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2. Variation in eye care professional distribution across Europe, a survey

Author

Arnould, Louis, Varsanyi, Balazs, Dervan, Edward, Posarelli, Chiara, Filipe, Helena Prior, Bourcier, Tristan, Wedrich, Andreas, Ivekovic, Renata, Petrovski, Goran, Porro, Giorgio L., Laganovska, Guna, Balciuniene, Vilma Jurate, Mrukwa-Kominek, Ewa, Paust, Karsten, Roemer, Segolene, Haefliger, Ivan O., Atilla, Huban, Ursell, Paul, Cvenkel, Barba, Kiilgaard, Jens, Grupcheva, Christina, Furdova, Alena, Claeys, Marnix, Maresova, Klara, Mercieca, Franco, Sepp, Toomas, Parikakis, Efstratios, Burcea, Marian, Aclimandos, Wagih, and Khawaja, Anthony P.

Published
2024
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4. Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma

Author

Hamel, Andrew R., Yan, Wenjun, Rouhana, John M., Monovarfeshani, Aboozar, Jiang, Xinyi, Mehta, Puja A., Advani, Jayshree, Luo, Yuyang, Liang, Qingnan, Rajasundaram, Skanda, Shrivastava, Arushi, Duchinski, Katherine, Mantena, Sreekar, Wang, Jiali, van Zyl, Tavé, Pasquale, Louis R., Swaroop, Anand, Gharahkhani, Puya, Khawaja, Anthony P., MacGregor, Stuart, Chen, Rui, Vitart, Veronique, Sanes, Joshua R., Wiggs, Janey L., and Segrè, Ayellet V.

Published
2024
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6. The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population

Author

Aschard, Hugues, Chia, Mark, Chua, Sharon, Do, Ron, Foster, Paul, Kang, Jae, Kastner, Alan, Khawaja, Anthony, Kim, Jihye, Lentjes, Marleen, Luben, Robert, Madjedi, Kian, Montesano, Giovanni, Pasquale, Louis, Stuart, Kelsey, Warwick, Alasdair, Wiggs, Janey, Allen, Naomi, Aslam, Tariq, Atan, Denize, Barman, Sarah, Barrett, Jenny, Bishop, Paul, Black, Graeme, Braithwaite, Tasanee, Carare, Roxana, Chakravarthy, Usha, Chan, Michelle, Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew, Doney, Alexander, Egan, Cathy, Ennis, Sarah, Fruttiger, Marcus, Garway-Heath, David (Ted), Gibson, Jane, Guggenheim, Jeremy, Hammond, Chris, Hardcastle, Alison, Harding, Simon, Hogg, Ruth, Hysi, Pirro, Keane, Pearse, Khaw, Peng Tee, Lascaratos, Gerassimos, Littlejohns, Thomas, Lotery, Andrew, Luthert, Phil, MacGillivray, Tom, Mackie, Sarah, McGuinness, Bernadette, McKay, Gareth, McKibbin, Martin, Moore, Tony, Morgan, James, O'Sullivan, Eoin, Oram, Richard, Owen, Chris, Patel, Praveen, Paterson, Euan, Peto, Tunde, Petzold, Axel, Pontikos, Nikolas, Rahi, Jugnoo, Rudnicka, Alicja, Sattar, Naveed, Self, Jay, Sergouniotis, Panagiotis, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Strouthidis, Nicholas, Sudlow, Cathie, Sun, Zihan, Tapp, Robyn, Thomas, Dhanes, Trucco, Emanuele, Tufail, Adnan, Viswanathan, Ananth, Vitart, Veronique, Weedon, Mike, Williams, Katie, Williams, Cathy, Woodside, Jayne, Yates, Max, Yip, Jennifer, Zheng, Yalin, Aung, Tin, Burdon, Kathryn, Chen, Li, Cheng, Ching-Yu, Craig, Jamie, Cree, Angela, de Vries, Victor, Driessen, Sjoerd, Fingert, John, Gharahkhani, Puya, Hammond, Christopher, Hayward, Caroline, Hewitt, Alex, Jansonius, Nomdo, Jonansson, Fridbert, Jonas, Jost, Kass, Michael, Khor, Chiea, Klaver, Caroline, Koh, Jacyline, MacGregor, Stuart, Mackey, David, Mitchell, Paul, Pang, Calvin, Pasutto, Francesca, Pfeiffer, Norbert, Polašek, Ozren, Ramdas, Wishal, Schuster, Alexander, Segrè, Ayellet, Stefansson, Einer, Stefánsson, Kári, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, van Duijn, Cornelia, Vergroesen, Joëlle, Vithana, Eranga, Wilson, James, Wojciechowski, Robert, Wong, Tien, Young, Terri, Stuart, Kelsey V., Biradar, Mahantesh I., Luben, Robert N., Dhaun, Neeraj, Wagner, Siegfried K., Warwick, Alasdair N., Madjedi, Kian M., Pasquale, Louis R., Wiggs, Janey L., Kang, Jae H., Lentjes, Marleen A.H., Foster, Paul J., and Khawaja, Anthony P.

Published
2024
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7. Periodontitis and Outer Retinal Thickness: a Cross-Sectional Analysis of the United Kingdom Biobank Cohort

Author

Allen, Naomi, Aslam, Tariq, Atan, Denize, Balaskas, Konsantinos, Barman, Sarah A., Barrett, Jenny H., Bishop, Paul, Black, Graeme, Braithwaite, Tasanee, Carare, Roxana O., Chakravarthy, Usha, Chan, Michelle, Chua, Sharon Y.L., Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew D., Doney, Alexander, Egan, Cathy, Ennis, Sarah, Foster, Paul, Fruttiger, Marcus, Gallacher, John E.J., Garway-Heath, David F., Gibson, Jane, Guggenheim, Jeremy A., Hammond, Chris J., Hardcastle, Alison, Harding, Simon P., Hogg, Ruth E., Hysi, Pirro, Keane, Pearse A., Khaw, Sir Peng T., Khawaja, Anthony P., Lascaratos, Gerassimos, Littlejohns, Thoams, Lotery, Andrew J., Luben, Robert, Luthert, Phil, Macgillivray, Tom, Mackie, Sarah, McGuinness, Bernadette, McKay, Gareth J., McKibbin, Martin, Moore, Tony, Morgan, James E., O’Sullivan, Eoin, Oram, Richard, Owen, Chris G., Patel, Praveen, Paterson, Euan, Peto, Tunde, Petzold, Axel, Rahi, Jugnoo S., Rudnikca, Alicja R., Sattar, Naveed, Self, Jay, Sergouniotis, Panagiotis, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Strouthidis, Nicholas, Sudlow, Cathie, Sun, Zihan, Tapp, Robyn, Thomas, Dhanes, Trucco, Emanuele, Tufail, Adnan, Vitart, Veronique, Viswanathan, Ananth C., Weedon, Mike, Williams, Cathy, Williams, Katie, Woodside, Jayne V., Yates, Max M., Yip, Jennifer, Zheng, Yalin, Wagner, Siegfried K., Patel, Praveen J., Huemer, Josef, Khalid, Hagar, Stuart, Kelsey V., Chu, Colin J., Williamson, Dominic J., Struyven, Robbert R., Romero-Bascones, David, Foster, Paul J., Balaskas, Konstantinos, Cortina-Borja, Mario, Chapple, Iain, Dietrich, Thomas, and Denniston, Alastair K.

