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Your search keyword '"Springelkamp, H. (Henriët)"' showing total 14 results
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14 results on '"Springelkamp, H. (Henriët)"'

1. Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

Author

Bonnemaijer, P.W.M. (Pieter), Leeuwen, E.M. (Elisabeth M. van), Iglesias, A.I. (Adriana I.), Gharahkhani, P. (Puya), Vitart, V. (Veronique), Khawaja, A.P. (Anthony), Simcoe, M. (Mark), Höhn, R. (René), Cree, A.J. (Angela), Igo Jr., R.P. (Robert), Burdon, K.P. (Kathryn P.), Craig, J.E. (Jamie), Hewit, A.W. (Alex), Jonas, J.B., Khor, C.-C. (Chiea-Cheun), Pasutto, F. (Francesca), Mackey, D.A. (David), Mitchell, P. (Paul), Mishra, A. (Aniket), Pang, C.P. (Chi Pui), Pasquale, L.R. (Louis R), Springelkamp, H. (Henriët), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Viswanathan, A.C. (Ananth C.), Wojciechowski, R. (Robert), Wong, T.Y. (Tien Yin), Young, T.L. (Terrri L), Zeller, T. (Tanja), Allingham, R.R. (R Rand), Budenz, D.L. (Donald L.), Bailey, J.C. (Jessica Cooke), Fingert, J. (John), Gaasterland, D. (Douglas), Gaasterland, T. (Terry), Haines, J.L. (Jonathan), Hark, L. (Lisa), Hauser, M.A. (Michael), Kang, J.H. (Jae Hee), Kraft, P. (Peter), Lee, R.K. (Richard K.), Lichter, P.A. (Paul A.), Liu, Y. (Yutao), Moroi, S. (Syoko), Pasquale, L.R. (Louis), Pericak, M. (Margaret), Realini, A. (Anthony), Rhee, D. (Doug), Richards, J.R. (Julia R.), Ritch, R. (Robert), Scott, W.K. (William), Singh, K. (Kuldev), Sit, A.J. (Arthur J.), Vollrath, D. (Douglas), Weinreb, R.N. (Robert N.), Wollstein, G. (Gadi), Wilmer, D.Z. (Don Zack), Atan, D. (Denize), Aslam, T. (Tariq), Barman, S.A. (Sarah A.), Barrett, J.H. (Jennifer H.), Bishop, P.N. (Paul), Blows, P. (Peter), Bunce, C. (Catey), Carare, R.O. (Roxana O.), Chakravarthy, U. (Usha), Chan, M. (Michelle), Chua, S.Y.L. (Sharon Y. L.), Crabb, D.P. (David), Cumberland, P.M. (Philippa M.), Day, A. (Alexander), Desai, P. (Parul), Dhillon, B. (Bal), Dick, A.D. (Andrew D.), Egan, C. (Cathy), Ennis, S. (Sarah), Foster, P.J. (Paul), Fruttiger, M. (Marcus), Gallacher, J.E.J. (John E. J.), Garway, D.F. (David F.), Gibson, J. (Jane), Dan Gore, (), Guggenheim, J. (Jean), Hardcastle, A. (Alison), Harding, S.P. (Simon), Hogg, R. (Ruth), Keane, P.A. (Pearse A.), Khaw, P.T. (Peng T.), Lascaratos, G. (Gerassimos), Macgillivray, T. (Tom), Mackie, S. (Sarah), Martin, K. (Keith), McGaughey, M. (Michelle), McGuinness, B. (Bernadette), McKay, G.J. (Gareth), McKibbin, M. (Martin), Mitry, D. (Danny), Moore, T. (Tony), Morgan, J.E. (James E.), Muthy, Z.A. (Zaynah A.), O’Sullivan, E. (Eoin), Owen, C.G. (Chris G.), Patel, P. (Praveen), Paterson, E. (Euan), Peto, T. (Tünde), Petzold, A. (Axel), Rahi, J.S. (Jugnoo S.), Rudnikca, A.R. (Alicja R.), Self, J. (Jay), Sivaprasad, S., Steel, D. (David), Stratton, I. (Irene), Strouthidis, N. (Nicholas), Sudlow, C. (Cathie), Thomas, D. (Dhanes), Trucco, E. (Emanuele), Tufail, A. (Adnan), Vernon, S.A. (Stephen A.), Williams, C. (Cathy), Williams, K.M. (Katie M.), Woodside, J.V. (J.), Yates, M.M. (Max M.), Yip, J. (Jennifer), Zheng, Y. (Yalin), Gerhold-Ay, A. (Aslihan), Nickels, S. (Stefan), Wilson, J.F. (James), Hayward, C. (Caroline), Boutin, T.S. (Thibaud S.), Polasek, O. (Ozren), Aung, T. (Tin), Khor, C.C., Amin, N. (Najaf), Lotery, A.J. (Andrew), Wiggs, J.L. (Janey L.), Cheng, C.-Y. (Ching-Yu), Hysi, P.G. (Pirro G.), Hammond, C.J. (Christopher), Thiadens, A.A.H.J. (Alberta), MacGregor, S. (Stuart), Klaver, C.C.W. (Caroline), Duijn, C.M. (Cornelia) van, Bonnemaijer, P.W.M. (Pieter), Leeuwen, E.M. (Elisabeth M. van), Iglesias, A.I. (Adriana I.), Gharahkhani, P. (Puya), Vitart, V. (Veronique), Khawaja, A.P. (Anthony), Simcoe, M. (Mark), Höhn, R. (René), Cree, A.J. (Angela), Igo Jr., R.P. (Robert), Burdon, K.P. (Kathryn P.), Craig, J.E. (Jamie), Hewit, A.W. (Alex), Jonas, J.B., Khor, C.-C. (Chiea-Cheun), Pasutto, F. (Francesca), Mackey, D.A. (David), Mitchell, P. (Paul), Mishra, A. (Aniket), Pang, C.P. (Chi Pui), Pasquale, L.R. (Louis R), Springelkamp, H. (Henriët), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Viswanathan, A.C. (Ananth C.), Wojciechowski, R. (Robert), Wong, T.Y. (Tien Yin), Young, T.L. (Terrri L), Zeller, T. (Tanja), Allingham, R.R. (R Rand), Budenz, D.L. (Donald L.), Bailey, J.C. (Jessica Cooke), Fingert, J. (John), Gaasterland, D. (Douglas), Gaasterland, T. (Terry), Haines, J.L. (Jonathan), Hark, L. (Lisa), Hauser, M.A. (Michael), Kang, J.H. (Jae Hee), Kraft, P. (Peter), Lee, R.K. (Richard K.), Lichter, P.A. (Paul A.), Liu, Y. (Yutao), Moroi, S. (Syoko), Pasquale, L.R. (Louis), Pericak, M. (Margaret), Realini, A. (Anthony), Rhee, D. (Doug), Richards, J.R. (Julia R.), Ritch, R. (Robert), Scott, W.K. (William), Singh, K. (Kuldev), Sit, A.J. (Arthur J.), Vollrath, D. (Douglas), Weinreb, R.N. (Robert N.), Wollstein, G. (Gadi), Wilmer, D.Z. (Don Zack), Atan, D. (Denize), Aslam, T. (Tariq), Barman, S.A. (Sarah A.), Barrett, J.H. (Jennifer H.), Bishop, P.N. (Paul), Blows, P. (Peter), Bunce, C. (Catey), Carare, R.O. (Roxana O.), Chakravarthy, U. (Usha), Chan, M. (Michelle), Chua, S.Y.L. (Sharon Y. L.), Crabb, D.P. (David), Cumberland, P.M. (Philippa M.), Day, A. (Alexander), Desai, P. (Parul), Dhillon, B. (Bal), Dick, A.D. (Andrew D.), Egan, C. (Cathy), Ennis, S. (Sarah), Foster, P.J. (Paul), Fruttiger, M. (Marcus), Gallacher, J.E.J. (John E. J.), Garway, D.F. (David F.), Gibson, J. (Jane), Dan Gore, (), Guggenheim, J. (Jean), Hardcastle, A. (Alison), Harding, S.P. (Simon), Hogg, R. (Ruth), Keane, P.A. (Pearse A.), Khaw, P.T. (Peng T.), Lascaratos, G. (Gerassimos), Macgillivray, T. (Tom), Mackie, S. (Sarah), Martin, K. (Keith), McGaughey, M. (Michelle), McGuinness, B. (Bernadette), McKay, G.J. (Gareth), McKibbin, M. (Martin), Mitry, D. (Danny), Moore, T. (Tony), Morgan, J.E. (James E.), Muthy, Z.A. (Zaynah A.), O’Sullivan, E. (Eoin), Owen, C.G. (Chris G.), Patel, P. (Praveen), Paterson, E. (Euan), Peto, T. (Tünde), Petzold, A. (Axel), Rahi, J.S. (Jugnoo S.), Rudnikca, A.R. (Alicja R.), Self, J. (Jay), Sivaprasad, S., Steel, D. (David), Stratton, I. (Irene), Strouthidis, N. (Nicholas), Sudlow, C. (Cathie), Thomas, D. (Dhanes), Trucco, E. (Emanuele), Tufail, A. (Adnan), Vernon, S.A. (Stephen A.), Williams, C. (Cathy), Williams, K.M. (Katie M.), Woodside, J.V. (J.), Yates, M.M. (Max M.), Yip, J. (Jennifer), Zheng, Y. (Yalin), Gerhold-Ay, A. (Aslihan), Nickels, S. (Stefan), Wilson, J.F. (James), Hayward, C. (Caroline), Boutin, T.S. (Thibaud S.), Polasek, O. (Ozren), Aung, T. (Tin), Khor, C.C., Amin, N. (Najaf), Lotery, A.J. (Andrew), Wiggs, J.L. (Janey L.), Cheng, C.-Y. (Ching-Yu), Hysi, P.G. (Pirro G.), Hammond, C.J. (Christopher), Thiadens, A.A.H.J. (Alberta), MacGregor, S. (Stuart), Klaver, C.C.W. (Caroline), and Duijn, C.M. (Cornelia) van

