866 results on '"Wiggs, Janey L."'
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2. POU6F2, a risk factor for glaucoma, myopia and dyslexia, labels specific populations of retinal ganglion cells
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Lin, Fangyu, Li, Ying, Wang, Jiaxing, Jardines, Sandra, King, Rebecca, Chrenek, Micah A., Wiggs, Janey L., Boatright, Jeffrey H., and Geisert, Eldon E.
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- 2024
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3. Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma
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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.
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- 2024
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4. The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population
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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.
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- 2024
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5. Large-scale multitrait genome-wide association analyses identify hundreds of glaucoma risk loci
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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
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- 2023
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6. Use of Diagnostic Codes for Primary Open-Angle Glaucoma Polygenic Risk Score Construction in Electronic Health Record–Linked Biobanks
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Tran, Jessica H., Kang, Joyce, Han, Elaine, Gupta, Urvi, Seresirikachorn, Kasem, Vy, Ha My T., Zhao, Yan, Rocheleau, Ghislain, Luo, Yuyang, Lee, Rachel, Do, Ron, Friedman, David S., Kang, Jae H., Wiggs, Janey L., Pasquale, Louis R., Segrè, Ayellet V., and Zebardast, Nazlee
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- 2024
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7. Association between Diabetes and Exfoliation Syndrome: A Systematic Review and Meta-Analysis of Observational Studies
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Yu, Megan, Hwang, Hannah H., Wiggs, Janey L., Pasquale, Louis R., and Kang, Jae H.
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- 2024
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8. Mechanosensitive ion channel gene survey suggests potential roles in primary open angle glaucoma
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Liu, Wendy W., Kinzy, Tyler G., Cooke Bailey, Jessica N., Xu, Zihe, Hysi, Pirro, and Wiggs, Janey L.
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- 2023
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9. Plasma metabolite profile for primary open-angle glaucoma in three US cohorts and the UK Biobank
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Zeleznik, Oana A., Kang, Jae H., Lasky-Su, Jessica, Eliassen, A. Heather, Frueh, Lisa, Clish, Clary B., Rosner, Bernard A., Elze, Tobias, Hysi, Pirro, Khawaja, Anthony, Wiggs, Janey L., and Pasquale, Louis R.
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- 2023
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10. A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma
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Verma, Shefali S., Gudiseva, Harini V., Chavali, Venkata R.M., Salowe, Rebecca J., Bradford, Yuki, Guare, Lindsay, Lucas, Anastasia, Collins, David W., Vrathasha, Vrathasha, Nair, Rohini M., Rathi, Sonika, Zhao, Bingxin, He, Jie, Lee, Roy, Zenebe-Gete, Selam, Bowman, Anita S., McHugh, Caitlin P., Zody, Michael C., Pistilli, Maxwell, Khachatryan, Naira, Daniel, Ebenezer, Murphy, Windell, Henderer, Jeffrey, Kinzy, Tyler G., Iyengar, Sudha K., Peachey, Neal S., Taylor, Kent D., Guo, Xiuqing, Chen, Yii-Der Ida, Zangwill, Linda, Girkin, Christopher, Ayyagari, Radha, Liebmann, Jeffrey, Chuka-Okosa, Chimd M., Williams, Susan E., Akafo, Stephen, Budenz, Donald L., Olawoye, Olusola O., Ramsay, Michele, Ashaye, Adeyinka, Akpa, Onoja M., Aung, Tin, Wiggs, Janey L., Ross, Ahmara G., Cui, Qi N., Addis, Victoria, Lehman, Amanda, Miller-Ellis, Eydie, Sankar, Prithvi S., Williams, Scott M., Ying, Gui-shuang, Cooke Bailey, Jessica, Rotter, Jerome I., Weinreb, Robert, Khor, Chiea Chuen, Hauser, Michael A., Ritchie, Marylyn D., and O’Brien, Joan M.
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- 2024
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11. Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries.
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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
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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.
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- 2021
12. The Association of Alcohol Consumption with Glaucoma and Related Traits: Findings from the UK Biobank
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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.
