. (Nicholas), Mcmahon, G. (George), Hysi, P.G. (Pirro), Krapohl, E. (Eva), Wang, Y.X. (Ya Xing), Jonas, J.B., Baird, P.N. (Paul), Wang, J.J. (Jie Jin), Cheng, C.-Y. (Ching-Yu), Teo, Y.Y. (Yik Ying), Wong, T.-Y. (Tien-Yin), Ding, X. (Xiaohu), Wojciechowski, R. (Robert), Young, T.L. (Terri), Pärssinen, O. (Olavi), Oexle, K. (Konrad), Pfeiffer, A.F.H. (Andreas), Bailey-Wilson, J.E. (Joan E.), Paterson, A.D. (Andrew), Klaver, C.C.W. (Caroline C. W.), Plomin, R. (Robert), Hammond, C.J. (Christopher J.), He, M. (Mingguang), Saw, S-M. (Seang-Mei), Guggenheim, J. (Jean), Meguro, A. (Akira), Wright, A.F. (Alan), Hewit, A.W. (Alex), Young, A.L. (Alvin L.), Veluchamy, A.B. (Amutha Barathi), Metspalu, A. (Andres), Döring, A. (Angela), Khawaja, A.P. (Anthony P.), Klein, B.E.K. (Barbara), St Pourcain, B. (Beate), Fleck, B. (Brian), Klaver, C.C.W. (Caroline), Hayward, C. (Caroline), Williams, C. (Cathy), Delcourt, C. (Cécile), Pang, C.P. (Chi Pui), Khor, C.C., Gieger, C. (Christian), Simpson, C.L. (Claire), Duijn, C.M. (Cornelia) van, Mackey, D.A. (David), Stambolian, D. (Dwight), Chew, E.Y. (Emily), Tai, E.-S. (E.-Shyong), Mihailov, E. (Evelin), Smith, A.V. (Davey), Biino, G. (Ginevra), Campbell, H. (Harry), Rudan, I. (Igor), Seppälä, I. (Ilkka), Kaprio, J. (Jaakko), Wilson, J.F. (James F.), Craig, J.E. (Jamie E.), Ried, J.S. (Janina), Korobelnik, J.-F. (Jean-François), Fondran, J.R. (Jeremy R.), Liao, J. (Jie), Zhao, J.H. (Jing Hua), Xie, J. (Jing), Kemp, J.P. (John), Lass Jr., J.H. (Jonathan), Rahi, J.S. (Jugnoo), Wedenoja, J. (Juho), Makela, K.M. (Kari Matti), Burdon, K.P. (Kathryn P.), Khaw, K.T., Yamashiro, K. (Kenji), Chen, L.J. (Li Jia), Xu, L. (Liang), Farrer, L.A. (Lindsay), Ikram, M.K. (M. Kamran), DeAngelis, M.M. (Margaret), Morrison, M.A. (Margaux A.), Schache, M. (Maria), Pirastu, M. (Mario), Miyake, M. (Masahiro), Yap, M.K.H. (Maurice K. H.), Fossarello, M. (Maurizio), Kähönen, M. (Mika), Tedja, M. (Milly), Yoshimura, N., Martin, N.G. (Nicholas), Wareham, N.J. (Nick), Mizuki, N. (Nobuhisa), Raitakari, O. (Olli), Polasek, O. (Ozren), Tam, P.O. (Pancy O.), Foster, P.J. (Paul), Mitchell, P. (Paul), Chen, P. (Peng), Cumberland, P. (Phillippa), Gharahkhani, P. (Puya), Höhn, R. (René), Fogarty, R.D. (Rhys D.), Luben, R.N. (Robert), Igo Jr., R.P. (Robert), Klein, R. (Ronald), Janmahasatian, S. (Sarayut), Yip, S.P. (Shea Ping), Feng, S. (Sheng), Vaccargiu, S. (Simona), Panda-Jonas, S. (Songhomitra), MacGregor, S. (Stuart), Iyengar, S.K. (Sudha), Rantanen, T. (Taina), Lehtimäki, T. (Terho), Meitinger, T. (Thomas), Aung, T. (Tin), Haller, T. (Toomas), Vitart, V. (Veronique), Nangia, M. (Monika), Verhoeven, V.J.M. (Virginie), Jhanji, V. (Vishal), Zhao, W. (Wanting), Chen, W. (Wei), Zhou, X. (Xiangtian), Lu, Y. (Yi), Vatavuk, Z. (Zoran), Fan, Q. (Qiao), Guo, X. (Xiaobo), Tideman, J.W.L. (Willem), Williams, K.M. (Katie M.), Yazar, S. (Seyhan), Hosseini, S.M. (S. Mohsen), Howe, L.D. (Laura), Pourcain, B.S. (Beate), Evans, D.M. (David), Timpson, N.J. (Nicholas), Mcmahon, G. (George), Hysi, P.G. (Pirro), Krapohl, E. (Eva), Wang, Y.X. (Ya Xing), Jonas, J.B., Baird, P.N. (Paul), Wang, J.J. (Jie Jin), Cheng, C.