Abstract

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.

Published
2019
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2. Genomic locus modulating corneal thickness in the mouse identifies POU6F2 as a potential risk of developing glaucoma

Author

King, R. (Richard), Struebing, F.L., Li, Y. (Yuwen), Wang, J., Koch, A.A., Bailey, JNC, Gharahkhani, P, Macgregor, S., Allingham, R.R. (R Rand), Hauser, M.A. (Michael), Wiggs, J.L. (Janey), Geisert, E.E., Allingham, R., Brilliant, M., Budenz, D., Bailey, J.C., Fingert, J., Gaasterland, D., Gaasterland, T., Haines, J.L. (Jonathan), Hark, L., Hauser, M., Igo, R., Kang, J.H. (Jae), Kraft, P. (Peter), Lee, R. (R.) van der, Lichter, P. (Peter), Liu, Y. (Yu), Moroi, S., Pasquale, L.R. (Louis), Pericak-Vance, M.A. (Margaret), Realini, A., Rhee, D., Richards, J. (John), Ritch, R., Schuman, J., Scott, W.K. (William), Singh, K, Sit, A., Vollrath, D., Weinreb, RN, Wollstein, G., Zack, D., Aung, T. (Tin), Burdon, K.P. (Kathryn), Cheng, C-Y. (Ching-Yu), Bailey, J.N.C., Craig, J.E. (Jamie), Cree, A.J. (Angela), Hammond, C.J. (Christopher), Hewit, A.W. (Alex), Höhn, R., Hysi, P.G. (Pirro), Gonzalez, A.I., Jonas, J., Khawaja, A, Khor, C.C., Klaver, C.C.W. (Caroline), Pasutto, F. (Francesca), Mackey, D., Mitchell, P. (Paul), Mishra, A. (Aniket), Pang, C., Springelkamp, H. (Henriët), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Duijn, C.M., Viswanathan, A. (Anand), Vitart, V. (Veronique), Wojciechowski, R. (Robert), Wong, T., Young, T.L. (Terri), Zeller, T. (Tanja), King, R. (Richard), Struebing, F.L., Li, Y. (Yuwen), Wang, J., Koch, A.A., Bailey, JNC, Gharahkhani, P, Macgregor, S., Allingham, R.R. (R Rand), Hauser, M.A. (Michael), Wiggs, J.L. (Janey), Geisert, E.E., Allingham, R., Brilliant, M., Budenz, D., Bailey, J.C., Fingert, J., Gaasterland, D., Gaasterland, T., Haines, J.L. (Jonathan), Hark, L., Hauser, M., Igo, R., Kang, J.H. (Jae), Kraft, P. (Peter), Lee, R. (R.) van der, Lichter, P. (Peter), Liu, Y. (Yu), Moroi, S., Pasquale, L.R. (Louis), Pericak-Vance, M.A. (Margaret), Realini, A., Rhee, D., Richards, J. (John), Ritch, R., Schuman, J., Scott, W.K. (William), Singh, K, Sit, A., Vollrath, D., Weinreb, RN, Wollstein, G., Zack, D., Aung, T. (Tin), Burdon, K.P. (Kathryn), Cheng, C-Y. (Ching-Yu), Bailey, J.N.C., Craig, J.E. (Jamie), Cree, A.J. (Angela), Hammond, C.J. (Christopher), Hewit, A.W. (Alex), Höhn, R., Hysi, P.G. (Pirro), Gonzalez, A.I., Jonas, J., Khawaja, A, Khor, C.C., Klaver, C.C.W. (Caroline), Pasutto, F. (Francesca), Mackey, D., Mitchell, P. (Paul), Mishra, A. (Aniket), Pang, C., Springelkamp, H. (Henriët), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Duijn, C.M., Viswanathan, A. (Anand), Vitart, V. (Veronique), Wojciechowski, R. (Robert), Wong, T., Young, T.L. (Terri), and Zeller, T. (Tanja)