Published
2024
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9. Rare variant analyses across multiethnic cohorts identify novel genes for refractive error

Author

Musolf, Anthony M., Haarman, Annechien E. G., Luben, Robert N., Ong, Jue-Sheng, Patasova, Karina, Trapero, Rolando Hernandez, Marsh, Joseph, Jain, Ishika, Jain, Riya, Wang, Paul Zhiping, Lewis, Deyana D., Tedja, Milly S., Iglesias, Adriana I., Li, Hengtong, Cowan, Cameron S., Biino, Ginevra, Klein, Alison P., Duggal, Priya, Mackey, David A., Hayward, Caroline, Haller, Toomas, Metspalu, Andres, Wedenoja, Juho, Pärssinen, Olavi, Cheng, Ching-Yu, Saw, Seang-Mei, Stambolian, Dwight, Hysi, Pirro G., Khawaja, Anthony P., Vitart, Veronique, Hammond, Christopher J., van Duijn, Cornelia M., Verhoeven, Virginie J. M., Klaver, Caroline C. W., and Bailey-Wilson, Joan E.

Published
2023
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11. Large-scale multitrait genome-wide association analyses identify hundreds of glaucoma risk loci

Author

Han, Xikun, Gharahkhani, Puya, Hamel, Andrew R., Ong, Jue Sheng, Rentería, Miguel E., Mehta, Puja, Dong, Xianjun, Pasutto, Francesca, Hammond, Christopher, Young, Terri L., Hysi, Pirro, Lotery, Andrew J., Jorgenson, Eric, Choquet, Hélène, Hauser, Michael, Cooke Bailey, Jessica N., Nakazawa, Toru, Akiyama, Masato, Shiga, Yukihiro, Fuller, Zachary L., Wang, Xin, Hewitt, Alex W., Craig, Jamie E., Pasquale, Louis R., Mackey, David A., Wiggs, Janey L., Khawaja, Anthony P., Segrè, Ayellet V., and MacGregor, Stuart

Published
2023
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13. Large-scale machine learning-based phenotyping significantly improves genomic discovery for optic nerve head morphology

Author

Alipanahi, Babak, Hormozdiari, Farhad, Behsaz, Babak, Cosentino, Justin, McCaw, Zachary R., Schorsch, Emanuel, Sculley, D., Dorfman, Elizabeth H., Phene, Sonia, Hammel, Naama, Carroll, Andrew, Khawaja, Anthony P., and McLean, Cory Y.

Subjects
Quantitative Biology - Genomics, Statistics - Applications
Abstract

Genome-wide association studies (GWAS) require accurate cohort phenotyping, but expert labeling can be costly, time-intensive, and variable. Here we develop a machine learning (ML) model to predict glaucomatous optic nerve head features from color fundus photographs. We used the model to predict vertical cup-to-disc ratio (VCDR), a diagnostic parameter and cardinal endophenotype for glaucoma, in 65,680 Europeans in the UK Biobank (UKB). A GWAS of ML-based VCDR identified 299 independent genome-wide significant (GWS; $P\leq5\times10^{-8}$) hits in 156 loci. The ML-based GWAS replicated 62 of 65 GWS loci from a recent VCDR GWAS in the UKB for which two ophthalmologists manually labeled images for 67,040 Europeans. The ML-based GWAS also identified 92 novel loci, significantly expanding our understanding of the genetic etiologies of glaucoma and VCDR. Pathway analyses support the biological significance of the novel hits to VCDR, with select loci near genes involved in neuronal and synaptic biology or known to cause severe Mendelian ophthalmic disease. Finally, the ML-based GWAS results significantly improve polygenic prediction of VCDR and primary open-angle glaucoma in the independent EPIC-Norfolk cohort., Comment: Includes Supplementary Information and Tables

Published
2020

15. A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus.

Author

Hardcastle, Alison J, Liskova, Petra, Bykhovskaya, Yelena, McComish, Bennet J, Davidson, Alice E, Inglehearn, Chris F, Li, Xiaohui, Choquet, Hélène, Habeeb, Mahmoud, Lucas, Sionne EM, Sahebjada, Srujana, Pontikos, Nikolas, Lopez, Karla E Rojas, Khawaja, Anthony P, Ali, Manir, Dudakova, Lubica, Skalicka, Pavlina, Van Dooren, Bart TH, Geerards, Annette JM, Haudum, Christoph W, Faro, Valeria Lo, Tenen, Abi, Simcoe, Mark J, Patasova, Karina, Yarrand, Darioush, Yin, Jie, Siddiqui, Salina, Rice, Aine, Farraj, Layal Abi, Chen, Yii-Der Ida, Rahi, Jugnoo S, Krauss, Ronald M, Theusch, Elisabeth, Charlesworth, Jac C, Szczotka-Flynn, Loretta, Toomes, Carmel, Meester-Smoor, Magda A, Richardson, Andrea J, Mitchell, Paul A, Taylor, Kent D, Melles, Ronald B, Aldave, Anthony J, Mills, Richard A, Cao, Ke, Chan, Elsie, Daniell, Mark D, Wang, Jie Jin, Rotter, Jerome I, Hewitt, Alex W, MacGregor, Stuart, Klaver, Caroline CW, Ramdas, Wishal D, Craig, Jamie E, Iyengar, Sudha K, O'Brart, David, Jorgenson, Eric, Baird, Paul N, Rabinowitz, Yaron S, Burdon, Kathryn P, Hammond, Chris J, Tuft, Stephen J, and Hysi, Pirro G

Abstract

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease.

Published
2021

16. Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries.

Author

Gharahkhani, Puya, Jorgenson, Eric, Hysi, Pirro, Khawaja, Anthony P, Pendergrass, Sarah, Han, Xikun, Ong, Jue Sheng, Hewitt, Alex W, Segrè, Ayellet V, Rouhana, John M, Hamel, Andrew R, Igo, Robert P, Choquet, Helene, Qassim, Ayub, Josyula, Navya S, Cooke Bailey, Jessica N, Bonnemaijer, Pieter WM, Iglesias, Adriana, Siggs, Owen M, Young, Terri L, Vitart, Veronique, Thiadens, Alberta AHJ, Karjalainen, Juha, Uebe, Steffen, Melles, Ronald B, Nair, K Saidas, Luben, Robert, Simcoe, Mark, Amersinghe, Nishani, Cree, Angela J, Hohn, Rene, Poplawski, Alicia, Chen, Li Jia, Rong, Shi-Song, Aung, Tin, Vithana, Eranga Nishanthie, NEIGHBORHOOD consortium, ANZRAG consortium, Biobank Japan project, FinnGen study, UK Biobank Eye and Vision Consortium, GIGA study group, 23 and Me Research Team, Tamiya, Gen, Shiga, Yukihiro, Yamamoto, Masayuki, Nakazawa, Toru, Currant, Hannah, Birney, Ewan, Wang, Xin, Auton, Adam, Lupton, Michelle K, Martin, Nicholas G, Ashaye, Adeyinka, Olawoye, Olusola, Williams, Susan E, Akafo, Stephen, Ramsay, Michele, Hashimoto, Kazuki, Kamatani, Yoichiro, Akiyama, Masato, Momozawa, Yukihide, Foster, Paul J, Khaw, Peng T, Morgan, James E, Strouthidis, Nicholas G, Kraft, Peter, Kang, Jae H, Pang, Chi Pui, Pasutto, Francesca, Mitchell, Paul, Lotery, Andrew J, Palotie, Aarno, van Duijn, Cornelia, Haines, Jonathan L, Hammond, Chris, Pasquale, Louis R, Klaver, Caroline CW, Hauser, Michael, Khor, Chiea Chuen, Mackey, David A, Kubo, Michiaki, Cheng, Ching-Yu, Craig, Jamie E, MacGregor, Stuart, and Wiggs, Janey L

Subjects
NEIGHBORHOOD consortium, ANZRAG consortium, Biobank Japan project, FinnGen study, UK Biobank Eye and Vision Consortium, GIGA study group, and Me Research Team, Humans, Glaucoma, Open-Angle, Genetic Predisposition to Disease, Genotype, Polymorphism, Single Nucleotide, Asian Continental Ancestry Group, European Continental Ancestry Group, Genome-Wide Association Study, Genetic Loci, Glaucoma, Open-Angle, Polymorphism, Single Nucleotide
Abstract

Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.