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- 2023
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13. Genetic testing and gene therapy in glaucoma
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Wiggs, Janey L., primary
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- 2023
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14. List of contributors
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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
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- 2023
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15. Molecular Mechanisms of Inherited Disease
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Wiggs, Janey L., Comander, Jason, Section editor, Vandenberghe, Luk, Section editor, Albert, Daniel M., editor, Miller, Joan W., editor, Azar, Dimitri T., editor, and Young, Lucy H., editor
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- 2022
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16. The Genetics of Common, Complex Diseases
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Cooke Bailey, Jessica N., Sobrin, Lucia, Wiggs, Janey L., Comander, Jason, Section editor, Vandenberghe, Luk, Section editor, Albert, Daniel M., editor, Miller, Joan W., editor, Azar, Dimitri T., editor, and Young, Lucy H., editor
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- 2022
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17. Genetic Testing
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Wiggs, Janey L., Place, Emily M., Comander, Jason, Section editor, Vandenberghe, Luk, Section editor, Albert, Daniel M., editor, Miller, Joan W., editor, Azar, Dimitri T., editor, and Young, Lucy H., editor
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- 2022
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18. Genetics of Glaucoma
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Wiggs, Janey L., Tsai, James C., Section editor, Sun, Yang, Section editor, Albert, Daniel M., editor, Miller, Joan W., editor, Azar, Dimitri T., editor, and Young, Lucy H., editor
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- 2022
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19. Multi-trait genome-wide association study identifies new loci associated with optic disc parameters
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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
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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.
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- 2019
20. Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry
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Consortium, The Genetics of Glaucoma in People of African Descent, Hauser, Michael A, Allingham, R Rand, Aung, Tin, Van Der Heide, Carly J, Taylor, Kent D, Rotter, Jerome I, Wang, Shih-Hsiu J, Bonnemaijer, Pieter WM, Williams, Susan E, Abdullahi, Sadiq M, Abu-Amero, Khaled K, Anderson, Michael G, Akafo, Stephen, Alhassan, Mahmoud B, Asimadu, Ifeoma, Ayyagari, Radha, Bakayoko, Saydou, Nyamsi, Prisca Biangoup, Bowden, Donald W, Bromley, William C, Budenz, Donald L, Carmichael, Trevor R, Challa, Pratap, Chen, Yii-Der Ida, Chuka-Okosa, Chimdi M, Bailey, Jessica N Cooke, Costa, Vital Paulino, Cruz, Dianne A, DuBiner, Harvey, Ervin, John F, Feldman, Robert M, Flamme-Wiese, Miles, Gaasterland, Douglas E, Garnai, Sarah J, Girkin, Christopher A, Guirou, Nouhoum, Guo, Xiuqing, Haines, Jonathan L, Hammond, Christopher J, Herndon, Leon, Hoffmann, Thomas J, Hulette, Christine M, Hydara, Abba, Igo, Robert P, Jorgenson, Eric, Kabwe, Joyce, Kilangalanga, Ngoy Janvier, Kizor-Akaraiwe, Nkiru, Kuchtey, Rachel W, Lamari, Hasnaa, Li, Zheng, Liebmann, Jeffrey M, Liu, Yutao, Loos, Ruth JF, Melo, Monica B, Moroi, Sayoko E, Msosa, Joseph M, Mullins, Robert F, Nadkarni, Girish, Napo, Abdoulaye, Ng, Maggie CY, Nunes, Hugo Freire, Obeng-Nyarkoh, Ebenezer, Okeke, Anthony, Okeke, Suhanya, Olaniyi, Olusegun, Olawoye, Olusola, Oliveira, Mariana Borges, Pasquale, Louise R, Perez-Grossmann, Rodolfo A, Pericak-Vance, Margaret A, Qin, Xue, Ramsay, Michele, Resnikoff, Serge, Richards, Julia E, Schimiti, Rui Barroso, Sim, Kar Seng, Sponsel, William E, Svidnicki, Paulo Vinicius, Thiadens, Alberta AHJ, Uche, Nkechinyere J, van Duijn, Cornelia M, de Vasconcellos, José Paulo Cabral, Wiggs, Janey L, Zangwill, Linda M, Risch, Neil, Milea, Dan, Ashaye, Adeyinka, Klaver, Caroline CW, Weinreb, Robert N, Koch, Allison E Ashley, Fingert, John H, and Khor, Chiea Chuen