-Y. (Ching-Yu), Teo, Y.Y. (Yik Ying), Wong, T.-Y. (Tien-Yin), Ding, X. (Xiaohu), Wojciechowski, R. (Robert), Young, T.L. (Terri), Pärssinen, O. (Olavi), Oexle, K. (Konrad), Pfeiffer, A.F.H. (Andreas), Bailey-Wilson, J.E. (Joan E.), Paterson, A.D. (Andrew), Klaver, C.C.W. (Caroline C. W.), Plomin, R. (Robert), Hammond, C.J. (Christopher J.), He, M. (Mingguang), Saw, S-M. (Seang-Mei), Guggenheim, J. (Jean), Meguro, A. (Akira), Wright, A.F. (Alan), Hewit, A.W. (Alex), Young, A.L. (Alvin L.), Veluchamy, A.B. (Amutha Barathi), Metspalu, A. (Andres), Döring, A. (Angela), Khawaja, A.P. (Anthony P.), Klein, B.E.K. (Barbara), St Pourcain, B. (Beate), Fleck, B. (Brian), Klaver, C.C.W. (Caroline), Hayward, C. (Caroline), Williams, C. (Cathy), Delcourt, C. (Cécile), Pang, C.P. (Chi Pui), Khor, C.C., Gieger, C. (Christian), Simpson, C.L. (Claire), Duijn, C.M. (Cornelia) van, Mackey, D.A. (David), Stambolian, D. (Dwight), Chew, E.Y. (Emily), Tai, E.-S. (E.-Shyong), Mihailov, E. (Evelin), Smith, A.V. (Davey), Biino, G. (Ginevra), Campbell, H. (Harry), Rudan, I. (Igor), Seppälä, I. (Ilkka), Kaprio, J. (Jaakko), Wilson, J.F. (James F.), Craig, J.E. (Jamie E.), Ried, J.S. (Janina), Korobelnik, J.-F. (Jean-François), Fondran, J.R. (Jeremy R.), Liao, J. (Jie), Zhao, J.H. (Jing Hua), Xie, J. (Jing), Kemp, J.P. (John), Lass Jr., J.H. (Jonathan), Rahi, J.S. (Jugnoo), Wedenoja, J. (Juho), Makela, K.M. (Kari Matti), Burdon, K.P. (Kathryn P.), Khaw, K.T., Yamashiro, K. (Kenji), Chen, L.J. (Li Jia), Xu, L. (Liang), Farrer, L.A. (Lindsay), Ikram, M.K. (M. Kamran), DeAngelis, M.M. (Margaret), Morrison, M.A. (Margaux A.), Schache, M. (Maria), Pirastu, M. (Mario), Miyake, M. (Masahiro), Yap, M.K.H. (Maurice K. H.), Fossarello, M. (Maurizio), Kähönen, M. (Mika), Tedja, M. (Milly), Yoshimura, N., Martin, N.G. (Nicholas), Wareham, N.J. (Nick), Mizuki, N. (Nobuhisa), Raitakari, O. (Olli), Polasek, O. (Ozren), Tam, P.O. (Pancy O.), Foster, P.J. (Paul), Mitchell, P. (Paul), Chen, P. (Peng), Cumberland, P. (Phillippa), Gharahkhani, P. (Puya), Höhn, R. (René), Fogarty, R.D. (Rhys D.), Luben, R.N. (Robert), Igo Jr., R.P. (Robert), Klein, R. (Ronald), Janmahasatian, S. (Sarayut), Yip, S.P. (Shea Ping), Feng, S. (Sheng), Vaccargiu, S. (Simona), Panda-Jonas, S. (Songhomitra), MacGregor, S. (Stuart), Iyengar, S.K. (Sudha), Rantanen, T. (Taina), Lehtimäki, T. (Terho), Meitinger, T. (Thomas), Aung, T. (Tin), Haller, T. (Toomas), Vitart, V. (Veronique), Nangia, M. (Monika), Verhoeven, V.J.M. (Virginie), Jhanji, V. (Vishal), Zhao, W. (Wanting), Chen, W. (Wei), Zhou, X. (Xiangtian), Lu, Y. (Yi), and Vatavuk, Z. (Zoran)