Abstract

Central corneal thickness (CCT) is one of the most heritable ocular traits and it is also a phenotypic risk factor for primary open angle glaucoma (POAG). The present study uses the BXD Recombinant Inbred (RI) strains to identify novel quantitative trait loci (QTLs) modulating CCT in the mouse with the potential of identifying a molecular link between CCT and risk of developing POAG. The BXD RI strain set was used to define mammalian genomic loci modulating CCT, with a total of 818 corneas measured from 61 BXD RI strains (between 60–100 days of age). The mice were anesthetized and the eyes were positioned in front of the lens of the Phoenix Micron IV Image-Guided OCT system or the Bioptigen OCT system. CCT data for each strain was averaged and used to QTLs modulating this phenotype using the bioinformatics tools on GeneNetwork (www.genenetwork.org). The candidate genes and genomic loci identified in the mouse were then directly compared with the summary data from a human POAG genome wide association study (NEIGHBORHOOD) to determine if any genomic elements modulating mouse CCT are also risk factors for POAG.This analysis revealed one significant QTL on Chr 13 and a suggestive QTL on Chr 7. The significant locus on Chr 13 (13 to 19 Mb) was examined further to define candidate genes modulating this eye phenotype. For the Chr 13 QTL in the mouse, only one gene in the region (Pou6f2) contained nonsynonymous SNPs. Of these five nonsynonymous SNPs in Pou6f2, two resulted in changes in the amino acid proline which could result in altered secondary structure affecting protein function. The 7 Mb region under the mouse Chr 13 peak distributes over 2 chromosomes in the human: Chr 1 and Chr 7. These genomic loci were examined in the NEIGHBORHOOD database to determine if they are potential risk factors for human glaucoma identified using meta-data from human GWAS. The top 50 hits all resided within one gene (POU6F2), with the highest significance level of p = 10−6 for SNP rs7631

Published
2018
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3. Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Author

Iglesias, A.I. (Adriana I.), Mishra, A. (Aniket), Vitart, V. (Veronique), Bykhovskaya, Y. (Yelena), Höhn, R. (René), Springelkamp, H. (Henriët), Cuellar-Partida, G. (Gabriel), Gharahkhani, P. (Puya), Bailey, J.N.C. (Jessica N. Cooke), Willoughby, C.E. (Colin E.), Li, X. (Xiaohui), Yazar, S. (Seyhan), Nag, A. (Abhishek), Khawaja, A.P. (Anthony), Polasek, O. (Ozren), Siscovick, D.S. (David), Mitchell, P. (Paul), Tham, Y.C. (Yih Chung), Haines, J.L. (Jonathan), Kearns, L.S. (Lisa S.), Hayward, C. (Caroline), Shi, Y. (Yuan), Van Leeuwen, E.M. (Elisabeth M.), Taylor, K.D. (Kent), Wang, J.J. (Jie Jin), Rochtchina, E. (Elena), Attia, J. (John), Scott, R. (Rodney), Holliday, E.G. (Elizabeth), Baird, P.N. (Paul), Xie, J. (Jing), Inouye, M. (Michael), Viswanathan, A. (Ananth), Sim, X. (Xueling), Bonnemaijer, P.W.M. (Pieter), Rotter, J.I. (Jerome I.), Martin, N.G. (Nicholas G.), Zeller, T. (Tanja), Mills, R.A. (Richard), Staffieri, S.E. (Sandra E.), Jonas, J.B. (Jost B.), Schmidtmann, I. (Irene), Boutin, T. (Thibaud), Kang, J.H. (Jae H.), Lucas, S.E.M. (Sionne E.M.), Wong, T.Y. (Tien Yin), Beutel, M.E. (Manfred E.), Wilson, J.F. (James F.), Allingham, R.R. (R Rand), Brilliant, M.H. (Murray H.), Budenz, D.L. (Donald L.), Christen, W.G. (William G.), Fingert, J. (John), Friedman, D.S. (David), Gaasterland, D. (Douglas), Gaasterland, T. (Terry), Hauser, M.A. (Michael), Kraft, P. (Peter), Lee, R.K. (Richard K.), Lichter, P.A. (Paul A.), Liu, Y. (Yutao), Loomis, S.J. (Stephanie J.), Moroi, S.E. (Sayoko), Pericak-Vance, M.A. (Margaret), Realini, A. (Anthony), Richards, J.E. (Julia E.), Schuman, J.S. (Joel S.), Scott, W.K. (William), Singh, K. (Kuldev), Sit, A.J. (Arthur J.), Vollrath, D. (Douglas), Weinreb, R.N. (Robert N.), Wollstein, G. (Gadi), Zack, D.J. (Donald), Zhang, K. (Kang), Donnelly, P. (Peter), Barroso, I.E. (Inês), Blackwell, J.M. (Jenefer M.), Bramon, E. (Elvira), Brown, M.A. (Matthew), Casas, J.P. (Juan), Corvin, A. (Aiden), Deloukas, P. (Panos), Duncanson, A. (Audrey), Jankowski, J. (Janusz), Markus, H.S. (Hugh), Mathew, J. (Joseph), Palmer, C.N.A. (Colin), Plomin, R. (Robert), Rautanen, A. (Anna), Sawcer, S.J. (Stephen), Trembath, R.C. (Richard), Wood, N.W. (Nicholas W.), Spencer, C.C.A. (Chris C.), Band, G. (Gavin), Bellenguez, C. (Céline), Freeman, C. (Colin), Hellenthal, F.A., Giannoulatou, E. (Eleni), Pirinen, M. (Matti), Pearson, R. (Ruth), Strange, A. (Amy), Su, Z. (Zhan), Vukcevic, D. (Damjan), Langford, C. (Cordelia), Hunt, S.E. (Sarah E.), Edkins, T. (Ted), Gwilliam, R. (Rhian), Blackburn, H. (Hannah), Bumpstead, S. (Suzannah), Dronov, S. (Serge), Gillman, M. (Matthew), Gray, E. (Emma), Hammond, N. (Naomi), Jayakumar, A. (Alagurevathi), McCann, O.T. (Owen), Liddle, J. (Jennifer), Potter, S.C. (Simon), Ravindrarajah, R. (Radhi), Ricketts, M. (Michelle), Waller, P. (Patrick), Weston, P. (Paul), Widaa, S. (Sara), Whittaker, P. (Pamela), Uitterlinden, A.G. (André), Vithana, E.N. (Eranga), Foster, P.J. (Paul), Hysi, P.G. (Pirro), Hewitt, A.W. (Alex W.), Khor, C.C., Pasquale, L.R. (Louis), Montgomery, G.W. (Grant W.), Klaver, C.C.W. (Caroline), Aung, T. (Tin), Pfeiffer, A.F.H. (Andreas), Mackey, D.A. (David), Hammond, C.J. (Christopher), Cheng, C.-Y. (Ching-Yu), Craig, J.E. (Jamie), Rabinowitz, Y.S. (Yaron), Wiggs, J.L. (Janey L.), Burdon, K.P. (Kathryn), Duijn, C.M. (Cornelia) van, MacGregor, S. (Stuart), Iglesias, A.I. (Adriana I.), Mishra, A. (Aniket), Vitart, V. (Veronique), Bykhovskaya, Y. (Yelena), Höhn, R. (René), Springelkamp, H. (Henriët), Cuellar-Partida, G. (Gabriel), Gharahkhani, P. (Puya), Bailey, J.N.C. (Jessica N. Cooke), Willoughby, C.E. (Colin E.), Li, X. (Xiaohui), Yazar, S. (Seyhan), Nag, A. (Abhishek), Khawaja, A.P. (Anthony), Polasek, O. (Ozren), Siscovick, D.S. (David), Mitchell, P. (Paul), Tham, Y.C. (Yih Chung), Haines, J.L. (Jonathan), Kearns, L.S. (Lisa S.), Hayward, C. (Caroline), Shi, Y. (Yuan), Van Leeuwen, E.M. (Elisabeth M.), Taylor, K.D. (Kent), Wang, J.J. (Jie Jin), Rochtchina, E. (Elena), Attia, J. (John), Scott, R. (Rodney), Holliday, E.G. (Elizabeth), Baird, P.N. (Paul), Xie, J. (Jing), Inouye, M. (Michael), Viswanathan, A. (Ananth), Sim, X. (Xueling), Bonnemaijer, P.W.M. (Pieter), Rotter, J.I. (Jerome I.), Martin, N.G. (Nicholas G.), Zeller, T. (Tanja), Mills, R.A. (Richard), Staffieri, S.E. (Sandra E.), Jonas, J.B. (Jost B.), Schmidtmann, I. (Irene), Boutin, T. (Thibaud), Kang, J.H. (Jae H.), Lucas, S.E.M. (Sionne E.M.), Wong, T.Y. (Tien Yin), Beutel, M.E. (Manfred E.), Wilson, J.F. (James F.), Allingham, R.R. (R Rand), Brilliant, M.H. (Murray H.), Budenz, D.L. (Donald L.), Christen, W.G. (William G.), Fingert, J. (John), Friedman, D.S. (David), Gaasterland, D. (Douglas), Gaasterland, T. (Terry), Hauser, M.A. (Michael), Kraft, P. (Peter), Lee, R.K. (Richard K.), Lichter, P.A. (Paul A.), Liu, Y. (Yutao), Loomis, S.J. (Stephanie J.), Moroi, S.E. (Sayoko), Pericak-Vance, M.A. (Margaret), Realini, A. (Anthony), Richards, J.E. (Julia E.), Schuman, J.S. (Joel S.), Scott, W.K. (William), Singh, K. (Kuldev), Sit, A.J. (Arthur J.), Vollrath, D. (Douglas), Weinreb, R.N. (Robert N.), Wollstein, G. (Gadi), Zack, D.J. (Donald), Zhang, K. (Kang), Donnelly, P. (Peter), Barroso, I.E. (Inês), Blackwell, J.M. (Jenefer M.), Bramon, E. (Elvira), Brown, M.A. (Matthew), Casas, J.P. (Juan), Corvin, A. (Aiden), Deloukas, P. (Panos), Duncanson, A. (Audrey), Jankowski, J. (Janusz), Markus, H.S. (Hugh), Mathew, J. (Joseph), Palmer, C.N.A. (Colin), Plomin, R. (Robert), Rautanen, A. (Anna), Sawcer, S.J. (Stephen), Trembath, R.C. (Richard), Wood, N.W. (Nicholas W.), Spencer, C.C.A. (Chris C.), Band, G. (Gavin), Bellenguez, C. (Céline), Freeman, C. (Colin), Hellenthal, F.A., Giannoulatou, E. (Eleni), Pirinen, M. (Matti), Pearson, R. (Ruth), Strange, A. (Amy), Su, Z. (Zhan), Vukcevic, D. (Damjan), Langford, C. (Cordelia), Hunt, S.E. (Sarah E.), Edkins, T. (Ted), Gwilliam, R. (Rhian), Blackburn, H. (Hannah), Bumpstead, S. (Suzannah), Dronov, S. (Serge), Gillman, M. (Matthew), Gray, E. (Emma), Hammond, N. (Naomi), Jayakumar, A. (Alagurevathi), McCann, O.T. (Owen), Liddle, J. (Jennifer), Potter, S.C. (Simon), Ravindrarajah, R. (Radhi), Ricketts, M. (Michelle), Waller, P. (Patrick), Weston, P. (Paul), Widaa, S. (Sara), Whittaker, P. (Pamela), Uitterlinden, A.G. (André), Vithana, E.N. (Eranga), Foster, P.J. (Paul), Hysi, P.G. (Pirro), Hewitt, A.W. (Alex W.), Khor, C.C., Pasquale, L.R. (Louis), Montgomery, G.W. (Grant W.), Klaver, C.C.W. (Caroline), Aung, T. (Tin), Pfeiffer, A.F.H. (Andreas), Mackey, D.A. (David), Hammond, C.J. (Christopher), Cheng, C.-Y. (Ching-Yu), Craig, J.E. (Jamie), Rabinowitz, Y.S. (Yaron), Wiggs, J.L. (Janey L.), Burdon, K.P. (Kathryn), Duijn, C.M. (Cornelia) van, and MacGregor, S. (Stuart)

