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3. 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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4. 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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6. Associations between unilateral amblyopia in childhood and cardiometabolic disorders in adult life: a cross-sectional and longitudinal analysis of the UK Biobank

Author

Allen, Naomi, Aslam, Tariq, Atan, Denize, Balaskas, Konstantinos, Barman, Sarah, Barrett, Jenny, Bishop, Paul, Black, Graeme, Braithwaite, Tasanee, Carare, Roxana, Chakravarthy, Usha, Chan, Michelle, Chua, Sharon, Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew, Doney, Alexander, Egan, Cathy, Ennis, Sarah, Foster, Paul, Fruttiger, Marcus, Gallacher, John, Garway-heath, David (Ted), Gibson, Jane, Guggenheim, Jeremy, Hammond, Chris, Hardcastle, Alison, Harding, Simon, Hogg, Ruth, Hysi, Pirro, Keane, Pearse, Tee Khaw, Sir Peng, Khawaja, Anthony, Lascaratos, Gerassimos, Littlejohns, Thomas, Lotery, Andrew, Luben, Robert, Luthert, Phil, Macgillivray, Tom, Mackie, Sarah, Madhusudhan, Savita, 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, Zheng, Yalin, Thomas, Mervyn, Wagner, Siegfried Karl, Bountziouka, Vasiliki, and Rahi, Jugnoo Sangeeta

Published
2024
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7. 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

8. 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

9. 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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10. 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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11. 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

12. 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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13. Associations between unilateral amblyopia in childhood and cardiometabolic disorders in adult life: a cross-sectional and longitudinal analysis of the UK Biobank

Author

Wagner, Siegfried Karl, primary, Bountziouka, Vasiliki, additional, Hysi, Pirro, additional, Rahi, Jugnoo Sangeeta, additional, Allen, Naomi, additional, Aslam, Tariq, additional, Atan, Denize, additional, Balaskas, Konstantinos, 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, Chua, Sharon, additional, Day, Alexander, additional, Desai, Parul, additional, Dhillon, Bal, additional, Dick, Andrew, additional, Doney, Alexander, additional, Egan, Cathy, additional, Ennis, Sarah, additional, Foster, Paul, additional, Fruttiger, Marcus, additional, Gallacher, John, additional, Garway-heath, David (Ted), additional, Gibson, Jane, additional, Guggenheim, Jeremy, additional, Hammond, Chris, additional, Hardcastle, Alison, additional, Harding, Simon, additional, Hogg, Ruth, additional, Keane, Pearse, additional, Tee Khaw, Sir Peng, additional, Khawaja, Anthony, additional, Lascaratos, Gerassimos, additional, Littlejohns, Thomas, additional, Lotery, Andrew, additional, Luben, Robert, additional, Luthert, Phil, additional, Macgillivray, Tom, additional, Mackie, Sarah, additional, Madhusudhan, Savita, 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, Sun, Zihan, 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, Zheng, Yalin, additional, and Thomas, Mervyn, additional

Published
2024
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15. Glaucoma Patients Have a Lower Abundance of Butyrate-Producing Taxa in the Gut

Author

Vergroesen, Joëlle E, Jarrar, Zakariya A, Weiss, Stefan, Frost, Fabian, Ansari, Abdus S, Nguyen, Picard, Kraaij, Robert, Medina-Gomez, Carolina, Völzke, Henry, Tost, Frank, Amin, Najaf, van Duijn, Cornelia M, Klaver, Caroline C W, Jürgens, Clemens, Hammond, Chris J, Ramdas, Wishal D, Vergroesen, Joëlle E, Jarrar, Zakariya A, Weiss, Stefan, Frost, Fabian, Ansari, Abdus S, Nguyen, Picard, Kraaij, Robert, Medina-Gomez, Carolina, Völzke, Henry, Tost, Frank, Amin, Najaf, van Duijn, Cornelia M, Klaver, Caroline C W, Jürgens, Clemens, Hammond, Chris J, and Ramdas, Wishal D

Abstract

PURPOSE: Glaucoma is an eye disease that is the most common cause of irreversible blindness worldwide. It has been suggested that gut microbiota can produce reactive oxygen species and pro-inflammatory cytokines that may travel from the gastric mucosa to distal sites, for example, the optic nerve head or trabecular meshwork. There is evidence for a gut-eye axis, as microbial dysbiosis has been associated with retinal diseases. We investigated the microbial composition in patients with glaucoma and healthy controls. Moreover, we analyzed the association of the gut microbiome with intraocular pressure (IOP; risk factor of glaucoma) and vertical cup-to-disc ratio (VCDR; quantifying glaucoma severity).METHODS: The discovery analyses included participants of the Rotterdam Study and the Erasmus Glaucoma Cohort. A total of 225 patients with glaucoma and 1247 age- and sex-matched participants without glaucoma were included in our analyses. Stool samples were used to generate 16S rRNA gene profiles. We assessed associations with 233 genera and species. We used data from the TwinsUK and the Study of Health in Pomerania (SHIP) to replicate our findings.RESULTS: Several butyrate-producing taxa (e.g. Butyrivibrio, Caproiciproducens, Clostridium sensu stricto 1, Coprococcus 1, Ruminococcaceae UCG 007, and Shuttleworthia) were less abundant in people with glaucoma compared to healthy controls. The same taxa were also associated with lower IOP and smaller VCDR. The replication analyses confirmed the findings from the discovery analyses.CONCLUSIONS: Large human studies exploring the link between the gut microbiome and glaucoma are lacking. Our results suggest that microbial dysbiosis plays a role in the pathophysiology of glaucoma.

Published
2024

16. Glaucoma Patients Have a Lower Abundance of Butyrate-Producing Taxa in the Gut

Author

Vergroesen, Joëlle E., primary, Jarrar, Zakariya A., additional, Weiss, Stefan, additional, Frost, Fabian, additional, Ansari, Abdus S., additional, Nguyen, Picard, additional, Kraaij, Robert, additional, Medina-Gomez, Carolina, additional, Völzke, Henry, additional, Tost, Frank, additional, Amin, Najaf, additional, van Duijn, Cornelia M., additional, Klaver, Caroline C. W., additional, Jürgens, Clemens, additional, Hammond, Chris J., additional, and Ramdas, Wishal D., additional

Published
2024
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17. 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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18. A higher abundance of butyrate‐producing taxa in the gut is associated with lower glaucoma prevalence

Author

Vergroesen, Joëlle, primary, Jarrar, Zakariya, additional, Weiss, Stefan, additional, Frost, Fabian, additional, Kraaij, Robert, additional, Medina‐Gomez, Carolina, additional, Amin, Najaf, additional, van Duijn, Cornelia, additional, Klaver, Caroline, additional, Jürgens, Clemens, additional, Hammond, Chris, additional, and Ramdas, Wishal, additional

Published
2024
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19. Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci.