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Neurosciences ,Human Genome ,Aging ,Genetics ,Eye Disease and Disorders of Vision ,Clinical Research ,Neurodegenerative ,2.1 Biological and endogenous factors ,Aetiology ,Adaptor Proteins ,Signal Transducing ,Aged ,Amyloid beta-Peptides ,Black People ,Case-Control Studies ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Glaucoma ,Open-Angle ,Humans ,Immunohistochemistry ,Male ,Meta-Analysis as Topic ,Middle Aged ,Polymorphism ,Single Nucleotide ,Risk Factors ,Genetics of Glaucoma in People of African Descent (GGLAD) Consortium ,Medical and Health Sciences ,General & Internal Medicine - Abstract
ImportancePrimary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders.ObjectivesTo perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma.Design, settings, and participantsA 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma.ExposuresGenetic variants associated with primary open-angle glaucoma.Main outcomes and measuresPresence of primary open-angle glaucoma. Genome-wide significance was defined as P C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P
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- 2019
21. Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.
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Genetics of Glaucoma in People of African Descent (GGLAD) Consortium, Hauser, Michael A, Allingham, R Rand, Aung, Tin, Van Der Heide, Carly J, Taylor, Kent D, Rotter, Jerome I, Wang, Shih-Hsiu J, Bonnemaijer, Pieter WM, Williams, Susan E, Abdullahi, Sadiq M, Abu-Amero, Khaled K, Anderson, Michael G, Akafo, Stephen, Alhassan, Mahmoud B, Asimadu, Ifeoma, Ayyagari, Radha, Bakayoko, Saydou, Nyamsi, Prisca Biangoup, Bowden, Donald W, Bromley, William C, Budenz, Donald L, Carmichael, Trevor R, Challa, Pratap, Chen, Yii-Der Ida, Chuka-Okosa, Chimdi M, Cooke Bailey, Jessica N, Costa, Vital Paulino, Cruz, Dianne A, DuBiner, Harvey, Ervin, John F, Feldman, Robert M, Flamme-Wiese, Miles, Gaasterland, Douglas E, Garnai, Sarah J, Girkin, Christopher A, Guirou, Nouhoum, Guo, Xiuqing, Haines, Jonathan L, Hammond, Christopher J, Herndon, Leon, Hoffmann, Thomas J, Hulette, Christine M, Hydara, Abba, Igo, Robert P, Jorgenson, Eric, Kabwe, Joyce, Kilangalanga, Ngoy Janvier, Kizor-Akaraiwe, Nkiru, Kuchtey, Rachel W, Lamari, Hasnaa, Li, Zheng, Liebmann, Jeffrey M, Liu, Yutao, Loos, Ruth JF, Melo, Monica B, Moroi, Sayoko E, Msosa, Joseph M, Mullins, Robert F, Nadkarni, Girish, Napo, Abdoulaye, Ng, Maggie CY, Nunes, Hugo Freire, Obeng-Nyarkoh, Ebenezer, Okeke, Anthony, Okeke, Suhanya, Olaniyi, Olusegun, Olawoye, Olusola, Oliveira, Mariana Borges, Pasquale, Louise R, Perez-Grossmann, Rodolfo A, Pericak-Vance, Margaret A, Qin, Xue, Ramsay, Michele, Resnikoff, Serge, Richards, Julia E, Schimiti, Rui Barroso, Sim, Kar Seng, Sponsel, William E, Svidnicki, Paulo Vinicius, Thiadens, Alberta AHJ, Uche, Nkechinyere J, van Duijn, Cornelia M, de Vasconcellos, José Paulo Cabral, Wiggs, Janey L, Zangwill, Linda M, Risch, Neil, Milea, Dan, Ashaye, Adeyinka, Klaver, Caroline CW, Weinreb, Robert N, Ashley Koch, Allison E, Fingert, John H, and Khor, Chiea Chuen
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Genetics of Glaucoma in People of African Descent (GGLAD) Consortium ,Humans ,Glaucoma ,Open-Angle ,Genetic Predisposition to Disease ,Adaptor Proteins ,Signal Transducing ,Immunohistochemistry ,Risk Factors ,Case-Control Studies ,Genotype ,Polymorphism ,Single Nucleotide ,Aged ,Middle Aged ,African Continental Ancestry Group ,Female ,Male ,Meta-Analysis as Topic ,Genome-Wide Association Study ,Amyloid beta-Peptides ,Eye Disease and Disorders of Vision ,Clinical Research ,Human Genome ,Aging ,Neurodegenerative ,Genetics ,Neurosciences ,2.1 Biological and endogenous factors ,General & Internal Medicine ,Medical and Health Sciences - Abstract
Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P
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- 2019
22. Association of a Primary Open-Angle Glaucoma Genetic Risk Score With Earlier Age at Diagnosis
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Fan, Bao Jian, Bailey, Jessica Cooke, Igo, Rob P, Kang, Jae H, Boumenna, Tahani, Brilliant, Murray H, Budenz, Donald L, Fingert, John H, Gaasterland, Terry, Gaasterland, Douglas, Hauser, Michael A, Kraft, Peter, Lee, Richard K, Lichter, Paul R, Liu, Yutao, Moroi, Syoko E, Myers, Jonathan S, Pericak-Vance, Margaret A, Realini, Anthony, Rhee, Douglas J, Richards, Julia E, Ritch, Robert, Schuman, Joel S, Scott, William K, Singh, Kuldev, Sit, Arthur J, Vollrath, Douglas, Weinreb, Robert N, Wollstein, Gadi, Zack, Donald J, Haines, Jonathan L, Pasquale, Louis R, and Wiggs, Janey L
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Neurosciences ,Clinical Research ,Human Genome ,Eye Disease and Disorders of Vision ,Neurodegenerative ,Genetics ,Aging ,Prevention ,2.1 Biological and endogenous factors ,Aetiology ,Opthalmology and Optometry ,Ophthalmology & Optometry - Abstract
ImportanceGenetic variants associated with primary open-angle glaucoma (POAG) are known to influence disease risk. However, the clinical effect of associated variants individually or in aggregate is not known. Genetic risk scores (GRS) examine the cumulative genetic load by combining individual genetic variants into a single measure, which is assumed to have a larger effect and increased power to detect relevant disease-related associations.ObjectiveTo investigate if a GRS that comprised 12 POAG genetic risk variants is associated with age at disease diagnosis.Design, setting, and participantsA cross-sectional study included individuals with POAG and controls from the Glaucoma Genes and Environment (GLAUGEN) study and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) study. A GRS was formulated using 12 variants known to be associated with POAG, and the alleles associated with increasing risk of POAG were aligned in the case-control sets. In case-only analyses, the association of the GRS with age at diagnosis was analyzed as an estimate of disease onset. Results from cohort-specific analyses were combined with meta-analysis. Data collection started in August 2012 for the NEIGHBOR cohort and in July 2008 for the GLAUGEN cohort and were analyzed starting in March 2018.Main outcomes and measuresAssociation of a 12 single-nucleotide polymorphism POAG GRS with age at diagnosis in individuals with POAG using linear regression.ResultsThe GLAUGEN study included 976 individuals with POAG and 1140 controls. The NEIGHBOR study included 2132 individuals with POAG and 2290 controls. For individuals with POAG, the mean (SD) age at diagnosis was 63.6 (9.8) years in the GLAUGEN cohort and 66.0 (13.7) years in the NEIGHBOR cohort. For controls, the mean (SD) age at enrollment was 65.5 (9.2) years in the GLAUGEN cohort and 68.9 (11.4) years in the NEIGHBOR cohort. All study participants were European white. The GRS was strongly associated with POAG risk in case-control analysis (odds ratio per 1-point increase in score = 1.24; 95% CI, 1.21-1.27; P = 3.4 × 10-66). In case-only analyses, each higher GRS unit was associated with a 0.36-year earlier age at diagnosis (β = -0.36; 95% CI, -0.56 to -0.16; P = 4.0 × 10-4). Individuals in the top 5% of the GRS had a mean (SD) age at diagnosis of 5.2 (12.8) years earlier than those in the bottom 5% GRS (61.4 [12.7] vs 66.6 [12.9] years; P = 5.0 × 10-4).Conclusions and relevanceA higher dose of POAG risk alleles was associated with an earlier age at glaucoma diagnosis. On average, individuals with POAG with the highest GRS had 5.2-year earlier age at diagnosis of disease. These results suggest that a GRS that comprised genetic variants associated with POAG could help identify patients with risk of earlier disease onset impacting screening and therapeutic strategies.