Abstract

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r =-0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r =-0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.

Published
2018
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4. 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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5. New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics.

Author

Springelkamp, H. (Henriët), Iglesias, A.I. (Adriana), Mishra, A. (Aniket), Höhn, R. (René), Wojciechowski, R. (Robert), Khawaja, A.P. (Anthony), Nag, A. (Abhishek), Wang, Y.X. (Ya Xing), Wang, J.J. (Jie Jin), Cuellar-Partida, G. (Gabriel), Gibson, J. (Jane), Cooke Bailey, J.N. (Jessica), Vithana, E.N. (Eranga), Gharahkhani, P. (Puya), Boutin, T. (Thibaud), Ramdas, W.D. (Wishal), Zeller, T. (Tanja), Luben, R.N. (Robert), Yonova-Doing, E. (Ekaterina), Viswanathan, A.C. (Ananth), Yazar, S. (Seyhan), Cree, A.J. (Angela), Haines, J.L. (Jonathan), Koh, J.Y. (Jia Yu), Souzeau, E. (Emmanuelle), Wilson, J.F. (James), Amin, N. (Najaf), Müller, C. (Christian), Venturini, C. (Cristina), Kearns, L.S. (Lisa), Hee Kang, J. (Jae), Consortium, N. (Neighborhood), Tham, Y.C. (Yih Chung), Zhou, T. (Tiger), van Leeuwen, E.M. (Elisabeth), Nickels, S. (Stefan), Sanfilippo, P. (Paul), Liao, J. (Jiemin), Linde, H.V. (Herma van der), Zhao, W. (Wanting), van Koolwijk, L.M. (Leonieke), Zheng, L. (Li), Rivadeneira, F. (Fernando), Baskaran, M. (Mani), van der Lee, S.J. (Sven), Perera, S. (Shamira), de Jong, P.T. (Paulus), Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Fan, Q. (Qiao), Hofman, A. (Albert), Shyong Tai, E. (E-), Vingerling, J.R. (Johannes), Sim, X. (Xueling), Wolfs, R.C. (Roger), Teo, Y.Y. (Yik Ying), Lemij, H.G. (Hans), Khor, C.C. (Chiea Chuen), Willemsen, R. (Rob), Lackner, K.J. (Karl), Aung, T. (Tin), Jansonius, N.M. (Nomdo), Montgomery, G. (Grant), Wild, P.S. (Philipp), Young, T.L. (Terri), Burdon, K.P. (Kathryn), Hysi, P.G. (Pirro), Pasquale, L.R. (Louis), Wong, T.Y. (Tien Yin), Klaver, C.C. (Caroline), Hewitt, A.W. (Alex), Jonas, J.B. (Jost), Mitchell, P. (Paul), Lotery, A.J. (Andrew), Foster, P.J. (Paul), Vitart, V. (Veronique), Pfeiffer, N. (Norbert), Craig, J.E. (Jamie), Mackey, D.A. (David), Hammond, C.J. (Christopher), Wiggs, J.L. (Janey), Cheng, C.Y. (Ching-Yu), van Duijn, C.M. (Cornelia), MacGregor, S. (Stuart), Springelkamp, H. (Henriët), Iglesias, A.I. (Adriana), Mishra, A. (Aniket), Höhn, R. (René), Wojciechowski, R. (Robert), Khawaja, A.P. (Anthony), Nag, A. (Abhishek), Wang, Y.X. (Ya Xing), Wang, J.J. (Jie Jin), Cuellar-Partida, G. (Gabriel), Gibson, J. (Jane), Cooke Bailey, J.N. (Jessica), Vithana, E.N. (Eranga), Gharahkhani, P. (Puya), Boutin, T. (Thibaud), Ramdas, W.D. (Wishal), Zeller, T. (Tanja), Luben, R.N. (Robert), Yonova-Doing, E. (Ekaterina), Viswanathan, A.C. (Ananth), Yazar, S. (Seyhan), Cree, A.J. (Angela), Haines, J.L. (Jonathan), Koh, J.Y. (Jia Yu), Souzeau, E. (Emmanuelle), Wilson, J.F. (James), Amin, N. (Najaf), Müller, C. (Christian), Venturini, C. (Cristina), Kearns, L.S. (Lisa), Hee Kang, J. (Jae), Consortium, N. (Neighborhood), Tham, Y.C. (Yih Chung), Zhou, T. (Tiger), van Leeuwen, E.M. (Elisabeth), Nickels, S. (Stefan), Sanfilippo, P. (Paul), Liao, J. (Jiemin), Linde, H.V. (Herma van der), Zhao, W. (Wanting), van Koolwijk, L.M. (Leonieke), Zheng, L. (Li), Rivadeneira, F. (Fernando), Baskaran, M. (Mani), van der Lee, S.J. (Sven), Perera, S. (Shamira), de Jong, P.T. (Paulus), Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Fan, Q. (Qiao), Hofman, A. (Albert), Shyong Tai, E. (E-), Vingerling, J.R. (Johannes), Sim, X. (Xueling), Wolfs, R.C. (Roger), Teo, Y.Y. (Yik Ying), Lemij, H.G. (Hans), Khor, C.C. (Chiea Chuen), Willemsen, R. (Rob), Lackner, K.J. (Karl), Aung, T. (Tin), Jansonius, N.M. (Nomdo), Montgomery, G. (Grant), Wild, P.S. (Philipp), Young, T.L. (Terri), Burdon, K.P. (Kathryn), Hysi, P.G. (Pirro), Pasquale, L.R. (Louis), Wong, T.Y. (Tien Yin), Klaver, C.C. (Caroline), Hewitt, A.W. (Alex), Jonas, J.B. (Jost), Mitchell, P. (Paul), Lotery, A.J. (Andrew), Foster, P.J. (Paul), Vitart, V. (Veronique), Pfeiffer, N. (Norbert), Craig, J.E. (Jamie), Mackey, D.A. (David), Hammond, C.J. (Christopher), Wiggs, J.L. (Janey), Cheng, C.Y. (Ching-Yu), van Duijn, C.M. (Cornelia), and MacGregor, S. (Stuart)