Author

Simpson, Claire L, Wojciechowski, Robert, Oexle, Konrad, Murgia, Federico, Portas, Laura, Li, Xiaohui, Verhoeven, Virginie JM, Vitart, Veronique, Schache, Maria, Hosseini, S Mohsen, Hysi, Pirro G, Raffel, Leslie J, Cotch, Mary Frances, Chew, Emily, Klein, Barbara EK, Klein, Ronald, Wong, Tien Yin, van Duijn, Cornelia M, Mitchell, Paul, Saw, Seang Mei, Fossarello, Maurizio, Wang, Jie Jin, DCCT/EDIC Research Group, Polašek, Ozren, Campbell, Harry, Rudan, Igor, Oostra, Ben A, Uitterlinden, André G, Hofman, Albert, Rivadeneira, Fernando, Amin, Najaf, Karssen, Lennart C, Vingerling, Johannes R, Döring, Angela, Bettecken, Thomas, Bencic, Goran, Gieger, Christian, Wichmann, H-Erich, Wilson, James F, Venturini, Cristina, Fleck, Brian, Cumberland, Phillippa M, Rahi, Jugnoo S, Hammond, Chris J, Hayward, Caroline, Wright, Alan F, Paterson, Andrew D, Baird, Paul N, Klaver, Caroline CW, Rotter, Jerome I, Pirastu, Mario, Meitinger, Thomas, Bailey-Wilson, Joan E, and Stambolian, Dwight

Subjects
DCCT/EDIC Research Group, Eye, Humans, Hyperopia, Myopia, Genetic Predisposition to Disease, Genetic Markers, Age of Onset, Linkage Disequilibrium, Phenotype, Polymorphism, Single Nucleotide, Alleles, Adult, Aged, Aged, 80 and over, Middle Aged, European Continental Ancestry Group, Female, Male, Genetic Association Studies, and over, Polymorphism, Single Nucleotide, General Science & Technology
Abstract

Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10(-8)), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10(-11)) and 8q12 (minimum p value 1.82×10(-11)) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. "Replication-level" association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.

Published
2014

21. Book Notes

Author

Saviotti, Pier Paolo, Reisman, D. A., Heertje, A., Steele, G. R., Watson, Katherine, Gerrard, Bill, Taylor, Robert, Binmore, Ken, Chambers, Marcus J., Koop, Gary, Cubitt, Robin, Pearce, David, Geroski, Paul, Hammond, Chris, Bailey, R. E., Marcus, Edward, Ietto-Gillies, Grazia, Begg, Iain, Cox, Howard, Ghosh, Dipak, Backhouse, Roger E., Wakelin, Katherine, Marcus, Edward, Sneessens, Henri, Gowland, David, Chawluk, Antoni, Ghadha, Jagjit, Gowland, David H., Davidson, Ian, Trautwein, Hans-Michael, Sosvilla-Rivero, Simon, Piggins, Ashley, Donald, David, Tait, Alan A., Mair, Douglas, Grahl, John, Gravelle, Hugh, Clarke, Roger, Hartley, Keith, Whitelegg, Drew, Cain, Peter, Morgan, Wyn, Walsh, Berndan, REad, Robert, Wakeley, Tim, Metcalfe, J. S., Alence, Rod, Hunter, Hanet, Liu, minquan, Rebick, Marcus E., Takalo, Tuomas, Ingham, Barbara, Redmond, John, Gekker, Ruvin, Myant, Martin, Hölscher, Jens, Blackhurst, Richard, and Munro, Alistair

Published
1998

22. Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma

Author

Khawaja, Anthony P., Cooke Bailey, Jessica N., Wareham, Nicholas J., Scott, Robert A., Simcoe, Mark, Igo, Jr, Robert P., Song, Yeunjoo E., Wojciechowski, Robert, Cheng, Ching-Yu, Khaw, Peng T., Pasquale, Louis R., Haines, Jonathan L., Foster, Paul J., Wiggs, Janey L., Hammond, Chris J., Hysi, Pirro G., UK Biobank Eye and Vision Consortium, and NEIGHBORHOOD Consortium

Published
2018
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23. Abstract CT190: Oncolytic virus TG6002 safety and activity after intrahepatic artery administration in patients with liver-dominant metastatic colorectal cancer

Author

Samson, Adel, primary, Smolenschi, Cristina, additional, Cassier, Philippe, additional, Patel, Jai V., additional, Hammond, Chris, additional, Kurzawa, Marta, additional, Sainte-Croix, Sophie, additional, West, Emma, additional, Sadoun, Alain, additional, and Bendjama, Kaidre, additional

Published
2023
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24. 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

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

Published
2023
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25. The Association of Alcohol Consumption with Glaucoma and Related Traits

Author

Stuart, Kelsey V., primary, Luben, Robert N., additional, Warwick, Alasdair N., additional, Madjedi, Kian M., additional, Patel, Praveen J., additional, Biradar, Mahantesh I., additional, Sun, Zihan, additional, Chia, Mark A., additional, Pasquale, Louis R., additional, Wiggs, Janey L., additional, Kang, Jae H., additional, Kim, Jihye, additional, Aschard, Hugues, additional, Tran, Jessica H., additional, Lentjes, Marleen A.H., 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, Gallacher, John, 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
2022
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26. Association analyses of rare variants identify two genes associated with refractive error

Author

Patasova, Karina, Haarman, Annechien E. G., Musolf, Anthony M., Mahroo, Omar A., Rahi, Jugnoo S., Falchi, Mario, Verhoeven, Virginie J. M., Bailey-Wilson, Joan E., Klaver, Caroline C. W., Duggal, Priya, Klein, Alison, Guggenheim, Jeremy A., Hammond, Chris J., Hysi, Pirro G., the CREAM Consortium, the UK Biobank Eye, Vision Consortium, Wang, Heming, Ophthalmology, Epidemiology, and Clinical Genetics

Subjects
Multidisciplinary, Gene Frequency, Humans, Genetic Predisposition to Disease, Refractive Errors, Polymorphism, Single Nucleotide, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Genome-Wide Association Study, Transcription Factors
Abstract