Published
2021

18. The Association of Alcohol Consumption with Glaucoma and Related Traits: Findings from the UK Biobank

Author

Aschard, Hugues, Chia, Mark, Chua, Sharon, Do, Ron, Foster, Paul, Kang, Jae, Kastner, Alan, Khawaja, Anthony, Kim, Jihye, Lentjes, Marleen, Luben, Robert, Madjedi, Kian, Montesano, Giovanni, Pasquale, Louis, Stuart, Kelsey, Warwick, Alasdair, Wiggs, Janey, Allen, Naomi, Aslam, Tariq, Atan, Denize, Barman, Sarah, Barrett, Jenny, Bishop, Paul, Black, Graeme, Braithwaite, Tasanee, Carare, Roxana, Chakravarthy, Usha, Chan, Michelle, Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew, Doney, Alexander, Egan, Cathy, Ennis, Sarah, Fruttiger, Marcus, Gallacher, John, Garway-Heath, David (Ted), Gibson, Jane, Guggenheim, Jeremy, Hammond, Chris, Hardcastle, Alison, Harding, Simon, Hogg, Ruth, Hysi, Pirro, Keane, Pearse, Khaw, Peng Tee, Lascaratos, Gerassimos, Littlejohns, Thomas, Lotery, Andrew, Luthert, Phil, MacGillivray, Tom, Mackie, Sarah, McGuinness, Bernadette, McKay, Gareth, McKibbin, Martin, Moore, Tony, Morgan, James, O'Sullivan, Eoin, Oram, Richard, Owen, Chris, Patel, Praveen, Paterson, Euan, Peto, Tunde, Petzold, Axel, Pontikos, Nikolas, Rahi, Jugnoo, Rudnicka, Alicja, Sattar, Naveed, Self, Jay, Sergouniotis, Panagiotis, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Strouthidis, Nicholas, Sudlow, Cathie, Sun, Zihan, Tapp, Robyn, Thomas, Dhanes, Trucco, Emanuele, Tufail, Adnan, Viswanathan, Ananth, Vitart, Veronique, Weedon, Mike, Williams, Katie, Williams, Cathy, Woodside, Jayne, Yates, Max, Yip, Jennifer, Zheng, Yalin, Aung, Tin, Burdon, Kathryn, Chen, Li, Cheng, Ching-Yu, Craig, Jamie, Cree, Angela, de Vries, Victor, Driessen, Sjoerd, Fingert, John, Gharahkhani, Puya, Hammond, Christopher, Hayward, Caroline, Hewitt, Alex, Jansonius, Nomdo, Jonansson, Fridbert, Jonas, Jost, Kass, Michael, Khor, Chiea, Klaver, Caroline, Koh, Jacyline, MacGregor, Stuart, Mackey, David, Mitchell, Paul, Pang, Calvin, Pasutto, Francesca, Pfeiffer, Norbert, Polašek, Ozren, Ramdas, Wishal, Schuster, Alexander, Segrè, Ayellet, Stefansson, Einer, Stefánsson, Kári, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, van Duijn, Cornelia, Vergroesen, Joëlle, Vithana, Eranga, Wilson, James, Wojciechowski, Robert, Wong, Tien, Young, Terri, Stuart, Kelsey V., Luben, Robert N., Warwick, Alasdair N., Madjedi, Kian M., Patel, Praveen J., Biradar, Mahantesh I., Chia, Mark A., Pasquale, Louis R., Wiggs, Janey L., Kang, Jae H., Tran, Jessica H., Lentjes, Marleen A.H., Foster, Paul J., and Khawaja, Anthony P.

Published
2023
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19. A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration

Author

Bailey-Wilson, Joan E., Baird, Paul N., Barathi, Veluchamy A., Biino, Ginevra, Burdon, Kathryn P., Campbell, Harry, Chen, Li Jia, Cheng, Ching-Yu, Chew, Emily Y., Craig, Jamie E., Deangelis, Margaret M., Delcourt, Cécile, Ding, Xiaohu, Fan, Qiao, Fossarello, Maurizio, Foster, Paul J., Gharahkhani, Puya, Guggenheim, Jeremy A., Guo, Xiaobo, Haarman, Annechien E.G., Haller, Toomas, Hammond, Christopher J., Han, Xikun, Hayward, Caroline, He, Mingguang, Hewitt, Alex W., Hoang, Quan, Hysi, Pirro G., Iglesias, Adriana I., Igo, Robert P., Iyengar, Sudha K., Jonas, Jost B., Kähönen, Mika, Kaprio, Jaakko, Khawaja, Anthony P., Klein, Barbara E., Lass, Jonathan H., Lee, Kris, Lehtimäki, Terho, Lewis, Deyana, Li, Qing, Li, Shi-Ming, Lyytikäinen, Leo-Pekka, MacGregor, Stuart, Mackey, David A., Martin, Nicholas G., Meguro, Akira, Metspalu, Andres, Middlebrooks, Candace, Miyake, Masahiro, Mizuki, Nobuhisa, Musolf, Anthony, Nickels, Stefan, Oexle, Konrad, Pang, Chi Pui, Pärssinen, Olavi, Paterson, Andrew D., Pfeiffer, Norbert, Polasek, Ozren, Rahi, Jugnoo S., Raitakari, Olli, Rudan, Igor, Sahebjada, Srujana, Saw, Seang-Mei, Simpson, Claire L., Stambolian, Dwight, Tai, E-Shyong, Tedja, Milly S., Tideman, J. Willem L., Tsujikawa, Akitaka, van Duijn, Cornelia M., Verhoeven, Virginie J.M., Vitart, Veronique, Wang, Ningli, Wang, Ya Xing, Wedenoja, Juho, Wei, Wen Bin, Williams, Cathy, Williams, Katie M., Wilson, James F., Wojciechowski, Robert, Yam, Jason C.S., Yamashiro, Kenji, Yap, Maurice K.H., Yazar, Seyhan, Yip, Shea Ping, Young, Terri L., Zhou, Xiangtian, Allen, Naomi, Aslam, Tariq, Atan, Denize, Barman, Sarah, Barrett, Jenny, Bishop, Paul, Black, Graeme, Bunce, Catey, Carare, Roxana, Chakravarthy, Usha, Chan, Michelle, Chua, Sharon, Cipriani, Valentina, Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew, Doney, Alexander, Egan, Cathy, Ennis, Sarah, Foster, Paul, Fruttiger, Marcus, Gallacher, John, Garway-Heath, David, Gibson, Jane, Gore, Dan, Guggenheim, Jeremy, Hammond, Chris, Hardcastle, Alison, Harding, Simon, Hogg, Ruth, Hysi, Pirro, Keane, Pearse A., Khaw, Peng Tee, Khawaja, Anthony, Lascaratos, Gerassimos, Littlejohns, Thomas, Lotery, Andrew, Luthert, Phil, MacGillivray, Tom, Mackie, Sarah, McGuinness, Bernadette, McKay, Gareth, McKibbin, Martin, Mitry, Danny, Moore, Tony, Morgan, James, Muthy, Zaynah, O'Sullivan, Eoin, Owen, Chris, Patel, Praveen, Paterson, Euan, Peto, Tunde, Petzold, Axel, Pontikos, Nikolas, Rahi, Jugnoo, Rudnicka, Alicja, Self, Jay, Sergouniotis, Panagiotis, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Strouthidis, Nicholas, Sudlow, Cathie, Tapp, Robyn, Thaung, Caroline, Thomas, Dhanes, Trucco, Emanuele, Tufail, Adnan, Vernon, Stephen, Viswanathan, Ananth, Williams, Katie, Woodside, Jayne, Yates, Max, Yip, Jennifer, Zheng, Yalin, Clark, Rosie, Lee, Samantha Sze-Yee, Du, Ran, Wang, Yining, Kneepkens, Sander C.M., Charng, Jason, Huang, Yu, Hunter, Michael L., Jiang, Chen, Tideman, J.Willem L., Melles, Ronald B., Klaver, Caroline C.W., Choquet, Hélène, and Ohno-Matsui, Kyoko