Abstract

Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increase risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed so far. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG risk.

Published
2017
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6. Incidence of glaucomatous visual field loss after two decades of follow-up: the Rotterdam Study

Author

Springelkamp, H. (Henriët), Wolfs, R.C.W. (Roger), Ramdas, W.D. (Wishal), Hofman, A. (Albert), Vingerling, J.R. (Hans), Klaver, C.C.W. (Caroline), Jansonius, N.M. (Nomdo), Springelkamp, H. (Henriët), Wolfs, R.C.W. (Roger), Ramdas, W.D. (Wishal), Hofman, A. (Albert), Vingerling, J.R. (Hans), Klaver, C.C.W. (Caroline), and Jansonius, N.M. (Nomdo)

Abstract

To determine the incidence of glaucomatous visual field loss (GVFL) two decades after the start of the Rotterdam Study, and to compare known risk factors for open-angle glaucoma (OAG) between different clinical manifestations of OAG. Of 6806 participants aged 55 years and older from the population-based Rotterdam Study, 3939 underwent visual field testing at baseline and at least one follow-up round. The ophthalmic examinations included optic disc assessment and measurements of intraocular pressure (IOP), refractive error, diastolic blood pressure (DBP), and height and weight. The incidence rate of GVFL was calculated. Associations with the risk factors age, gender, baseline IOP, family history, myopia, DBP, and body-mass index [BMI] were assessed using Cox regression, with different clinical manifestations of OAG as outcome measure (glaucomatous optic neuropathy (GON), GVFL, GVFL and GON, GVFL without GON, and GON without GVFL). Median follow-up was 11.1 (IQR 6.8–17.2; range 5.0–20.3) years. The incidence rate of GVFL was 2.9 (95% confidence interval 2.4–3.4) per 1000 person years (140 case

Published
2017
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7. 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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8. Open-angle glaucoma

Author

Springelkamp, H. (Henriët) and Springelkamp, H. (Henriët)

Abstract

Open-angle glaucoma (OAG) is an important cause of irreversible blindness. In OAG, loss of retinal ganglion cells leads to damage of the optic nerve. This causes visual field loss and eventually blindness. Changes in the optic nerve head (ONH) can be examined with confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph [HRT]), scanning laser polarimetry (GDx) or Optical Coherence Tomography (OCT). Important risk factors for OAG are elevated intraocular pressure (IOP), high age, myopia, ethnicity, thin central corneal thickness, and a positive family history for OAG. However, the pathophysiology still remains largely unknown. In order to improve the diagnosis and learn more about the pathophysiology of this blinding disease, the main objectives of the research described in this thesis were to: 1) address the diagnostic utility of the OCT scan for OAG, 2) elucidate new risk factors for OAG or IOP, 3) identify novel genetic variants associated with OAG or its endophenotypes, and 4) assess the functional consequences of genetic variants associated with OAG. Our study populations included the population-based Rotterdam Study, the Erasmus Rucphen Family (ERF) Study, population-based studies from the European Eye Epidemiology (E3) Consortium and population-based and OAG case-control studies from the International Glaucoma Genetics Consortium (IGGC).