Abstract

Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).

Published
2016
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5. Prevalence of refractive error in Europe: the European Eye Epidemiology (E3) Consortium

Author

Williams, K.M. (Katie M.), Verhoeven, V.J.M. (Virginie), Cumberland, P. (Phillippa), Bertelsen, G. (Geir), Wolfram, C. (Christian), Buitendijk, G.H.S. (Gabrielle), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Vingerling, J.R. (Hans), Kuijpers, R.W.A.M. (Robert), Höhn, R. (René), Mirshahi, A. (Alireza), Khawaja, A.P. (Anthony P.), Luben, R.N. (Robert N.), Erke, M.G. (Maja Gran), Von Hanno, T. (Therese), Mahroo, O. (Omar), Hogg, R. (Ruth), Gieger, C. (Christian), Cougnard-Grégoire, A. (Audrey), Anastasopoulos, E. (Eleftherios), Bron, A. (Alain), Dartigues, J.-F., Korobelnik, J.-F. (Jean-François), Creuzot-Garcher, C. (Catherine), Topouzis, F. (Fotis), Delcourt, C. (Cécile), Rahi, J.S. (Jugnoo), Meitinger, T. (Thomas), Fletcher, A. (Astrid), Foster, P.J. (Paul J.), Pfeiffer, N. (Norbert), Klaver, C.C.W. (Caroline), Hammond, C.J. (Christopher), Williams, K.M. (Katie M.), Verhoeven, V.J.M. (Virginie), Cumberland, P. (Phillippa), Bertelsen, G. (Geir), Wolfram, C. (Christian), Buitendijk, G.H.S. (Gabrielle), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Vingerling, J.R. (Hans), Kuijpers, R.W.A.M. (Robert), Höhn, R. (René), Mirshahi, A. (Alireza), Khawaja, A.P. (Anthony P.), Luben, R.N. (Robert N.), Erke, M.G. (Maja Gran), Von Hanno, T. (Therese), Mahroo, O. (Omar), Hogg, R. (Ruth), Gieger, C. (Christian), Cougnard-Grégoire, A. (Audrey), Anastasopoulos, E. (Eleftherios), Bron, A. (Alain), Dartigues, J.-F., Korobelnik, J.-F. (Jean-François), Creuzot-Garcher, C. (Catherine), Topouzis, F. (Fotis), Delcourt, C. (Cécile), Rahi, J.S. (Jugnoo), Meitinger, T. (Thomas), Fletcher, A. (Astrid), Foster, P.J. (Paul J.), Pfeiffer, N. (Norbert), Klaver, C.C.W. (Caroline), and Hammond, C.J. (Christopher)

Abstract

To estimate the prevalence of refractive error in adults across Europe. Refractive data (mean spherical equivalent) collected between 1990 and 2013 from fifteen population-based cohort and cross-sectional studies of the European Eye Epidemiology (E3) Consortium were combined in a random effects meta-analysis stratified by 5-year age intervals and gender. Participants were excluded if they were identified as having had cataract surgery, retinal detachment, refractive surgery or other factors that might influence refraction. Estimates of refractive error prevalence were obtained including the following classifications: myopia ≤−0.75 diopters (D), high myopia ≤−6D, hyperopia ≥1D and astigmatism ≥1D. Meta-analysis of refractive error was performed for 61,946 individuals from fifteen studies with median age ranging from 44 to 81 and minimal ethnic variation (98 % European ancestry). The age-standardised prevalences (using the 2010 European Standard Population, limited to those ≥25 and <90 years old) were: myopia 30.6 % [95 % confidence interval (CI) 30.4–30.9], high myopia 2.7 % (95 % CI 2.69–2.73), hyperopia 25.2 % (95 % CI 25.0–25.4) and astigmatism 23.9 % (95 % CI 23.7–24.1). Age-specific estimates revealed a high prevalence of myopia in younger participants [47.2 % (CI 41.8–52.5) in 25–29 years-olds]. Refractive error affects just over a half of European adults. The greatest burden of refractive error is due to myopia, with high prevalence rates in young adults. Using the 2010 European population estimates, we estimate there are 227.2 million people with myopia across Europe.