Published
2023
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20. Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

Author

Bonnemaijer, Pieter WM, Leeuwen, Elisabeth M van, Iglesias, Adriana I, Gharahkhani, Puya, Vitart, Veronique, Khawaja, Anthony P, Simcoe, Mark, Höhn, René, Cree, Angela J, Igo, Rob P, Gerhold-Ay, Aslihan, Nickels, Stefan, Wilson, James F, Hayward, Caroline, Boutin, Thibaud S, Polašek, Ozren, Aung, Tin, Khor, Chiea Chuen, Amin, Najaf, Lotery, Andrew J, Wiggs, Janey L, Cheng, Ching-Yu, Hysi, Pirro G, Hammond, Christopher J, Thiadens, Alberta AHJ, MacGregor, Stuart, Klaver, Caroline CW, and Duijn, Cornelia M van

Subjects
Genetics, Eye Disease and Disorders of Vision, Neurodegenerative, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Case-Control Studies, Computational Biology, Gene Expression Profiling, Genetic Association Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Glaucoma, Humans, Molecular Sequence Annotation, Optic Disk, Optic Nerve Diseases, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Quantitative Trait, Heritable, Signal Transduction, International Glaucoma Genetics Consortium, NEIGHBORHOOD consortium, UK Biobank Eye and Vision Consortium, Genome-wide association studies, Optic nerve diseases
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

23. Conclusion: glaucoma, moving forward

Author

Spaeth, George, primary, Sailer, Kerstin, additional, Gilbert, Clare, additional, Grover, Sumit, additional, Alió, Jorge L., additional, Barrio, Jorge Alio del, additional, Sharma, Anant, additional, Malyugin, Boris, additional, Fellman, Ronald L., additional, Khawaja, Anthony P., additional, Garway-Heath, Ted, additional, and Calkins, David J., additional

Published
2023
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24. List of contributors

Author

Ahmad, Hanif, primary, Alany, Raid G., additional, Alió, Jorge L., additional, Anderson, Andrew J., additional, Arora, Anmol, additional, Azuara-Blanco, Augusto, additional, Barrio, Jorge Alio del, additional, Baudouin, Christophe, additional, Bou Said, Reeda, additional, Bourne, Rupert R.A., additional, Butt, Fatima, additional, Calkins, David J., additional, Chan, Geoffrey Z.P., additional, Cheng, Ching-Yu, additional, Chong, Rachel S., additional, Cordeiro, Maria Francesca, additional, Crowston, Jonathan G., additional, Daka, Qëndresë, additional, Daneshvar, Ramin, additional, Denniss, Jonathan, additional, Deol, Sundeep Singh, additional, Epstein, Rebecca, additional, Ertel, Monica, additional, Fam, Jonathan M., additional, Fellman, Ronald L., additional, Garway-Heath, Ted, additional, Gazzard, Gus, additional, Gilbert, Clare, additional, Gillmann, Kevin, additional, Goldberg, Ivan, additional, Goldberg, Jeffrey L., additional, Grover, Sumit, additional, Heatley, Gregg A., additional, Hoffmann M., Esther, additional, Huang, Alex S., additional, Jin, Zi-Bing, additional, Johnstone, Murray, additional, Kahook, Malik, additional, Katz, L. Jay, additional, Kaufman, Paul L., additional, Keane, Pearse A., additional, Khawaja, Anthony P., additional, Khoueir, Ziad, additional, Lawlor, Mitchell, additional, Leung, Christopher, additional, Malyugin, Boris, additional, Mansberger, Steven L., additional, Mansouri, Kaweh, additional, Martin, Keith R., additional, Martinez, Christine E., additional, McKendrick, Allison M., additional, Mermoud, André, additional, Nickells, Robert W., additional, Nouri-Mahdavi, Kouros, additional, Oostra, Tyler D., additional, Palko, Joel, additional, Patel, Radhika Pooja, additional, Pradhan, Zia S., additional, Priyanka, Ramesh, additional, Rao, Harsha L., additional, Razeghinejad, Reza, additional, Realini, Tony, additional, Ritch, Robert, additional, Roy, Sylvain, additional, Sailer, Kerstin, additional, Sanchez, Facundo G., additional, Schlötzer-Schrehardt, Ursula, additional, Schuman, Joel S., additional, Scott, Andrew, additional, Seibold, Leonard, additional, Sharma, Anant, additional, Spaeth, George, additional, Strohmaier, Clemens A., additional, Szymanska, Maja, additional, Tanna, Angelo P., additional, Tanuj, Dada, additional, Tapply, Ian H., additional, Tatham, Andrew J., additional, Toris, Carol B., additional, Tsasousis, Konstantinos T., additional, Wang, Ningli, additional, Weinreb, Robert N., additional, Wiggs, Janey L., additional, Wo, Yu Jun, additional, Wollstein, Gadi, additional, Wu, Shen, additional, Wu, Zhichao, additional, Xin, Chen, additional, Yoo, Chungkwon, additional, Young, Cara Capitena, additional, and Zhang, Jingxue, additional

Published
2023
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27. Association of Systemic Medication Use with Glaucoma and Intraocular Pressure: The European Eye Epidemiology Consortium

Author

Vergroesen, Joëlle E., Schuster, Alexander K., Stuart, Kelsey V., Asefa, Nigus G., Cougnard-Grégoire, Audrey, Delcourt, Cécile, Schweitzer, Cédric, Barreto, Patrícia, Coimbra, Rita, Foster, Paul J., Luben, Robert N., Pfeiffer, Norbert, Stingl, Julia V., Kirsten, Toralf, Rauscher, Franziska G., Wirkner, Kerstin, Jansonius, Nomdo M., Arnould, Louis, Creuzot-Garcher, Catherine P., Stricker, Bruno H., Keskini, Christina, Topouzis, Fotis, Bertelsen, Geir, Eggen, Anne E., Bikbov, Mukharram M., Jonas, Jost B., Klaver, Caroline C.W., Ramdas, Wishal D., and Khawaja, Anthony P.