Published
2016

9. Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology

Author

Springelkamp, H. (Henriët), Mishra, A. (Aniket), Hysi, P.G. (Pirro), Gharahkhani, P. (Puya), Höhn, R. (René), Khor, C.C., Cooke Bailey, J.N. (Jessica N.), Luo, X. (Xiaoyan), Ramdas, W.D. (Wishal), Vithana, E.N. (Eranga), Koh, V. (Victor), Yazar, S. (Seyhan), Xu, L. (Liang), Forward, H. (Hannah), Kearns, L.S. (Lisa S.), Amin, N. (Najaf), Iglesias González, A.I. (Adriana), Sim, K.S., Leeuwen, E.M. (Elisa) van, Demirkan, A. (Ayşe), Lee, S.J. (Sven) van der, Loon, S.-C. (Seng-Chee), Rivadeneira Ramirez, F. (Fernando), Nag, A. (Abhishek), Sanfilippo, P.G. (Paul G.), Schillert, A. (Arne), Jong, P.T.V.M. (Paulus) de, Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Hofman, A. (Albert), Zhou, T. (Tiger), Burdon, K.P. (Kathryn), Spector, T.D. (Timothy), Lackner, K.J. (Karl), Saw, S-M. (Seang-Mei), Vingerling, J.R. (Hans), Teo, Y.Y. (Yik Ying), Pasquale, L.R. (Louis), Wolfs, R.C.W. (Roger), Lemij, H.G. (Hans), Tai, E.S. (Shyong), Jonas, J.B. (Jost B.), Cheng, C-Y. (Ching-Yu), Aung, T. (Tin), Jansonius, N.M. (Nomdo), Klaver, C.C.W. (Caroline), Craig, J.E. (Jamie), Young, T.L. (Terri), Haines, J.L. (Jonathan), MacGregor, S. (Stuart), Mackey, D.A. (David), Pfeiffer, A.F.H. (Andreas), Wong, T.Y. (Tien Yin), Wiggs, J.L. (Janey), Hewit, A.W. (Alex), Duijn, C.M. (Cornelia) van, Hammond, C.J. (Christopher), Springelkamp, H. (Henriët), Mishra, A. (Aniket), Hysi, P.G. (Pirro), Gharahkhani, P. (Puya), Höhn, R. (René), Khor, C.C., Cooke Bailey, J.N. (Jessica N.), Luo, X. (Xiaoyan), Ramdas, W.D. (Wishal), Vithana, E.N. (Eranga), Koh, V. (Victor), Yazar, S. (Seyhan), Xu, L. (Liang), Forward, H. (Hannah), Kearns, L.S. (Lisa S.), Amin, N. (Najaf), Iglesias González, A.I. (Adriana), Sim, K.S., Leeuwen, E.M. (Elisa) van, Demirkan, A. (Ayşe), Lee, S.J. (Sven) van der, Loon, S.-C. (Seng-Chee), Rivadeneira Ramirez, F. (Fernando), Nag, A. (Abhishek), Sanfilippo, P.G. (Paul G.), Schillert, A. (Arne), Jong, P.T.V.M. (Paulus) de, Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Hofman, A. (Albert), Zhou, T. (Tiger), Burdon, K.P. (Kathryn), Spector, T.D. (Timothy), Lackner, K.J. (Karl), Saw, S-M. (Seang-Mei), Vingerling, J.R. (Hans), Teo, Y.Y. (Yik Ying), Pasquale, L.R. (Louis), Wolfs, R.C.W. (Roger), Lemij, H.G. (Hans), Tai, E.S. (Shyong), Jonas, J.B. (Jost B.), Cheng, C-Y. (Ching-Yu), Aung, T. (Tin), Jansonius, N.M. (Nomdo), Klaver, C.C.W. (Caroline), Craig, J.E. (Jamie), Young, T.L. (Terri), Haines, J.L. (Jonathan), MacGregor, S. (Stuart), Mackey, D.A. (David), Pfeiffer, A.F.H. (Andreas), Wong, T.Y. (Tien Yin), Wiggs, J.L. (Janey), Hewit, A.W. (Alex), Duijn, C.M. (Cornelia) van, and Hammond, C.J. (Christopher)

Abstract

Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asian ancestry. The outcomes of the genome-wide association studies were disc area and cup area. These specific measurements describe optic nerve morphology in another way than the vertical cup-disc ratio, which is a clinically used measurement, and may shed

Published
2015
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10. Validity of automated choroidal segmentation in SS-OCT and SD-OCT

Author

Zhang, L. (Li), Buitendijk, G.H.S. (Gabrielle), Lee, K. (Kyungmoo), Sonka, M. (Milan), Springelkamp, H. (Henriët), Hofman, A. (Albert), Vingerling, J.R. (Hans), Mullins, R.F. (Robert F.), Klaver, C.C.W. (Caroline), Abràmoff, M.D. (Michael), Zhang, L. (Li), Buitendijk, G.H.S. (Gabrielle), Lee, K. (Kyungmoo), Sonka, M. (Milan), Springelkamp, H. (Henriët), Hofman, A. (Albert), Vingerling, J.R. (Hans), Mullins, R.F. (Robert F.), Klaver, C.C.W. (Caroline), and Abràmoff, M.D. (Michael)

Abstract

PURPOSE. To evaluate the validity of a novel fully automated three-dimensional (3D) method capable of segmenting the choroid from two different optical coherence tomography scanners: swept-source OCT (SS-OCT) and spectral-domain OCT (SD-OCT). METHODS. One hundred eight subjects were imaged using SS-OCT and SD-OCT. A 3D method was used to segment the choroid and quantify the choroidal thickness along each A-scan. The segmented choroidal posterior boundary was evaluated by comparing to manual segmentation. Differences were assessed to test the agreement between segmentation results of the same subject. Choroidal thickness was defined as the Euclidian distance between Bruch’s membrane and the choroidal posterior boundary, and reproducibility was analyzed using automatically and manually determined choroidal thicknesses. RESULTS. For SS-OCT, the average choroidal thickness of the entire 6-by 6-mm2 macular region was 219.5 lm (95% confidence interval [CI], 204.9–234.2 µm), and for SD-OCT it was 209.5 µm (95% CI, 197.9–221.0 µm). The agreement between automated and manual segmentations was high: Average relative difference was less than 5 lm, and average absolute difference was less than 15 µm. Reproducibility of choroidal thickness between repeated SS-OCT scans was high (coefficient of variation [CV] of 3.3%, intraclass correlation coefficient [ICC] of 0.98), and differences between SS-OCT and SD-OCT results were small (CV of 11.0%, ICC of 0.73). CONCLUSIONS. We have developed a fully automated 3D method for segmenting the choroid and quantifying choroidal thickness along each A-scan. The method yielded high validity. Our method can be used reliably to study local choroidal changes and may improve the diagnosis and management of patients with ocular diseases in which the choroid is affected.

Published
2015
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11. Population-based evaluation of retinal nerve fiber layer, Retinal ganglion cell layer, And inner plexiform layer as a diagnostic tool for glaucoma

Author

Springelkamp, H. (Henriët), Lee, K. (Kyungmoo), Wolfs, R.C.W. (Roger), Buitendijk, G.H.S. (Gabrielle), Ramdas, W.D. (Wishal), Hofman, A. (Albert), Vingerling, J.R. (Hans), Klaver, C.C.W. (Caroline), Abràmoff, M.D. (Michael), Jansonius, N.M. (Nomdo), Springelkamp, H. (Henriët), Lee, K. (Kyungmoo), Wolfs, R.C.W. (Roger), Buitendijk, G.H.S. (Gabrielle), Ramdas, W.D. (Wishal), Hofman, A. (Albert), Vingerling, J.R. (Hans), Klaver, C.C.W. (Caroline), Abràmoff, M.D. (Michael), and Jansonius, N.M. (Nomdo)

Abstract

PURPOSE. We determined the glaucoma screening performance of regional optical coherence tomography (OCT) layer thickness measurements in the peripapillary and macular region, in a population-based setting.METHODS. Subjects (n = 1224) in the Rotterdam Study underwent visual field testing (Humphrey Field Analyzer) and OCT of the macula and optic nerve head (Topcon 3-D OCT- 1000). We determined the mean thi

Published
2014
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12. Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma

Author

Hysi, P.G. (Pirro), Cheng, C-Y. (Ching-Yu), Springelkamp, H. (Henriët), MacGregor, S. (Stuart), Bailey, J.N.C. (Jessica N. Cooke), Wojciechowski, R. (Robert), Vitart, V. (Veronique), Nag, A. (Abhishek), Hewit, A.W. (Alex), Höhn, R. (René), Venturini, C. (Cristina), Mirshahi, A. (Alireza), Ramdas, W.D. (Wishal), Thorleifsson, G. (Gudmar), Vithana, E.N. (Eranga), Khor, C.C., Stefansson, A.B. (Arni B.), Liao, J. (Jie), Haines, J.L. (Jonathan), Amin, N. (Najaf), Wang, Y. (Ying), Wild, P.S. (Philipp S.), Ozel, A.B. (Ayse), Li, J., Fleck, B.W. (Brian W.), Zeller, T. (Tanja), Staffieri, S.E. (Sandra E.), Teo, Y.Y. (Yik Ying), Cuellar-Partida, G. (Gabriel), Luo, X. (Xiaoyan), Allingham, R.R. (R Rand), Richards, J.E. (Julia), Senft, A. (Andrea), Karssen, L.C. (Lennart), Zheng, Y. (Yingfeng), Bellenguez, C. (Céline), Xu, L. (Liang), Iglesias González, A.I. (Adriana), Wilson, J.F. (James F), Kang, J.H. (Jae), Leeuwen, E.M. (Elisa) van, Jonsson, V. (Vesteinn), Thorsteinsdottir, U. (Unnur), Despriet, D.D.G. (Dominique), Ennis, S. (Sarah), Moroi, S.E. (Sayoko), Martin, N.G. (Nicholas), Jansonius, N.M. (Nomdo), Yazar, S. (Seyhan), Tai, E.S. (Shyong), Amouyel, P. (Philippe), Kirwan, J. (James), Koolwijk, L.M.E. (Leonieke) van, Hauser, M.A. (Michael), Jonasson, F. (Fridbert), Leo, P.J. (Paul), Loomis, S.J. (Stephanie J.), Fogarty, R. (Rhys), Rivadeneira Ramirez, F. (Fernando), Kearns, L.S. (Lisa S.), Lackner, K.J. (Karl), Jong, P.T.V.M. (Paulus) de, Simpson, C.L. (Claire), Pennell, C.E. (Craig), Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Saw, S-M. (Seang-Mei), Lotery, A.J. (Andrew), Bailey-Wilson, J.E. (Joan E.), Hofman, A. (Albert), Vingerling, J.R. (Hans), Maubaret, C. (Cécilia), Pfeiffer, A.F.H. (Andreas), Wolfs, R.C.W. (Roger), Lemij, H.G. (Hans), Young, T.L. (Terri), Pasquale, L.R. (Louis), Delcourt, C. (Cécile), Spector, T.D. (Timothy), Klaver, C.C.W. (Caroline), Small, K.S. (Kerrin), Burdon, K.P. (Kathryn), Zwart, J-A. (John-Anker), Wong, T.Y. (Tien Yin), Viswanathan, A.C. (Ananth), Mackey, D.A. (David), Craig, J.E. (Jamie), Wiggs, J.L. (Janey), Duijn, C.M. (Cornelia) van, Hammond, C.J. (Christopher), Aung, T. (Tin), Hysi, P.G. (Pirro), Cheng, C-Y. (Ching-Yu), Springelkamp, H. (Henriët), MacGregor, S. (Stuart), Bailey, J.N.C. (Jessica N. Cooke), Wojciechowski, R. (Robert), Vitart, V. (Veronique), Nag, A. (Abhishek), Hewit, A.W. (Alex), Höhn, R. (René), Venturini, C. (Cristina), Mirshahi, A. (Alireza), Ramdas, W.D. (Wishal), Thorleifsson, G. (Gudmar), Vithana, E.N. (Eranga), Khor, C.C., Stefansson, A.B. (Arni B.), Liao, J. (Jie), Haines, J.L. (Jonathan), Amin, N. (Najaf), Wang, Y. (Ying), Wild, P.S. (Philipp S.), Ozel, A.B. (Ayse), Li, J., Fleck, B.W. (Brian W.), Zeller, T. (Tanja), Staffieri, S.E. (Sandra E.), Teo, Y.Y. (Yik Ying), Cuellar-Partida, G. (Gabriel), Luo, X. (Xiaoyan), Allingham, R.R. (R Rand), Richards, J.E. (Julia), Senft, A. (Andrea), Karssen, L.C. (Lennart), Zheng, Y. (Yingfeng), Bellenguez, C. (Céline), Xu, L. (Liang), Iglesias González, A.I. (Adriana), Wilson, J.F. (James F), Kang, J.H. (Jae), Leeuwen, E.M. (Elisa) van, Jonsson, V. (Vesteinn), Thorsteinsdottir, U. (Unnur), Despriet, D.D.G. (Dominique), Ennis, S. (Sarah), Moroi, S.E. (Sayoko), Martin, N.G. (Nicholas), Jansonius, N.M. (Nomdo), Yazar, S. (Seyhan), Tai, E.S. (Shyong), Amouyel, P. (Philippe), Kirwan, J. (James), Koolwijk, L.M.E. (Leonieke) van, Hauser, M.A. (Michael), Jonasson, F. (Fridbert), Leo, P.J. (Paul), Loomis, S.J. (Stephanie J.), Fogarty, R. (Rhys), Rivadeneira Ramirez, F. (Fernando), Kearns, L.S. (Lisa S.), Lackner, K.J. (Karl), Jong, P.T.V.M. (Paulus) de, Simpson, C.L. (Claire), Pennell, C.E. (Craig), Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Saw, S-M. (Seang-Mei), Lotery, A.J. (Andrew), Bailey-Wilson, J.E. (Joan E.), Hofman, A. (Albert), Vingerling, J.R. (Hans), Maubaret, C. (Cécilia), Pfeiffer, A.F.H. (Andreas), Wolfs, R.C.W. (Roger), Lemij, H.G. (Hans), Young, T.L. (Terri), Pasquale, L.R. (Louis), Delcourt, C. (Cécile), Spector, T.D. (Timothy), Klaver, C.C.W. (Caroline), Small, K.S. (Kerrin), Burdon, K.P. (Kathryn), Zwart, J-A. (John-Anker), Wong, T.Y. (Tien Yin), Viswanathan, A.C. (Ananth), Mackey, D.A. (David), Craig, J.E. (Jamie), Wiggs, J.L. (Janey), Duijn, C.M. (Cornelia) van, Hammond, C.J. (Christopher), and Aung, T. (Tin)

Abstract

Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 × 10 '8 for rs6445055), two on chromosome 9 (P = 2.80 × 10 '11 for rs2472493 near ABCA1 and P = 6.39 × 10 '11 for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 × 10 '11 for rs747782). Separate meta-analyses of 4 independent POAG cohorts, totaling 4,284 cases and 95,560 controls, showed that 3 of these loci for IOP were also associated with POAG.

Published
2014
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13. Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