Purpose Genetic variants identified through population-based genome-wide studies are generally of high frequency, exerting their action in the central part of the refractive error spectrum. However, the power to identify associations with variants of lower minor allele frequency is greatly reduced, requiring considerable sample sizes. Here we aim to assess the impact of rare variants on genetic variation of refractive errors in a very large general population cohort. Methods Genetic association analyses of non-cyclopaedic autorefraction calculated as mean spherical equivalent (SPHE) used whole-exome sequence genotypic information from 50,893 unrelated participants in the UK Biobank of European ancestry. Gene-based analyses tested for association with SPHE using an optimised SNP-set kernel association test (SKAT-O) restricted to rare variants (minor allele frequency < 1%) within protein-coding regions of the genome. All models were adjusted for age, sex and common lead variants within the same locus reported by previous genome-wide association studies. Potentially causal markers driving association at significant loci were elucidated using sensitivity analyses by sequentially dropping the most associated variants from gene-based analyses. Results We found strong statistical evidence for association of SPHE with the SIX6 (p-value = 2.15 x 10−10, or Bonferroni-Corrected p = 4.41x10-06) and the CRX gene (p-value = 6.65 x 10−08, or Bonferroni-Corrected p = 0.001). The SIX6 gene codes for a transcription factor believed to be critical to the eye, retina and optic disc development and morphology, while CRX regulates photoreceptor specification and expression of over 700 genes in the retina. These novel associations suggest an important role of genes involved in eye morphogenesis in refractive error. Conclusion The results of our study support previous research highlighting the importance of rare variants to the genetic risk of refractive error. We explain some of the origins of the genetic signals seen in GWAS but also report for the first time a completely novel association with the CRX gene.

Published
2022

27. The Association between Serum Lipids and Intraocular Pressure in 2 Large United Kingdom Cohorts

Author

Madjedi, Kian M., primary, Stuart, Kelsey V., additional, Chua, Sharon Y.L., additional, Luben, Robert N., additional, Warwick, Alasdair, additional, Pasquale, Louis R., additional, Kang, Jae H., additional, Wiggs, Janey L., additional, Lentjes, Marleen A.H., additional, Aschard, Hugues, additional, Sattar, Naveed, additional, Foster, Paul J., additional, Khawaja, Anthony P., additional, Chia, Mark, additional, Do, Ron, additional, Kastner, Alan, additional, Kim, Jihye, additional, Montesano, Giovanni, additional, Atan, Denize, additional, Aslam, Tariq, additional, Barman, Sarah A., additional, Barrett, Jenny H., additional, Bishop, Paul, additional, Blows, Peter, additional, Bunce, Catey, additional, Carare, Roxana O., additional, Chakravarthy, Usha, additional, Chan, Michelle, additional, Crabb, David P., additional, Cumberland, Philippa M., additional, Day, Alexander, additional, Desai, Parul, additional, Dhillon, Bal, additional, Dick, Andrew D., 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, Gore, Dan, additional, Guggenheim, Jeremy A., additional, Hammond, Chris J., additional, Hardcastle, Alison, additional, Harding, Simon P., additional, Hogg, Ruth E., additional, Hysi, Pirro, additional, Keane, Pearse A., additional, Khaw, Sir Peng T., additional, Lascaratos, Gerassimos, additional, Lotery, Andrew J., additional, Macgillivray, Tom, additional, Mackie, Sarah, additional, Martin, Keith, additional, McGaughey, Michelle, additional, McGuinness, Bernadette, additional, McKay, Gareth J., additional, McKibbin, Martin, additional, Mitry, Danny, additional, Moore, Tony, additional, Morgan, James E., additional, Muthy, Zaynah A., additional, O’Sullivan, Eoin, additional, Owen, Chris G., additional, Patel, Praveen, additional, Paterson, Euan, additional, Peto, Tunde, additional, Petzold, Axel, additional, Rahi, Jugnoo S., additional, Rudnikca, Alicja R., additional, Self, Jay, additional, Sivaprasad, Sobha, additional, Steel, David, additional, Stratton, Irene, additional, Strouthidis, Nicholas, additional, Sudlow, Cathie, additional, Thomas, Dhanes, additional, Trucco, Emanuele, additional, Tufail, Adnan, additional, Vitart, Veronique, additional, Vernon, Stephen A., additional, Viswanathan, Ananth C., additional, Williams, Cathy, additional, Williams, Katie, additional, Woodside, Jayne V., additional, Yates, MaxM., additional, Yip, Jennifer, additional, and Zheng, Yalin, additional

Published
2022
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29. Investigation of associations between retinal microvascular parameters and albuminuria in UK Biobank: a cross-sectional case-control study

Author

Paterson, Euan N., Cardwell, Chris, MacGillivray, Thomas J., Trucco, Emanuele, Doney, Alexander S., Foster, Paul, Maxwell, Alexander P., McKay, Gareth, Aslam, Tariq, Barman, Sarah, Barrett, Jenny, Bishop, Paul, Blows, Peter, Bunce, Catey, Carare, Roxana, Chakravarthy, Usha, Chan, Michelle, Chianca, Antonietta, Cipriani, Valentina, Crabb, David, Cumberland, Philippa, Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew, Egan, Cathy, Ennis, Sarah, Fruttiger, Marcus, Gallacher, John, Garway-Heath, David (Ted), Gibson, Jane, Gore, Dan, Guggenheim, Jeremy, Hammond, Chris, Hardcastle, Alison, Harding, Simon, Hogg, Ruth, Hysi, Pirro, Keane, Pearse A., Khaw, Sir Peng Tee, Khawaja, Anthony, Lascaratos, Gerassimos, Lotery, Andrew, Luthert, Phil, MacGillivray, Tom, Mackie, Sarah, Martin, Keith, Morgan, James, Self, Jay, Stratton, Irene, Ophthalmology, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Neuroinfection & -inflammation, McKay, Gareth J [0000-0001-8197-6280], and Apollo - University of Cambridge Repository

Subjects
Male, medicine.medical_specialty, 030204 cardiovascular system & hematology, Fundus (eye), lcsh:RC870-923, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Medicine, Albuminuria, Humans, Renal Insufficiency, Chronic, Aged, Biological Specimen Banks, business.industry, Case-control study, Retinal Vessels, Retinal, Odds ratio, Diabetic retinopathy, Organ Size, Middle Aged, medicine.disease, lcsh:Diseases of the genitourinary system. Urology, United Kingdom, Blood pressure, Cross-Sectional Studies, chemistry, Nephrology, Case-Control Studies, Microvessels, 030221 ophthalmology & optometry, Cardiology, Female, RE, medicine.symptom, business, Kidney disease, Research Article, RC
Abstract

Background Associations between microvascular variation and chronic kidney disease (CKD) have been reported previously. Non-invasive retinal fundus imaging enables evaluation of the microvascular network and may offer insight to systemic risk associated with CKD. Methods Retinal microvascular parameters (fractal dimension [FD] – a measure of the complexity of the vascular network, tortuosity, and retinal arteriolar and venular calibre) were quantified from macula-centred fundus images using the Vessel Assessment and Measurement Platform for Images of the REtina (VAMPIRE) version 3.1 (VAMPIRE group, Universities of Dundee and Edinburgh, Scotland) and assessed for associations with renal damage in a case-control study nested within the multi-centre UK Biobank cohort study. Participants were designated cases or controls based on urinary albumin to creatinine ratio (ACR) thresholds. Participants with ACR ≥ 3 mg/mmol (ACR stages A2-A3) were characterised as cases, and those with an ACR Results Lower FD (less extensive microvascular branching) was associated with a small increase in odds of albuminuria independent of blood pressure, diabetes and other potential confounding variables (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.03–1.34 for arterioles and OR 1.24, CI 1.05–1.47 for venules). Measures of tortuosity or retinal arteriolar and venular calibre were not significantly associated with ACR. Conclusions This study supports previously reported associations between retinal microvascular FD and other metabolic disturbances affecting the systemic vasculature. The association between retinal microvascular FD and albuminuria, independent of diabetes and blood pressure, may represent a useful indicator of systemic vascular damage associated with albuminuria.