Published
2023
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29. The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population

Author

Stuart, Kelsey V., primary, Biradar, Mahantesh I., additional, Luben, Robert N., additional, Dhaun, Neeraj, additional, Wagner, Siegfried K., additional, Warwick, Alasdair N., additional, Sun, Zihan, additional, Madjedi, Kian M., additional, Pasquale, Louis R., additional, Wiggs, Janey L., additional, Kang, Jae H., additional, Lentjes, Marleen A.H., additional, Aschard, Hugues, additional, Kim, Jihye, additional, Foster, Paul J., additional, Khawaja, Anthony P., additional, Chia, Mark, additional, Chua, Sharon, additional, Do, Ron, additional, Foster, Paul, additional, Kang, Jae, additional, Kastner, Alan, additional, Khawaja, Anthony, additional, Lentjes, Marleen, additional, Luben, Robert, additional, Madjedi, Kian, additional, Montesano, Giovanni, additional, Pasquale, Louis, additional, Stuart, Kelsey, additional, Warwick, Alasdair, additional, Wiggs, Janey, additional, Allen, Naomi, additional, Aslam, Tariq, additional, Atan, Denize, additional, Barman, Sarah, additional, Barrett, Jenny, additional, Bishop, Paul, additional, Black, Graeme, additional, Braithwaite, Tasanee, additional, Carare, Roxana, additional, Chakravarthy, Usha, additional, Chan, Michelle, additional, Day, Alexander, additional, Desai, Parul, additional, Dhillon, Bal, additional, Dick, Andrew, additional, Doney, Alexander, additional, Egan, Cathy, additional, Ennis, Sarah, additional, Fruttiger, Marcus, additional, Garway-Heath, David (Ted), additional, Gibson, Jane, additional, Guggenheim, Jeremy, additional, Hammond, Chris, additional, Hardcastle, Alison, additional, Harding, Simon, additional, Hogg, Ruth, additional, Hysi, Pirro, additional, Keane, Pearse, additional, Khaw, Peng Tee, additional, Lascaratos, Gerassimos, additional, Littlejohns, Thomas, additional, Lotery, Andrew, additional, Luthert, Phil, additional, MacGillivray, Tom, additional, Mackie, Sarah, additional, McGuinness, Bernadette, additional, McKay, Gareth, additional, McKibbin, Martin, additional, Moore, Tony, additional, Morgan, James, additional, O'Sullivan, Eoin, additional, Oram, Richard, additional, Owen, Chris, additional, Patel, Praveen, additional, Paterson, Euan, additional, Peto, Tunde, additional, Petzold, Axel, additional, Pontikos, Nikolas, additional, Rahi, Jugnoo, additional, Rudnicka, Alicja, additional, Sattar, Naveed, additional, Self, Jay, additional, Sergouniotis, Panagiotis, additional, Sivaprasad, Sobha, additional, Steel, David, additional, Stratton, Irene, additional, Strouthidis, Nicholas, additional, Sudlow, Cathie, additional, Tapp, Robyn, additional, Thomas, Dhanes, additional, Trucco, Emanuele, additional, Tufail, Adnan, additional, Viswanathan, Ananth, additional, Vitart, Veronique, additional, Weedon, Mike, additional, Williams, Katie, additional, Williams, Cathy, additional, Woodside, Jayne, additional, Yates, Max, additional, Yip, Jennifer, additional, Zheng, Yalin, additional, Aung, Tin, additional, Burdon, Kathryn, additional, Chen, Li, additional, Cheng, Ching-Yu, additional, Craig, Jamie, additional, Cree, Angela, additional, de Vries, Victor, additional, Driessen, Sjoerd, additional, Fingert, John, additional, Gharahkhani, Puya, additional, Hammond, Christopher, additional, Hayward, Caroline, additional, Hewitt, Alex, additional, Jansonius, Nomdo, additional, Jonansson, Fridbert, additional, Jonas, Jost, additional, Kass, Michael, additional, Khor, Chiea, additional, Klaver, Caroline, additional, Koh, Jacyline, additional, MacGregor, Stuart, additional, Mackey, David, additional, Mitchell, Paul, additional, Pang, Calvin, additional, Pasutto, Francesca, additional, Pfeiffer, Norbert, additional, Polašek, Ozren, additional, Ramdas, Wishal, additional, Schuster, Alexander, additional, Segrè, Ayellet, additional, Stefansson, Einer, additional, Stefánsson, Kári, additional, Thorleifsson, Gudmar, additional, Thorsteinsdottir, Unnur, additional, van Duijn, Cornelia, additional, Vergroesen, Joëlle, additional, Vithana, Eranga, additional, Wilson, James, additional, Wojciechowski, Robert, additional, Wong, Tien, additional, and Young, Terri, additional

Published
2024
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31. Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

Author

Iglesias, Adriana I, Mishra, Aniket, Vitart, Veronique, Bykhovskaya, Yelena, Höhn, René, Springelkamp, Henriët, Cuellar-Partida, Gabriel, Gharahkhani, Puya, Bailey, Jessica N Cooke, Willoughby, Colin E, Li, Xiaohui, Yazar, Seyhan, Nag, Abhishek, Khawaja, Anthony P, Polašek, Ozren, Siscovick, David, Mitchell, Paul, Tham, Yih Chung, Haines, Jonathan L, Kearns, Lisa S, Hayward, Caroline, Shi, Yuan, van Leeuwen, Elisabeth M, Taylor, Kent D, Blue Mountains Eye Study - GWAS group, Bonnemaijer, Pieter, Rotter, Jerome I, Martin, Nicholas G, Zeller, Tanja, Mills, Richard A, Souzeau, Emmanuelle, Staffieri, Sandra E, Jonas, Jost B, Schmidtmann, Irene, Boutin, Thibaud, Kang, Jae H, Lucas, Sionne EM, Wong, Tien Yin, Beutel, Manfred E, Wilson, James F, Wellcome Trust Case Control Consortium 2 (WTCCC2), NEIGHBORHOOD consortium, Uitterlinden, André G, Vithana, Eranga N, Foster, Paul J, Hysi, Pirro G, Hewitt, Alex W, Khor, Chiea Chuen, Pasquale, Louis R, Montgomery, Grant W, Klaver, Caroline CW, Aung, Tin, Pfeiffer, Norbert, Mackey, David A, Hammond, Christopher J, Cheng, Ching-Yu, Craig, Jamie E, Rabinowitz, Yaron S, Wiggs, Janey L, Burdon, Kathryn P, van Duijn, Cornelia M, and MacGregor, Stuart

Subjects
Blue Mountains Eye Study - GWAS group, Wellcome Trust Case Control Consortium 2, NEIGHBORHOOD consortium, Eye Disease and Disorders of Vision
Abstract

Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article.

Published
2019

32. Ascorbic acid metabolites are involved in intraocular pressure control in the general population.

Author

Hysi, Pirro G, Khawaja, Anthony P, Menni, Cristina, Tamraz, Bani, Wareham, Nick, Khaw, Kay-Tee, Foster, Paul J, Benet, Leslie Z, Spector, Tim D, and Hammond, Chris J

Subjects
Humans, Glaucoma, Ascorbic Acid, Intraocular Pressure, Adult, Aged, Middle Aged, Female, Male, Metabolomics, Metabolome, Public Health Surveillance, Ascorbate metabolism, Intraocular pressure, Multi-omics, Neurodegenerative, Prevention, Aging, Eye Disease and Disorders of Vision, Neurosciences, Multi-omits, Biochemistry and Cell Biology, Medical Biochemistry and Metabolomics, Pharmacology and Pharmaceutical Sciences
Abstract

Elevated intraocular pressure (IOP) is an important risk factor for glaucoma. Mechanisms involved in its homeostasis are not well understood, but associations between metabolic factors and IOP have been reported. To investigate the relationship between levels of circulating metabolites and IOP, we performed a metabolome-wide association using a machine learning algorithm, and then employing Mendelian Randomization models to further explore the strength and directionality of effect of the metabolites on IOP. We show that O-methylascorbate, a circulating Vitamin C metabolite, has a significant IOP-lowering effect, consistent with previous knowledge of the anti-hypertensive and anti-oxidative role of ascorbate compounds. These results enhance understanding of IOP control and may potentially benefit future IOP treatment and reduce vision loss from glaucoma.