Author

Springelkamp, H. (Henriët), Höhn, R. (René), Mishra, A. (Aniket), Hysi, P.G. (Pirro), Khor, C.C., Loomis, S.J. (Stephanie J.), Bailey, J.N.C. (Jessica N. Cooke), Gibson, J. (Jane), Thorleifsson, G. (Gudmar), Janssen, S.F. (Sarah), Luo, X. (Xiaoyan), Ramdas, W.D. (Wishal), Vithana, E.N. (Eranga), Nongpiur, M.E. (Monisha E.), Montgomery, G.W. (Grant), Xu, L. (Liang), Mountain, J.E. (Jenny E.), Gharahkhani, P. (Puya), Lu, Y. (Yi), Amin, N. (Najaf), Karssen, L.C. (Lennart), Sim, K.S., Leeuwen, E.M. (Elisa) van, Iglesias González, A.I. (Adriana), Verhoeven, V.J.M. (Virginie), Hauser, M.A. (Michael), Loon, S.-C. (Seng-Chee), Despriet, D.D.G. (Dominique), Nag, A. (Abhishek), Venturini, C. (Cristina), Sanfilippo, P.G. (Paul G.), Schillert, A. (Arne), Kang, J.H. (Jae), Landers, J. (John), Jonasson, F. (Fridbert), Cree, A.J. (Angela), Koolwijk, L.M.E. (Leonieke) van, Rivadeneira Ramirez, F. (Fernando), Souzeau, E. (Emmanuelle), Jonsson, V. (Vesteinn), Menon, G. (Geeta), Mitchell, P. (Paul), Wang, J.J. (Jie Jin), Rochtchina, E. (Elena), Attia, J. (John), Scott, R. (Rodney), Holliday, E.G. (Elizabeth), Baird, P.N. (Paul), Xie, J. (Jing), Inouye, M. (Michael), Viswanathan, A.C. (Ananth), Sim, X. (Xueling), Weinreb, R.N. (Robert N.), Jong, P.T.V.M. (Paulus) de, Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Hofman, A. (Albert), Ennis, S. (Sarah), Thorsteinsdottir, U. (Unnur), Burdon, K.P. (Kathryn), Spector, T.D. (Timothy), Mirshahi, A. (Alireza), Saw, S-M. (Seang-Mei), Vingerling, J.R. (Hans), Teo, Y.Y. (Yik Ying), Wolfs, R.C.W. (Roger), Lemij, H.G. (Hans), Tai, E.S. (Shyong), Jansonius, N.M. (Nomdo), Jonas, J.B. (Jost B.), Cheng, C-Y. (Ching-Yu), Aung, T. (Tin), Klaver, C.C.W. (Caroline), Craig, J.E. (Jamie), MacGregor, S. (Stuart), Mackey, D.A. (David), Lotery, A.J. (Andrew), Zwart, J-A. (John-Anker), Bergen, A.A.B. (Arthur), Young, T.L. (Terri), Wiggs, J.L. (Janey), Pfeiffer, A.F.H. (Andreas), Wong, T.Y. (Tien Yin), Pasquale, L.R. (Louis), Hewit, A.W. (Alex), Duijn, C.M. (Cornelia) van, Hammond, C.J. (Christopher), Springelkamp, H. (Henriët), Höhn, R. (René), Mishra, A. (Aniket), Hysi, P.G. (Pirro), Khor, C.C., Loomis, S.J. (Stephanie J.), Bailey, J.N.C. (Jessica N. Cooke), Gibson, J. (Jane), Thorleifsson, G. (Gudmar), Janssen, S.F. (Sarah), Luo, X. (Xiaoyan), Ramdas, W.D. (Wishal), Vithana, E.N. (Eranga), Nongpiur, M.E. (Monisha E.), Montgomery, G.W. (Grant), Xu, L. (Liang), Mountain, J.E. (Jenny E.), Gharahkhani, P. (Puya), Lu, Y. (Yi), Amin, N. (Najaf), Karssen, L.C. (Lennart), Sim, K.S., Leeuwen, E.M. (Elisa) van, Iglesias González, A.I. (Adriana), Verhoeven, V.J.M. (Virginie), Hauser, M.A. (Michael), Loon, S.-C. (Seng-Chee), Despriet, D.D.G. (Dominique), Nag, A. (Abhishek), Venturini, C. (Cristina), Sanfilippo, P.G. (Paul G.), Schillert, A. (Arne), Kang, J.H. (Jae), Landers, J. (John), Jonasson, F. (Fridbert), Cree, A.J. (Angela), Koolwijk, L.M.E. (Leonieke) van, Rivadeneira Ramirez, F. (Fernando), Souzeau, E. (Emmanuelle), Jonsson, V. (Vesteinn), Menon, G. (Geeta), Mitchell, P. (Paul), Wang, J.J. (Jie Jin), Rochtchina, E. (Elena), Attia, J. (John), Scott, R. (Rodney), Holliday, E.G. (Elizabeth), Baird, P.N. (Paul), Xie, J. (Jing), Inouye, M. (Michael), Viswanathan, A.C. (Ananth), Sim, X. (Xueling), Weinreb, R.N. (Robert N.), Jong, P.T.V.M. (Paulus) de, Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Hofman, A. (Albert), Ennis, S. (Sarah), Thorsteinsdottir, U. (Unnur), Burdon, K.P. (Kathryn), Spector, T.D. (Timothy), Mirshahi, A. (Alireza), Saw, S-M. (Seang-Mei), Vingerling, J.R. (Hans), Teo, Y.Y. (Yik Ying), Wolfs, R.C.W. (Roger), Lemij, H.G. (Hans), Tai, E.S. (Shyong), Jansonius, N.M. (Nomdo), Jonas, J.B. (Jost B.), Cheng, C-Y. (Ching-Yu), Aung, T. (Tin), Klaver, C.C.W. (Caroline), Craig, J.E. (Jamie), MacGregor, S. (Stuart), Mackey, D.A. (David), Lotery, A.J. (Andrew), Zwart, J-A. (John-Anker), Bergen, A.A.B. (Arthur), Young, T.L. (Terri), Wiggs, J.L. (Janey), Pfeiffer, A.F.H. (Andreas), Wong, T.Y. (Tien Yin), Pasquale, L.R. (Louis), Hewit, A.W. (Alex), Duijn, C.M. (Cornelia) van, and Hammond, C.J. (Christopher)

Abstract

Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition.

Published
2014
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14. Optimizing the information yield of 3-D OCT in glaucoma

Author

Springelkamp, H. (Henriët), Lee, K. (Kyungmoo), Ramdas, W.D. (Wishal), Vingerling, J.R. (Hans), Hofman, A. (Albert), Klaver, C.C.W. (Caroline), Sonka, M. (Milan), Abràmoff, M.D. (Michael), Jansonius, N.M. (Nomdo), Springelkamp, H. (Henriët), Lee, K. (Kyungmoo), Ramdas, W.D. (Wishal), Vingerling, J.R. (Hans), Hofman, A. (Albert), Klaver, C.C.W. (Caroline), Sonka, M. (Milan), Abràmoff, M.D. (Michael), and Jansonius, N.M. (Nomdo)

Abstract

Purpose. To determine, first, which regions of 3-D optical coherence tomography (OCT) volumes can be segmented completely in the majority of subjects and, second, the relationship between analyzed area and thickness measurement test-retest variability. Methods. Three-dimensional OCT volumes (6 × 6 mm) centered around the fovea and optic nerve head (ONH) of 925 Rotterdam Study participants were analyzed; 44 participants were scanned twice. Volumes were segmented into 10 layers, and we determined the area where all layers could be identified in at least 95% (macula) or 90% (ONH) of subjects. Macular volumes were divided in 2 × 2, 4 × 4, 6 × 6, 8 × 8, or 68 blocks. We placed two circles around the ONH; the ONH had to fit into the smaller circle, and the larger circle had to fit into the segmentable part of the volume. The area between the circles was divided in 3 to 12 segments. We determined the test-retest variability (coefficient of repeatability) of the retinal nerve fiber layer (RNFL) and ganglion cell layer (RGCL) thickness measurements as a function of size of blocks/segments. Results. Eighty-two percent of the macular volume could be segmented in at least 95% of subjects; for the ONH, this was 65% in at least 90%. The radii of the circles were 1.03 and 1.84 mm. Depending on the analyzed area, median test-retest variability ranged from 8% to 15% for macular RNFL, 11% to 22% for macular RGCL, 5% to 11% for the two together, and 18% to 22% for ONH RNFL. Conclusions. Test-retest variability hampers a detailed analysis of 3-D OCT data. Combined macular RNFL and RGCL thickness averaged over larger areas had the best test-retest variability.

Published
2012
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