Published
2021

30. Integrating Service and Academic Study: Faculty Motivation and Satisfaction in Michigan Higher Education.

Author

Hammond, Chris

Abstract

Reports on a survey questionnaire of 130 Michigan college faculty who incorporate service-learning into academic courses, focusing on faculty motivation, satisfaction, and the intersection of the two. Results indicate significant differences concerning faculty motivation for using service learning, but also commonalities with other findings concerning faculty motivation and satisfaction. Initial motivation to use service-learning and later satisfaction were correlated. (Author/MSE)

Published
1994

33. Clinical and molecular predictors of mortality in neurofibromatosis 2: a UK national analysis of 1192 patients

Author

Hexter, Adam, Jones, Adrian, Joe, Harry, Heap, Laura, Smith, Miriam J, Wallace, Andrew J, Halliday, Dorothy, Parry, Allyson, Taylor, Amy, Raymond, Lucy, Shaw, Adam, Afridi, Shazia, Obholzer, Rupert, Axon, Patrick, King, Andrew T, Friedman, Jan M, Evans, D Gareth R, Burnet, Neil, Donnelly, Neil, Durie-Gair, Juliette, English, Martin, Folland, Nicola, Foweraker, Karen, Harris, Fiona, Harris, Frances, Heney, David, Jeffries, Sarah, Jena, Raj, Knight, Richard, Lamb, Tamara, Macfarlane, Robert, Mannion, Richard, Nicholson, James, Price, Richard, Rands, Ella, Sanghera, Paul, Scoffings, Daniel, Tysome, James, Ferner, Rosalie E, Hammond, Chris, Lascelles, Karine, Nunn, Terry, Saeed, Shakeel, Swampillai, Angela, Thomson, Suki, Walsh, Daniel, Williams, Victoria, Wood, Sue, Anup, Raji, Duff, Chris, Evans, D Gareth, Freeman, Simon R, Howie, Emma, Huson, Susan M, Jarvis, Nicola, Kamaly-Asi, Ian, King, Andrew, Kellett, Mark, Kilday, John-Paul, Lloyd, Simon K, Malluci, Connor, Mawman, Deborah, McBain, Catherine, Mills, Sam, OʼDriscoll, Martin, Patel, Sonia, Perry, Mary, Rutherford, Scott A, Scott-Kitching, Vilka, Stivaros, Stavros M, Thomas, Owen, Vassallo, Grace, Ward, Charlotte L, Blesing, Claire, Cogswell, Lucy, Dalton, Louise, Dodridge, Caroline, Elston, John, Giele, Henk, Hanemann, C Oliver, Howard, Wendy, Johnson, David, Kerr, Richard, Laws, Avianna, Lee, James, Mace, Elle, May, Anne, Milford, Chris, Pretorius, Peter, Ramsden, James, Redman, Caroline, Warner, Nicola, and Wilson, Shaun

Published
2015
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35. Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation

Author

Legius, Eric, primary, Messiaen, Ludwine, additional, Wolkenstein, Pierre, additional, Pancza, Patrice, additional, Avery, Robert A., additional, Berman, Yemima, additional, Blakeley, Jaishri, additional, Babovic-Vuksanovic, Dusica, additional, Cunha, Karin Soares, additional, Ferner, Rosalie, additional, Fisher, Michael J., additional, Friedman, Jan M., additional, Gutmann, David H., additional, Kehrer-Sawatzki, Hildegard, additional, Korf, Bruce R., additional, Mautner, Victor-Felix, additional, Peltonen, Sirkku, additional, Rauen, Katherine A., additional, Riccardi, Vincent, additional, Schorry, Elizabeth, additional, Stemmer-Rachamimov, Anat, additional, Stevenson, David A., additional, Tadini, Gianluca, additional, Ullrich, Nicole J., additional, Viskochil, David, additional, Wimmer, Katharina, additional, Yohay, Kaleb, additional, Gomes, Alicia, additional, Jordan, Justin T., additional, Mautner, Victor, additional, Merker, Vanessa L., additional, Smith, Miriam J., additional, Stevenson, David, additional, Anten, Monique, additional, Aylsworth, Arthur, additional, Baralle, Diana, additional, Barbarot, Sebastien, additional, Barker, Fred, additional, Ben-Shachar, Shay, additional, Bergner, Amanda, additional, Bessis, Didier, additional, Blanco, Ignacio, additional, Cassiman, Catherine, additional, Ciavarelli, Patricia, additional, Clementi, Maurizio, additional, Frébourg, Thierry, additional, Giovannini, Marco, additional, Halliday, Dorothy, additional, Hammond, Chris, additional, Hanemann, C.O., additional, Hanson, Helen, additional, Heiberg, Arvid, additional, Joly, Pascal, additional, Kalamarides, Michel, additional, Karajannis, Matthias, additional, Kroshinsky, Daniela, additional, Larralde, Margarita, additional, Lázaro, Conxi, additional, Le, Lu, additional, Link, Michael, additional, Listernick, Robert, additional, MacCollin, Mia, additional, Mallucci, Conor, additional, Moertel, Christopher, additional, Mueller, Amy, additional, Ngeow, Joanne, additional, Oostenbrink, Rianne, additional, Packer, Roger, additional, Papi, Laura, additional, Parry, Allyson, additional, Peltonen, Juha, additional, Pichard, Dominique, additional, Poppe, Bruce, additional, Rezende, Nilton, additional, Rodrigues, Luiz Oswaldo, additional, Rosser, Tena, additional, Ruggieri, Martino, additional, Serra, Eduard, additional, Steinke-Lange, Verena, additional, Stivaros, Stavros Michael, additional, Taylor, Amy, additional, Toelen, Jaan, additional, Tonsgard, James, additional, Trevisson, Eva, additional, Upadhyaya, Meena, additional, Varan, Ali, additional, Wilson, Meredith, additional, Wu, Hao, additional, Zadeh, Gelareh, additional, Huson, Susan M., additional, Evans, D. Gareth, additional, and Plotkin, Scott R., additional