Published
2019

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

Author

Iglesias, Adriana I, Mishra, Aniket, Vitart, Veronique, Bykhovskaya, Yelena, Höhn, René, Springelkamp, Henriët, Cuellar-Partida, Gabriel, Gharahkhani, Puya, Bailey, Jessica N Cooke, Willoughby, Colin E, Li, Xiaohui, Yazar, Seyhan, Nag, Abhishek, Khawaja, Anthony P, Polašek, Ozren, Siscovick, David, Mitchell, Paul, Tham, Yih Chung, Haines, Jonathan L, Kearns, Lisa S, Hayward, Caroline, Shi, Yuan, van Leeuwen, Elisabeth M, Taylor, Kent D, Blue Mountains Eye Study—GWAS group, Bonnemaijer, Pieter, Rotter, Jerome I, Martin, Nicholas G, Zeller, Tanja, Mills, Richard A, Souzeau, Emmanuelle, Staffieri, Sandra E, Jonas, Jost B, Schmidtmann, Irene, Boutin, Thibaud, Kang, Jae H, Lucas, Sionne EM, Wong, Tien Yin, Beutel, Manfred E, Wilson, James F, NEIGHBORHOOD Consortium, Wellcome Trust Case Control Consortium 2 (WTCCC2), Uitterlinden, André G, Vithana, Eranga N, Foster, Paul J, Hysi, Pirro G, Hewitt, Alex W, Khor, Chiea Chuen, Pasquale, Louis R, Montgomery, Grant W, Klaver, Caroline CW, Aung, Tin, Pfeiffer, Norbert, Mackey, David A, Hammond, Christopher J, Cheng, Ching-Yu, Craig, Jamie E, Rabinowitz, Yaron S, Wiggs, Janey L, Burdon, Kathryn P, van Duijn, Cornelia M, and MacGregor, Stuart

Subjects
Blue Mountains Eye Study—GWAS group, NEIGHBORHOOD Consortium, Wellcome Trust Case Control Consortium 2, Cornea, Humans, Marfan Syndrome, Corneal Diseases, Corneal Dystrophies, Hereditary, Keratoconus, Eye Diseases, Hereditary, Glaucoma, Open-Angle, Myopia, Ehlers-Danlos Syndrome, Proteoglycans, Gene Expression, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genome, Human, Asian Continental Ancestry Group, European Continental Ancestry Group, Transforming Growth Factor beta2, Genome-Wide Association Study, Loeys-Dietz Syndrome, Mendelian Randomization Analysis, Decorin, Lumican, Fibrillin-1, ADAMTS Proteins, Corneal Dystrophies, Hereditary, Eye Diseases, Glaucoma, Open-Angle, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, Genome, Human
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

37. Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma: a multi-cohort analysis

Author

Aschard, Hugues, Kang, Jae H, Iglesias, Adriana I, Hysi, Pirro, Cooke Bailey, Jessica N, Khawaja, Anthony P, Allingham, R Rand, Ashley-Koch, Allison, Lee, Richard K, Moroi, Sayoko E, Brilliant, Murray H, Wollstein, Gadi, Schuman, Joel S, Fingert, John H, Budenz, Donald L, Realini, Tony, Gaasterland, Terry, Scott, William K, Singh, Kuldev, Sit, Arthur J, Igo Jr, Robert P, Song, Yeunjoo E, Hark, Lisa, Ritch, Robert, Rhee, Douglas J, Gulati, Vikas, Haven, Shane, Vollrath, Douglas, Zack, Donald J, Medeiros, Felipe, Weinreb, Robert N, Cheng, Ching-Yu, Chasman, Daniel I, Christen, William G, Pericak-Vance, Margaret A, Liu, Yutao, Kraft, Peter, Richards, Julia E, Rosner, Bernard A, Hauser, Michael A, Klaver, Caroline CW, vanDuijn, Cornelia M, Haines, Jonathan, Wiggs, Janey L, and Pasquale, Louis R

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Ophthalmology and Optometry, Eye Disease and Disorders of Vision, Human Genome, Aging, Neurodegenerative, Neurosciences, Blood Pressure, Female, Genetic Predisposition to Disease, Glaucoma, Open-Angle, Humans, Intraocular Pressure, Linkage Disequilibrium, Male, International Glaucoma Genetics Consortium, Clinical Sciences, Genetics & Heredity, Clinical sciences
Abstract

Primary open-angle glaucoma (POAG) is the most common chronic optic neuropathy worldwide. Epidemiological studies show a robust positive relation between intraocular pressure (IOP) and POAG and modest positive association between IOP and blood pressure (BP), while the relation between BP and POAG is controversial. The International Glaucoma Genetics Consortium (n=27 558), the International Consortium on Blood Pressure (n=69 395), and the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (n=37 333), represent genome-wide data sets for IOP, BP traits and POAG, respectively. We formed genome-wide significant variant panels for IOP and diastolic BP and found a strong relation with POAG (odds ratio and 95% confidence interval: 1.18 (1.14-1.21), P=1.8 × 10-27) for the former trait but no association for the latter (P=0.93). Next, we used linkage disequilibrium (LD) score regression, to provide genome-wide estimates of correlation between traits without the need for additional phenotyping. We also compared our genome-wide estimate of heritability between IOP and BP to an estimate based solely on direct measures of these traits in the Erasmus Rucphen Family (ERF; n=2519) study using Sequential Oligogenic Linkage Analysis Routines (SOLAR). LD score regression revealed high genetic correlation between IOP and POAG (48.5%, P=2.1 × 10-5); however, genetic correlation between IOP and diastolic BP (P=0.86) and between diastolic BP and POAG (P=0.42) were negligible. Using SOLAR in the ERF study, we confirmed the minimal heritability between IOP and diastolic BP (P=0.63). Overall, IOP shares genetic basis with POAG, whereas BP has limited shared genetic correlation with IOP or POAG.

Published
2017

38. A predictive atlas of disease onset from retinal fundus photographs

Author

Buergel, Thore, primary, Loock, Lukas, additional, Steinfeldt, Jakob, additional, Hoffmann, Laura, additional, Kuenzel, Steffen Emil, additional, Upmeier zu Belzen, Julius, additional, Khawaja, Anthony P., additional, Luben, Robert, additional, Foster, Paul J., additional, Langenberg, Claudia, additional, Landmesser, Ulf, additional, Deanfield, John, additional, Zeitz, Oliver, additional, Joussen, Antonia, additional, Pietzner, Maik, additional, Wild, Benjamin, additional, and Eils, Roland, additional

Published
2024
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39. OP-09 Structural correlations between brain magnetic resonance image-derived phenotypes and retinal neuroanatomy

Author

Sun, Zihan, primary, Zhang, Bing, additional, Smith, Stephen, additional, Atan, Denize, additional, Khawaja, Anthony P, additional, Stuart, Kelsey V, additional, Luben, Robert N, additional, Biradar, Mahantesh I, additional, McGillivray, Thomas, additional, Patel, Praveen J, additional, Khaw, Peng T, additional, Petzold, Axel, additional, and Foster, Paul J, additional

Published
2024
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40. The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population

Author

Stuart, Kelsey V., Biradar, Mahantesh I., Luben, Robert N., Dhaun, Neeraj, Wagner, Siegfried K., Warwick, Alasdair N., Sun, Zihan, Madjedi, Kian M., Pasquale, Louis R., Wiggs, Janey L., Kang, Jae H., Lentjes, Marleen, Aschard, Hugues, Kim, Jihye, Foster, Paul J., Khawaja, Anthony P., Stuart, Kelsey V., Biradar, Mahantesh I., Luben, Robert N., Dhaun, Neeraj, Wagner, Siegfried K., Warwick, Alasdair N., Sun, Zihan, Madjedi, Kian M., Pasquale, Louis R., Wiggs, Janey L., Kang, Jae H., Lentjes, Marleen, Aschard, Hugues, Kim, Jihye, Foster, Paul J., and Khawaja, Anthony P.