Published
2015
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6. Increasing Prevalence of Myopia in Europe and the Impact of Education

Author

Williams, K.M. (Katie M.), Bertelsen, G. (Geir), Cumberland, P. (Phillippa), Wolfram, C. (Christian), Verhoeven, V.J.M. (Virginie), Anastasopoulos, E. (Eleftherios), Buitendijk, G.H.S. (Gabrielle), Cougnard-Grégoire, A. (Audrey), Creuzot-Garcher, C. (Catherine), Erke, M.G. (Maja Gran), Hogg, R. (Ruth), Höhn, R. (René), Hysi, P.G. (Pirro), Khawaja, A.P. (Anthony P.), Korobelnik, J.-F. (Jean-François), Ried, J.S. (Janina), Vingerling, J.R. (Hans), Bron, A. (Alain), Dartigues, J.-F. (Jean-François), Fletcher, A. (Astrid), Hofman, A. (Albert), Kuijpers, R.W.A.M. (Robert), Luben, R.N. (Robert N.), Oxele, K. (Konrad), Topouzis, F. (Fotis), Von Hanno, T. (Therese), Mirshahi, A. (Alireza), Foster, P.J. (Paul J.), Duijn, C.M. (Cornelia) van, Pfeiffer, A.F.H. (Andreas), Delcourt, C. (Cécile), Klaver, C.C.W. (Caroline), Rahi, J.S. (Jugnoo), Hammond, C.J. (Christopher), Williams, K.M. (Katie M.), Bertelsen, G. (Geir), Cumberland, P. (Phillippa), Wolfram, C. (Christian), Verhoeven, V.J.M. (Virginie), Anastasopoulos, E. (Eleftherios), Buitendijk, G.H.S. (Gabrielle), Cougnard-Grégoire, A. (Audrey), Creuzot-Garcher, C. (Catherine), Erke, M.G. (Maja Gran), Hogg, R. (Ruth), Höhn, R. (René), Hysi, P.G. (Pirro), Khawaja, A.P. (Anthony P.), Korobelnik, J.-F. (Jean-François), Ried, J.S. (Janina), Vingerling, J.R. (Hans), Bron, A. (Alain), Dartigues, J.-F. (Jean-François), Fletcher, A. (Astrid), Hofman, A. (Albert), Kuijpers, R.W.A.M. (Robert), Luben, R.N. (Robert N.), Oxele, K. (Konrad), Topouzis, F. (Fotis), Von Hanno, T. (Therese), Mirshahi, A. (Alireza), Foster, P.J. (Paul J.), Duijn, C.M. (Cornelia) van, Pfeiffer, A.F.H. (Andreas), Delcourt, C. (Cécile), Klaver, C.C.W. (Caroline), Rahi, J.S. (Jugnoo), and Hammond, C.J. (Christopher)

Abstract

Purpose To investigate whether myopia is becoming more common across Europe and explore whether increasing education levels, an important environmental risk factor for myopia, might explain any temporal trend. Design Meta-analysis of population-based, cross-sectional studies from the European Eye Epidemiology (E3) Consortium. Participants The E3 Consortium is a collaborative network of epidemiological studies of common eye diseases in adults across Europe. Refractive data were available for 61 946 participants from 15 population-based studies performed between 1990 and 2013; participants had a range of median ages from 44 to 78 years. Methods Noncycloplegic refraction, year of birth, and highest educational level achieved were obtained for all participants. Myopia was defined as a mean spherical equivalent ≤-0.75 diopters. A random-effects meta-analysis of age-specific myopia prevalence was performed, with sequential analyses stratified by year of birth and highest level of educational attainment. Main Outcome Measures Variation in age-specific myopia prevalence for differing years of birth and educational level. Results There was a significant cohort effect for increasing myopia prevalence across more recent birth decades; age-standardized myopia prevalence increased from 17.8% (95% confidence interval [CI], 17.6-18.1) to 23.5% (95% CI, 23.2-23.7) in those born between 1910 and 1939 compared with 1940 and 1979 (P = 0.03). Education was significantly associated with myopia; for those completing primary, secondary, and higher education, the age-standardized prevalences were 25.4% (CI, 25.0-25.8), 29.1% (CI, 28.8-29.5), and 36.6% (CI, 36.1-37.2), respectively. Although more recent birth cohorts were more educated, this did not fully explain the cohort effect. Compared with the reference risk of participants born in the 1920s with only primary education, higher education or being born in the 1960s doubled the myopia prevalence ratio-2.43 (CI, 1.26

Published
2015
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