Published
2021
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36. Retinal asymmetry in multiple sclerosis

Author

Petzold, Axel, Chua, Sharon Y. L., Khawaja, Anthony P., Keane, Pearse A., Khaw, Peng T., Reisman, Charles, Dhillon, Baljean, Strouthidis, Nicholas G., Foster, Paul J., Patel, Praveen J., Atan, Denize, Aslam, Tariq, Barman, Sarah A., Barrett, Jenny H., Bishop, Paul, Bunce, Catey, Carare, Roxana O., Chakravarthy, Usha, Chan, Michelle, Crabb, David P., Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew D., Egan, Cathy, Ennis, Sarah, Fruttiger, Marcus, Gallacher, John E. J., Garway-Heath, David F., Gibson, Jane, Gore, Dan, Guggenheim, Jeremy A., Hammond, Chris J., Hardcastle, Alison, Harding, Simon P., Hogg, Ruth E., Hysi, Pirro, Khaw, Sir Peng T., Lascaratos, Gerassimos, Lotery, Andrew J., MacGillivray, Tom, MacKie, Sarah, McGaughey, Michelle, McGuinness, Bernadette, McKay, Gareth J., McKibbin, Martin, Moore, Tony, Morgan, James E., Muthy, Zaynah A., O'Sullivan, Eoin, Owen, Chris G., Patel, Praveen, Paterson, Euan, Peto, Tunde, Rahi, Jugnoo S., Rudnikca, Alicja R., Self, Jay, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Strouthidis, Nicholas, Sudlow, Cathie, Thomas, Dhanes, Trucco, Emanuele, Tufail, Adnan, Vitart, Veronique, Vernon, Stephen A., Viswanathan, Ananth C., Williams, Cathy, Williams, Katie, Woodside, Jayne V., Yates, Max M., Zheng, Yalin, Consortium, UK Biobank Eye and Vision, Gallacher, JE, Neurology, Ophthalmology, APH - Mental Health, APH - Methodology, and Amsterdam Neuroscience - Neuroinfection & -inflammation

Subjects
Male, genetic structures, Youden's J statistic, Optic neuritis, Imaging, chemistry.chemical_compound, 0302 clinical medicine, medicine.diagnostic_test, AcademicSubjects/SCI01870, imaging, Middle Aged, Biobank, Female, demyelination, Demyelination, Tomography, Optical Coherence, medicine.medical_specialty, Multiple Sclerosis, Clinical Neurology, Sensitivity and Specificity, Retina, Multiple sclerosis, 03 medical and health sciences, Optical coherence tomography, SDG 3 - Good Health and Well-being, Ophthalmology, medicine, Humans, optic neuritis, Research ethics, Community level, Neuromyelitis optica, Receiver operating characteristic, business.industry, biomarkers, Retinal, Original Articles, medicine.disease, Confidence interval, eye diseases, chemistry, North west, 030221 ophthalmology & optometry, Optometry, AcademicSubjects/MED00310, RE, Neurology (clinical), sense organs, business, 030217 neurology & neurosurgery, Biomarkers, RC
Abstract

In a large community-based study, Petzold et al. show that optical coherence tomography measures of retinal asymmetry have high diagnostic sensitivity for multiple sclerosis, particularly in younger individuals without relevant comorbidities. The technique should be considered in future revisions of diagnostic criteria., The diagnosis of multiple sclerosis is based on a combination of clinical and paraclinical tests. The potential contribution of retinal optical coherence tomography (OCT) has been recognized. We tested the feasibility of OCT measures of retinal asymmetry as a diagnostic test for multiple sclerosis at the community level. In this community-based study of 72 120 subjects, we examined the diagnostic potential of the inter-eye difference of inner retinal OCT data for multiple sclerosis using the UK Biobank data collected at 22 sites between 2007 and 2010. OCT reporting and quality control guidelines were followed. The inter-eye percentage difference (IEPD) and inter-eye absolute difference (IEAD) were calculated for the macular retinal nerve fibre layer (RNFL), ganglion cell inner plexiform layer (GCIPL) complex and ganglion cell complex. Area under the receiver operating characteristic curve (AUROC) comparisons were followed by univariate and multivariable comparisons accounting for a large range of diseases and co-morbidities. Cut-off levels were optimized by ROC and the Youden index. The prevalence of multiple sclerosis was 0.0023 [95% confidence interval (CI) 0.00229–0.00231]. Overall the discriminatory power of diagnosing multiple sclerosis with the IEPD AUROC curve (0.71, 95% CI 0.67–0.76) and IEAD (0.71, 95% CI 0.67–0.75) for the macular GCIPL complex were significantly higher if compared to the macular ganglion cell complex IEPD AUROC curve (0.64, 95% CI 0.59–0.69, P = 0.0017); IEAD AUROC curve (0.63, 95% CI 0.58–0.68, P 0.14) with narrow confidence intervals. In conclusion, the OCT macular GCIPL complex IEPD and IEAD may be considered as supportive measurements for multiple sclerosis diagnostic criteria in a young patient without relevant co-morbidity. The metric does not allow separation of multiple sclerosis from neuromyelitis optica. Retinal OCT imaging is accurate, rapid, non-invasive, widely available and may therefore help to reduce need for invasive and more costly procedures. To be viable, higher sensitivity and specificity levels are needed.

Published
2021

37. Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images

Author

Currant, Hannah, Hysi, Pirro, Fitzgerald, Tomas W., Gharahkhani, Puya, Bonnemaijer, Pieter W.M., Senabouth, Anne, Hewitt, Alex W., Atan, Denize, Aung, Tin, Charng, Jason, Choquet, Hélène, Craig, Jamie, Khaw, Peng T., Klaver, Caroline C.W., Kubo, Michiaki, Ong, Jue Sheng, Pasquale, Louis R., Reisman, Charles A., Daniszewski, Maciej, Powell, Joseph E., Pébay, Alice, Simcoe, Mark J., Thiadens, Alberta A.H.J., van Duijn, Cornelia M., Yazar, Seyhan, Jorgenson, Eric, MacGregor, Stuart, Hammond, Chris J., Mackey, David A., Wiggs, Janey L., Foster, Paul J., Patel, Praveen J., Birney, Ewan, Khawaja, Anthony P., Currant, Hannah, Hysi, Pirro, Fitzgerald, Tomas W., Gharahkhani, Puya, Bonnemaijer, Pieter W.M., Senabouth, Anne, Hewitt, Alex W., Atan, Denize, Aung, Tin, Charng, Jason, Choquet, Hélène, Craig, Jamie, Khaw, Peng T., Klaver, Caroline C.W., Kubo, Michiaki, Ong, Jue Sheng, Pasquale, Louis R., Reisman, Charles A., Daniszewski, Maciej, Powell, Joseph E., Pébay, Alice, Simcoe, Mark J., Thiadens, Alberta A.H.J., van Duijn, Cornelia M., Yazar, Seyhan, Jorgenson, Eric, MacGregor, Stuart, Hammond, Chris J., Mackey, David A., Wiggs, Janey L., Foster, Paul J., Patel, Praveen J., Birney, Ewan, and Khawaja, Anthony P.