Abstract

OBJECTIVE: Excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may influence intraocular pressure (IOP) and glaucoma risk. This study aimed to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits, and to determine whether this relationship is modified by genetic susceptibility to disease. DESIGN: Cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study. PARTICIPANTS: Up to 103 634 individuals (mean age 57 years, 51% women) with complete urinary, ocular, and covariable data. METHODS: Urine sodium:creatinine ratio (UNa:Cr; mmol:mmol) was calculated from a midstream urine sample. Ocular parameters were measured as part of a comprehensive eye examination and glaucoma case ascertainment was through a combination of self-report and linked national hospital records. Genetic susceptibility to glaucoma was calculated based on a glaucoma polygenic risk score (PRS) comprising 2 673 common genetic variants. Multivariable linear and logistic regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to model associations and gene-environment interactions. MAIN OUTCOME MEASURES: Corneal-compensated IOP, optical coherence tomography derived macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness, and prevalent glaucoma. RESULTS: In maximally adjusted regression models, a one standard deviation increase in UNa:Cr was associated with higher IOP (0.14mmHg; 95% CI, 0.12 to 0.17; P<0.001) and greater prevalence of glaucoma (OR, 1.11; 95% CI, 1.07 to 1.14; P<0.001), but not mRNFL or GCIPL thickness. Compared to those with UNa:Cr in the lowest quintile, those in the highest quintile had significantly higher IOP (0.45mmHg; 95% CI, 0.36 to 0.53, P<0.001) and prevalence of glaucoma (OR, 1.30; 95% CI, 1.17 t

Published
2024
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41. Structural correlations between brain magnetic resonance image‐derived phenotypes and retinal neuroanatomy.

Author

Sun, Zihan, Zhang, Bing, Smith, Stephen, Atan, Denize, Khawaja, Anthony P., Stuart, Kelsey V., Luben, Robert N., Biradar, Mahantesh I., McGillivray, Thomas, Patel, Praveen J., Khaw, Peng T., Petzold, Axel, and Foster, Paul J.

Subjects
NEUROANATOMY, MAGNETIC resonance, PHENOTYPES, OPTICAL coherence tomography, MAGNETIC resonance imaging
Abstract

Background and purpose: The eye is a well‐established model of brain structure and function, yet region‐specific structural correlations between the retina and the brain remain underexplored. Therefore, we aim to explore and describe the relationships between the retinal layer thicknesses and brain magnetic resonance image (MRI)‐derived phenotypes in UK Biobank. Methods: Participants with both quality‐controlled optical coherence tomography (OCT) and brain MRI were included in this study. Retinal sublayer thicknesses and total macular thickness were derived from OCT scans. Brain image‐derived phenotypes (IDPs) of 153 cortical and subcortical regions were processed from MRI scans. We utilized multivariable linear regression models to examine the association between retinal thickness and brain regional volumes. All analyses were corrected for multiple testing and adjusted for confounders. Results: Data from 6446 participants were included in this study. We identified significant associations between volumetric brain MRI measures of subregions in the occipital lobe (intracalcarine cortex), parietal lobe (postcentral gyrus), cerebellum (lobules VI, VIIb, VIIIa, VIIIb, and IX), and deep brain structures (thalamus, hippocampus, caudate, putamen, pallidum, and accumbens) and the thickness of the innermost retinal sublayers and total macular thickness (all p < 3.3 × 10−5). We did not observe statistically significant associations between brain IDPs and the thickness of the outer retinal sublayers. Conclusions: Thinner inner and total retinal thicknesses are associated with smaller volumes of specific brain regions. Notably, these relationships extend beyond anatomically established retina–brain connections. [ABSTRACT FROM AUTHOR]

Published
2024
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43. Differentiating glaucoma from chiasmal compression using optical coherence tomography: the macular naso-temporal ratio.

Author

Kleerekooper, Iris, Wagner, Siegfried K., Trip, S. Anand, Plant, Gordon T., Petzold, Axel, Keane, Pearse A., and Khawaja, Anthony P.

Abstract

Background/aims The analysis of visual field loss patterns is clinically useful to guide differential diagnosis of visual pathway pathology. This study investigates whether a novel index of macular atrophy patterns can discriminate between chiasmal compression and glaucoma. Methods A retrospective series of patients with preoperative chiasmal compression, primary open-angle glaucoma (POAG) and healthy controls. Macular optical coherence tomography (OCT) images were analysed for the macular ganglion cell and inner plexiform layer (mGCIPL) thickness. The nasal hemi-macula was compared with the temporal hemi-macula to derive the macular naso-temporal ratio (mNTR). Differences between groups and diagnostic accuracy were explored with multivariable linear regression and the area under the receiver operating characteristic curve (AUC). Results We included 111 individuals (31 with chiasmal compression, 30 with POAG and 50 healthy controls). Compared with healthy controls, the mNTR was significantly greater in POAG cases (ß=0.07, 95% CI 0.03 to 0.11, p=0.001) and lower in chiasmal compression cases (ß=-0.12, 95% CI -0.16 to -0.09, p<0.001), even though overall mGCIPL thickness did not discriminate between these pathologies (p=0.36). The mNTR distinguished POAG from chiasmal compression with an AUC of 95.3% (95% CI 90% to 100%). The AUCs when comparing healthy controls to POAG and chiasmal compression were 79.0% (95% CI 68% to 90%) and 89.0% (95% CI 80% to 98%), respectively. Conclusions The mNTR can distinguish between chiasmal compression and POAG with high discrimination. This ratio may provide utility over-and-above previously reported sectoral thinning metrics. Incorporation of mNTR into the output of OCT instruments may aid earlier diagnosis of chiasmal compression. [ABSTRACT FROM AUTHOR]

Published
2024
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44. Periodontitis and outer retinal thickness: A cross-sectional analysis of the UK Biobank cohort