Abstract

Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.

Published
2021

39. IRF4 variants have age-specific effects on nevus count and predispose to melanorha

Author

Duffy, David L., Iles, Mark M., Glass, Dan, Zhu, Gu, Barrett, Jennifer H., Hoiom, Veronica, Zhao, Zhen Z., Sturm, Richard A., Soranzo, Nicole, Hammond, Chris, Kvaskoff, Marina, Whiteman, David C., Mangino, Massimo, Hansson, Johan, Newton-Bishop, Julia A., Bataille, Veronique, Hayward, Nicholas K., Martin, Nicholas G., Bishop, D. Timothy, Spector, Timothy D., and Montgomery, Grant W.

Subjects
Melanoma -- Genetic aspects, Melanoma -- Demographic aspects, Population genetics -- Research, Sun exposure -- Health aspects, Teenagers -- Genetic aspects, Teenagers -- Physiological aspects, Youth -- Genetic aspects, Youth -- Physiological aspects, Biological sciences
Published
2010

41. Ambient Air Pollution Associations with Retinal Morphology in the UK Biobank

Author

Chua, Sharon Y.L., Khawaja, Anthony P., Dick, Andrew D., Morgan, James, Dhillon, Baljean, Lotery, Andrew J., Strouthidis, Nicholas G., Reisman, Charles, Peto, Tunde, Khaw, Peng T., Foster, Paul J., Patel, Praveen J., Littlejohns, Thomas, Allen, Naomi, Beli, Eleni, Atan, Denize, Aslam, Tariq, Barman, Sarah A., Barrett, Jenny H., Bishop, Paul, Bunce, Catey, Carare, Roxana O., Chakravarthy, Usha, Chan, Michelle, Crabb, David P., Day, Alexander, Desai, Parul, Dhillon, Bal, Egan, Cathy, Ennis, Sarah, Fruttiger, Marcus, Gallacher, John E.J., Garway-Heath, David F., Gibson, Jane, Gore, Dan, Guggenheim, Jeremy A., Hammond, Chris J., Hardcastle, Alison, Harding, Simon P., Hogg, Ruth E., Hysi, Pirro, Keane, Pearse A., Lascaratos, Gerassimos, Macgillivray, Tom, Mackie, Sarah, McGaughey, Michelle, McGuinness, Bernadette, McKay, Gareth J., McKibbin, Martin, Moore, Tony, Morgan, James E., Muthy, Zaynah A., O’Sullivan, Eoin, Owen, Chris G., Paterson, Euan, Petzold, Axel, Rahi, Jugnoo S., Rudnikca, Alicja R., Self, Jay, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Strouthidis, Nicholas, Sudlow, Cathie, Thomas, Dhanes, Trucco, Emanuele, Tufail, Adnan, Vitart, Veronique, Vernon, Stephen A., Viswanathan, Ananth C., Williams, Cathy, Williams, Katie, Woodside, Jayne V., Yates, Max M., and Zheng, Yalin

Subjects
Adult, Male, Retinal Ganglion Cells, medicine.medical_specialty, Retinal layers, air pollution, Air pollution, Nerve fiber layer, Glaucoma, Outer plexiform layer, Retinal Pigment Epithelium, Absorbance, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Nerve Fibers, Retinal Diseases, Ophthalmology, Surveys and Questionnaires, medicine, Humans, Outer nuclear layer, Aged, Biological Specimen Banks, Chemistry, Clinical and Epidemiologic Research, Retinal, retinal layers, Middle Aged, medicine.disease, GF, SDG 11 - Sustainable Cities and Communities, United Kingdom, medicine.anatomical_structure, Cross-Sectional Studies, OCT, Inner nuclear layer, 030221 ophthalmology & optometry, Female, Nitrogen Oxides, Particulate Matter, RE, sense organs, Layer (electronics), 030217 neurology & neurosurgery, Tomography, Optical Coherence, Photoreceptor Cells, Vertebrate
Abstract

PURPOSE. Because air pollution has been linked to glaucoma and AMD, we characterized the relationship between pollution and retinal structure. METHODS. We examined data from 51,710 UK Biobank participants aged 40 to 69 years old. Ambient air pollution measures included particulates and nitrogen oxides. SD-OCT imaging measured seven retinal layers: retinal nerve fiber layer, ganglion cell–inner plexiform layer, inner nuclear layer, outer plexiform layer + outer nuclear layer, photoreceptor inner segments, photoreceptor outer segments, and RPE. Multivariable regression was used to evaluate associations between pollutants (per interquartile range increase) and retinal thickness, adjusting for age, sex, race, Townsend deprivation index, body mass index, smoking status, and refractive error. RESULTS. Participants exposed to greater particulate matter with an aerodynamic diameter of CONCLUSIONS. Greater exposure to PM2.5, PM2.5 absorbance, and nitrogen oxides were all associated with apparently adverse retinal structural features.

Published
2020

42. Comparison of Associations with Different Macular Inner Retinal Thickness Parameters in a Large Cohort: The UK Biobank

Author

Khawaja, Anthony P., Chua, Sharon, Hysi, Pirro G., Georgoulas, Stelios, Currant, Hannah, Fitzgerald, Tomas W., Birney, Ewan, Ko, Fang, Yang, Qi, Reisman, Charles, Garway-Heath, David F., Hammond, Chris J., Khaw, Peng T., Foster, Paul J., Patel, Praveen J., Strouthidis, Nicholas, Neurology, Ophthalmology, APH - Mental Health, and APH - Methodology

Subjects
sense organs
Abstract

Purpose: To describe and compare associations with macular retinal nerve fiber layer (mRNFL), ganglion cell complex (GCC), and ganglion cell–inner plexiform layer (GCIPL) thicknesses in a large cohort. Design: Cross-sectional study. Participants: We included 42 044 participants in the UK Biobank. The mean age was 56 years. Methods: Spectral-domain OCT macular images were segmented and analyzed. Corneal-compensated intraocular pressure (IOPcc) was measured with the Ocular Response Analyzer (Reichert, Corp., Buffalo, NY). Multivariable linear regression was used to examine associations with mean mRNFL, GCC, and GCIPL thicknesses. Factors examined were age, sex, ethnicity, height, body mass index (BMI), smoking status, alcohol intake, Townsend deprivation index, education level, diabetes status, spherical equivalent, and IOPcc. Main Outcome Measures: Thicknesses of mRNFL, GCC, and GCIPL. Results: We identified several novel independent associations with thinner inner retinal thickness. Thinner inner retina was associated with alcohol intake (most significant for GCIPL: –0.46 μm for daily or almost daily intake compared with special occasion only or never [95% confidence interval (CI), 0.61–0.30]; P = 1.1×10–8), greater social deprivation (most significant for GCIPL: –0.28 μm for most deprived quartile compared with least deprived quartile [95% CI, –0.42 to –0.14]; P = 6.6×10–5), lower educational attainment (most significant for mRNFL: –0.36 μm for less than O level compared with degree level [95% CI, –0.45 to 0.26]; P = 2.3×10–14), and nonwhite ethnicity (most significant for mRNFL comparing blacks with whites: –1.65 μm [95% CI, –1.86 to –1.43]; P = 2.4×10–50). Corneal-compensated intraocular pressure was associated most significantly with GCIPL (–0.04 μm/mmHg [95% CI, –0.05 to –0.03]; P = 4.0×10–10) and was not associated significantly with mRNFL (0.00 μm/mmHg [95% CI, –0.01 to 0.01]; P = 0.77). The variables examined explained a greater proportion of the variance of GCIPL (11%) than GCC (6%) or mRNFL (7%). Conclusions: The novel associations we identified may be important to consider when using inner retinal parameters as a diagnostic tool. Associations generally were strongest with GCIPL, particularly for IOP. This suggests that GCIPL may be the superior inner retinal biomarker for macular pathophysiologic processes and especially for glaucoma.

Published
2020

43. Associations with photoreceptor thickness measures in the UK Biobank

Author

Chua, Sharon YL, Dhillon, Baljean, Aslam, Tariq, Balaskas, Konstantinos, Yang, Qi, Keane, Pearse A, Tufail, Adnan, Reisman, Charles, Foster, Paul J, Patel, Praveen J, Bishop, Paul, Barman, Sarah A, Barrett, Jenny H, Blows, Peter, Bunce, Catey, Carare, Roxana O, Chakravarthy, Usha, Chan, Michelle, Crabb, David P, Cumberland, Philippa M, Day, Alexander, Desai, Parul, Sudlow, Cathie, Dick, Andrew D, Egan, Cathy, Ennis, Sarah, Fruttiger, Marcus, Gallacher, John EJ, Garway-Heath, David F, Gibson, Jane, Gore, Dan, Guggenheim, Jeremy A, Hammond, Chris J, Hardcastle, Alison, Harding, Simon P, Hogg, Ruth E, Hysi, Pirro, Khaw, Sir Peng T, Khawaja, Anthony P, Lascaratos, Gerassimos, Lotery, Andrew J, Macgillivray, Tom, Mackie, Sarah, Martin, Keith, Mcgaughey, Michelle, Mcguinness, Bernadette, Mckay, Gareth J, Mckibbin, Martin, Mitry, Danny, Moore, Tony, Morgan, James E, Muthy, Zaynah A, O'Sullivan, Eoin, Owen, Chris G, Paterson, Euan, Peto, Tunde, Petzold, Axel, Rahi, Jugnoo S, Rudnicka, Alicja R, Self, Jay, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Strouthidis, Nicholas, Thaung, Caroline, Thomas, Dhanes, Trucco, Emanuele, Vitart, Veronique, Vernon, Stephen A, Viswanathan, Ananth C, Williams, Cathy, Williams, Katie, Woodside, Jayne V, Yates, Max M, Yip, Jennifer, Zheng, Yalin, Tapp, Robyn, Consortium, UK Biobank Eye Vision, Dhillon, Baljean [0000-0001-5993-0278], Foster, Paul J [0000-0002-4755-177X], Patel, Praveen J [0000-0001-8682-4067], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Male, Refractive error, Intraocular pressure, Visual acuity, genetic structures, Epidemiology, Visual Acuity, lcsh:Medicine, Retinal Pigment Epithelium, Cornea, chemistry.chemical_compound, 0302 clinical medicine, lcsh:Science, Biological Specimen Banks, Multidisciplinary, medicine.diagnostic_test, Age Factors, Middle Aged, medicine.anatomical_structure, Eye examination, Female, medicine.symptom, Tomography, Optical Coherence, Photoreceptor Cells, Vertebrate, Adult, medicine.medical_specialty, Article, 03 medical and health sciences, Sex Factors, Ophthalmology, medicine, Humans, General, Intraocular Pressure, Aged, Retinal pigment epithelium, business.industry, lcsh:R, Retinal, medicine.disease, United Kingdom, eye diseases, 030104 developmental biology, Blood pressure, chemistry, Risk factors, 030221 ophthalmology & optometry, RE, lcsh:Q, sense organs, business
Abstract

Funder: DH | NIHR | Health Services Research Programme (NIHR Health Services Research Programme); doi: https://doi.org/10.13039/501100001923, Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness.

Published
2019

44. Quantile regression analysis reveals widespread evidence for gene-environment or gene-gene interactions in myopia development

Author

Pozarickij, Alfred, Williams, Cathy, Hysi, Pirro G., Guggenheim, Jeremy A., Aslam, Tariq, Barman, Sarah A., Barrett, Jenny H., Bishop, Paul, Blows, Peter, Bunce, Catey, Carare, Roxana O., Chakravarthy, Usha, Chan, Michelle, Chua, Sharon Y.L., Crabb, David P., Cumberland, Philippa M., Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew D., Egan, Cathy, Ennis, Sarah, Foster, Paul, Fruttiger, Marcus, Gallacher, John E.J., Garway-Heath, David F., Gibson, Jane, Gore, Dan, Hammond, Chris J., Hardcastle, Alison, Harding, Simon P., Hogg, Ruth E., Keane, Pearse A., Khaw, Sir Peng T., Khawaja, Anthony P., Lascaratos, Gerassimos, Lotery, Andrew J., Mac Gillivray, Tom, Mackie, Sarah, Martin, Keith, McGaughey, Michelle, McGuinness, Bernadette, McKay, Gareth J., McKibbin, Martin, Mitry, Danny, Moore, Tony, Morgan, James E., Muthy, Zaynah A., O’Sullivan, Eoin, and Self, Jay

Abstract

A genetic contribution to refractive error has been confirmed by the discovery of more than 150 associated variants in genome-wide association studies (GWAS). Environmental factors such as education and time outdoors also demonstrate strong associations. Currently however, the extent of gene-environment or gene-gene interactions in myopia is unknown. We tested the hypothesis that refractive error-associated variants exhibit effect size heterogeneity, a hallmark feature of genetic interactions. Of 146 variants tested, evidence of non-uniform, non-linear effects were observed for 66 (45%) at Bonferroni-corrected significance (P < 1.1 × 10 −4) and 128 (88%) at nominal significance (P < 0.05). LAMA2 variant rs12193446, for example, had an effect size varying from −0.20 diopters (95% CI −0.18 to −0.23) to −0.89 diopters (95% CI −0.71 to −1.07) in different individuals. SNP effects were strongest at the phenotype extremes and weaker in emmetropes. A parsimonious explanation for these findings is that gene-environment or gene-gene interactions in myopia are pervasive.