Author

Wagner, Siegfried K., primary, Patel, Praveen J., additional, Huemer, Josef, additional, Khalid, Hagar, additional, Stuart, Kelsey V., additional, Chu, Colin J., additional, Williamson, Dominic J., additional, Struyven, Robbert R., additional, Romero-Bascones, David, additional, Foster, Paul J., additional, Khawaja, Anthony P., additional, Petzold, Axel, additional, Balaskas, Konstantinos, additional, Cortina-Borja, Mario, additional, Chapple, Iain, additional, Dietrich, Thomas, additional, Rahi, Jugnoo S., additional, Denniston, Alastair K., additional, Keane, Pearse A., additional, Allen, Naomi, additional, Aslam, Tariq, additional, Atan, Denize, additional, Balaskas, Konsantinos, additional, Barman, Sarah A., additional, Barrett, Jenny H., additional, Bishop, Paul, additional, Black, Graeme, additional, Braithwaite, Tasanee, additional, Carare, Roxana O., additional, Chakravarthy, Usha, additional, Chan, Michelle, additional, Chua, Sharon Y.L., additional, Day, Alexander, additional, Desai, Parul, additional, Dhillon, Bal, additional, Dick, Andrew D., additional, Doney, Alexander, additional, Egan, Cathy, additional, Ennis, Sarah, additional, Foster, Paul, additional, Fruttiger, Marcus, additional, Gallacher, John E.J., additional, Garway-Heath, David F., additional, Gibson, Jane, additional, Guggenheim, Jeremy A., additional, Hammond, Chris J., additional, Hardcastle, Alison, additional, Harding, Simon P., additional, Hogg, Ruth E., additional, Hysi, Pirro, additional, Khaw, Sir Peng T., additional, Lascaratos, Gerassimos, additional, Littlejohns, Thoams, additional, Lotery, Andrew J., additional, Luben, Robert, additional, Luthert, Phil, additional, Macgillivray, Tom, additional, Mackie, Sarah, additional, McGuinness, Bernadette, additional, McKay, Gareth J., additional, McKibbin, Martin, additional, Moore, Tony, additional, Morgan, James E., additional, O’Sullivan, Eoin, additional, Oram, Richard, additional, Owen, Chris G., additional, Patel, Praveen, additional, Paterson, Euan, additional, Peto, Tunde, additional, Rudnikca, Alicja R., additional, Sattar, Naveed, additional, Self, Jay, additional, Sergouniotis, Panagiotis, additional, Sivaprasad, Sobha, additional, Steel, David, additional, Stratton, Irene, additional, Strouthidis, Nicholas, additional, Sudlow, Cathie, additional, Sun, Zihan, additional, Tapp, Robyn, additional, Thomas, Dhanes, additional, Trucco, Emanuele, additional, Tufail, Adnan, additional, Vitart, Veronique, additional, Viswanathan, Ananth C., additional, Weedon, Mike, additional, Williams, Cathy, additional, Williams, Katie, additional, Woodside, Jayne V., additional, Yates, MaxM., additional, Yip, Jennifer, additional, and Zheng, Yalin, additional

Published
2024
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45. Assessing the Association of Mitochondrial Genetic Variation With Primary Open-Angle Glaucoma Using Gene-Set AnalysesMitochondrial Genetic Variation and POAG

Author

Khawaja, Anthony P, Bailey, Jessica N Cooke, Kang, Jae Hee, Allingham, R Rand, Hauser, Michael A, Brilliant, Murray, Budenz, Donald L, Christen, William G, Fingert, John, Gaasterland, Douglas, Gaasterland, Terry, Kraft, Peter, Lee, Richard K, Lichter, Paul R, Liu, Yutao, Medeiros, Felipe, Moroi, Syoko E, Richards, Julia E, Realini, Tony, Ritch, Robert, Schuman, Joel S, Scott, William K, Singh, Kuldev, Sit, Arthur J, Vollrath, Douglas, Wollstein, Gadi, Zack, Donald J, Zhang, Kang, Pericak-Vance, Margaret, Weinreb, Robert N, Haines, Jonathan L, Pasquale, Louis R, and Wiggs, Janey L

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Eye Disease and Disorders of Vision, Neurosciences, Neurodegenerative, Genetics, Aging, 2.1 Biological and endogenous factors, Aetiology, glaucoma, genetics, mitochondria, Biological Sciences, Medical and Health Sciences, Ophthalmology & Optometry, Ophthalmology and optometry
Abstract

PurposeRecent studies indicate that mitochondrial proteins may contribute to the pathogenesis of primary open-angle glaucoma (POAG). In this study, we examined the association between POAG and common variations in gene-encoding mitochondrial proteins.MethodsWe examined genetic data from 3430 POAG cases and 3108 controls derived from the combination of the GLAUGEN and NEIGHBOR studies. We constructed biological-system coherent mitochondrial nuclear-encoded protein gene-sets by intersecting the MitoCarta database with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We examined the mitochondrial gene-sets for association with POAG and with normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) subsets using Pathway Analysis by Randomization Incorporating Structure.ResultsWe identified 22 KEGG pathways with significant mitochondrial protein-encoding gene enrichment, belonging to six general biological classes. Among the pathway classes, mitochondrial lipid metabolism was associated with POAG overall (P = 0.013) and with NTG (P = 0.0006), and mitochondrial carbohydrate metabolism was associated with NTG (P = 0.030). Examining the individual KEGG pathway mitochondrial gene-sets, fatty acid elongation and synthesis and degradation of ketone bodies, both lipid metabolism pathways, were significantly associated with POAG (P = 0.005 and P = 0.002, respectively) and NTG (P = 0.0004 and P < 0.0001, respectively). Butanoate metabolism, a carbohydrate metabolism pathway, was significantly associated with POAG (P = 0.004), NTG (P = 0.001), and HTG (P = 0.010).ConclusionsWe present an effective approach for assessing the contributions of mitochondrial genetic variation to open-angle glaucoma. Our findings support a role for mitochondria in POAG pathogenesis and specifically point to lipid and carbohydrate metabolism pathways as being important.

Published
2016

46. Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma

Author

Bailey, Jessica N Cooke, Loomis, Stephanie J, Kang, Jae H, Allingham, R Rand, Gharahkhani, Puya, Khor, Chiea Chuen, Burdon, Kathryn P, Aschard, Hugues, Chasman, Daniel I, Igo, Robert P, Hysi, Pirro G, Glastonbury, Craig A, Ashley-Koch, Allison, Brilliant, Murray, Brown, Andrew A, Budenz, Donald L, Buil, Alfonso, Cheng, Ching-Yu, Choi, Hyon, Christen, William G, Curhan, Gary, De Vivo, Immaculata, Fingert, John H, Foster, Paul J, Fuchs, Charles, Gaasterland, Douglas, Gaasterland, Terry, Hewitt, Alex W, Hu, Frank, Hunter, David J, Khawaja, Anthony P, Lee, Richard K, Li, Zheng, Lichter, Paul R, Mackey, David A, McGuffin, Peter, Mitchell, Paul, Moroi, Sayoko E, Perera, Shamira A, Pepper, Keating W, Qi, Qibin, Realini, Tony, Richards, Julia E, Ridker, Paul M, Rimm, Eric, Ritch, Robert, Ritchie, Marylyn, Schuman, Joel S, Scott, William K, Singh, Kuldev, Sit, Arthur J, Song, Yeunjoo E, Tamimi, Rulla M, Topouzis, Fotis, Viswanathan, Ananth C, Verma, Shefali Setia, Vollrath, Douglas, Wang, Jie Jin, Weisschuh, Nicole, Wissinger, Bernd, Wollstein, Gadi, Wong, Tien Y, Yaspan, Brian L, Zack, Donald J, Zhang, Kang, Study, EPIC-Norfolk Eye, Weinreb, Robert N, Pericak-Vance, Margaret A, Small, Kerrin, Hammond, Christopher J, Aung, Tin, Liu, Yutao, Vithana, Eranga N, MacGregor, Stuart, Craig, Jamie E, Kraft, Peter, Howell, Gareth, Hauser, Michael A, Pasquale, Louis R, Haines, Jonathan L, and Wiggs, Janey L

Subjects
Biological Sciences, Genetics, Eye Disease and Disorders of Vision, Neurodegenerative, Neurosciences, Human Genome, Aging, Eye, Ataxin-2, Forkhead Transcription Factors, Genetic Predisposition to Disease, Genome-Wide Association Study, Glaucoma, Open-Angle, Humans, Polymorphism, Single Nucleotide, Thioredoxin Reductase 2, ANZRAG Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10(-11)) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10(-10)); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10(-10)). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.

Published
2016

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