Published
2019

45. Association Between Medication-Taking and Refractive Error in a Large General Population-Based Cohort

Author

Patasova, Karina, primary, Khawaja, Anthony P., additional, Tamraz, Bani, additional, Williams, Katie M., additional, Mahroo, Omar A., additional, Freidin, Maxim, additional, Solebo, Ameenat L., additional, Vehof, Jelle, additional, Falchi, Mario, additional, Rahi, Jugnoo S., additional, Hammond, Chris J., additional, and Hysi, Pirro G., additional

Published
2021
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47. New gene functions in megakaryopoiesis and platelet formation

Author

Gieger, Christian, Radhakrishnan, Aparna, Cvejic, Ana, Tang, Weihong, Porcu, Eleonora, Pistis, Giorgio, Serbanovic-Canic, Jovana, Elling, Ulrich, Goodall, Alison H., Labrune, Yann, Lopez, Lorna M., Mägi, Reedik, Meacham, Stuart, Okada, Yukinori, Pirastu, Nicola, Sorice, Rossella, Teumer, Alexander, Voss, Katrin, Zhang, Weihua, Ramirez-Solis, Ramiro, Bis, Joshua C., Ellinghaus, David, Gögele, Martin, Hottenga, Jouke-Jan, Langenberg, Claudia, Kovacs, Peter, O’Reilly, Paul F., Shin, So-Youn, Esko, Tõnu, Hartiala, Jaana, Kanoni, Stavroula, Murgia, Federico, Parsa, Afshin, Stephens, Jonathan, van der Harst, Pim, Ellen van der Schoot, C., Allayee, Hooman, Attwood, Antony, Balkau, Beverley, Bastardot, François, Basu, Saonli, Baumeister, Sebastian E., Biino, Ginevra, Bomba, Lorenzo, Bonnefond, Amélie, Cambien, François, Chambers, John C., Cucca, Francesco, D’Adamo, Pio, Davies, Gail, de Boer, Rudolf A., de Geus, Eco J. C., Döring, Angela, Elliott, Paul, Erdmann, Jeanette, Evans, David M., Falchi, Mario, Feng, Wei, Folsom, Aaron R., Frazer, Ian H., Gibson, Quince D., Glazer, Nicole L., Hammond, Chris, Hartikainen, Anna-Liisa, Heckbert, Susan R., Hengstenberg, Christian, Hersch, Micha, Illig, Thomas, Loos, Ruth J. F., Jolley, Jennifer, Tee Khaw, Kay, Kühnel, Brigitte, Kyrtsonis, Marie-Christine, Lagou, Vasiliki, Lloyd-Jones, Heather, Lumley, Thomas, Mangino, Massimo, Maschio, Andrea, Mateo Leach, Irene, McKnight, Barbara, Memari, Yasin, Mitchell, Braxton D., Montgomery, Grant W., Nakamura, Yusuke, Nauck, Matthias, Navis, Gerjan, Nöthlings, Ute, Nolte, Ilja M., Porteous, David J., Pouta, Anneli, Pramstaller, Peter P., Pullat, Janne, Ring, Susan M., Rotter, Jerome I., Ruggiero, Daniela, Ruokonen, Aimo, Sala, Cinzia, Samani, Nilesh J., Sambrook, Jennifer, Schlessinger, David, Schreiber, Stefan, Schunkert, Heribert, Scott, James, Smith, Nicholas L., Snieder, Harold, Starr, John M., Stumvoll, Michael, Takahashi, Atsushi, Tang, Wilson W.H., Taylor, Kent, Tenesa, Albert, Lay Thein, Swee, Tönjes, Anke, Uda, Manuela, Ulivi, Sheila, van Veldhuisen, Dirk J., Visscher, Peter M., Völker, Uwe, Wichmann, Erich H., Wiggins, Kerri L., Willemsen, Gonneke, Yang, Tsun-Po, Hua Zhao, Jing, Zitting, Paavo, Bradley, John R., Dedoussis, George V., Gasparini, Paolo, Hazen, Stanley L., Metspalu, Andres, Pirastu, Mario, Shuldiner, Alan R., Joost van Pelt, L., Zwaginga, Jaap-Jan, Boomsma, Dorret I., Deary, Ian J., Franke, Andre, Froguel, Philippe, Ganesh, Santhi K., Jarvelin, Marjo-Riitta, Martin, Nicholas G., Meisinger, Christa, Psaty, Bruce M., Spector, Timothy D., Wareham, Nicholas J., Akkerman, Jan-Willem N., Ciullo, Marina, Deloukas, Panos, Greinacher, Andreas, Jupe, Steve, Kamatani, Naoyuki, Khadake, Jyoti, Kooner, Jaspal S., Penninger, Josef, Prokopenko, Inga, Stemple, Derek, Toniolo, Daniela, Wernisch, Lorenz, Sanna, Serena, Hicks, Andrew A., Rendon, Augusto, Ferreira, Manuel A., Ouwehand, Willem H., and Soranzo, Nicole

Published
2011
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48. ACE Inhibitors, ARBs and Other Anti-Hypertensive Drugs and Novel COVID-19: An Association Study from the COVID Symptom Tracker App in 2,215,386 Individuals

Author

Dooley, Hannah, primary, Lee, Karla, additional, Freidin, Maxim, additional, Hemani, Gibran, additional, Roberts, Amy, additional, Lavigne du Cadet, Julian, additional, Visconti, Alessia, additional, Murray, Benjamin, additional, El-Sayed Moustafa, Julia, additional, Ni Lochlainn, Mary, additional, Zhang, Xinyuan, additional, Davies, Richard, additional, Falchi, Mario, additional, Small, Kerrin, additional, Hammond, Chris, additional, Davey Smith, George, additional, Wolf, Jonathan, additional, Spector, Tim, additional, and Steves, Claire, additional

Published
2020
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