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- 2019
23. Long-term Alcohol Consumption and Risk of Exfoliation Glaucoma or Glaucoma Suspect Status among United States Health Professionals
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Hanyuda, Akiko, Rosner, Bernard A., Wiggs, Janey L., Negishi, Kazuno, Pasquale, Louis R., and Kang, Jae H.
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- 2023
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24. The Association of Physical Activity with Glaucoma and Related Traits in the UK Biobank
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Madjedi, Kian M., Stuart, Kelsey V., Chua, Sharon Y.L., Ramulu, Pradeep Y., Warwick, Alasdair, Luben, Robert N., Sun, Zihan, Chia, Mark A., Aschard, Hugues, Wiggs, Janey L., Kang, Jae H., Pasquale, Louis R., Foster, Paul J., and Khawaja, Anthony P.
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- 2023
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25. The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population
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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
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- 2024
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26. The Association of Female Reproductive Factors with Glaucoma and Related Traits: A Systematic Review
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Madjedi, Kian M., Stuart, Kelsey V., Chua, Sharon Y.L., Foster, Paul J., Strouthidis, Nicholas G., Luben, Robert N., Warwick, Alasdair N., Kang, Jae H., Wiggs, Janey L., Pasquale, Louis R., and Khawaja, Anthony P.
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- 2022
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27. Head and Neck Region Dermatological Ultraviolet-Related Cancers are Associated with Exfoliation Syndrome in a Clinic-Based Population
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Huang, Jeff J., Geduldig, Jack E., Jacobs, Erica B., Tai, Tak Yee T., Ahmad, Sumayya, Chadha, Nisha, Buxton, Douglas F., Vinod, Kateki, Wirostko, Barbara M., Kang, Jae H., Wiggs, Janey L., Ritch, Robert, and Pasquale, Louis R.
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- 2022
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28. Myocilin Mutations in Patients With Normal-Tension Glaucoma
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Alward, Wallace LM, van der Heide, Carly, Khanna, Cheryl L, Roos, Ben R, Sivaprasad, Sobha, Kam, Jason, Ritch, Robert, Lotery, Andrew, Igo, Robert P, Bailey, Jessica N Cooke, Stone, Edwin M, Scheetz, Todd E, Kwon, Young H, Pasquale, Louis R, Wiggs, Janey L, and Fingert, John H
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Neurosciences ,Clinical Research ,Neurodegenerative ,Eye Disease and Disorders of Vision ,Aging ,2.1 Biological and endogenous factors ,Aetiology ,Eye ,Aged ,Case-Control Studies ,Cytoskeletal Proteins ,Eye Proteins ,Female ,Glycoproteins ,Humans ,Intraocular Pressure ,Low Tension Glaucoma ,Male ,Middle Aged ,Mutation ,NEIGHBORHOOD Consortium ,Opthalmology and Optometry ,Ophthalmology & Optometry - Abstract
Importance:Mutations in the myocilin (MYOC) gene are the most common molecularly defined cause of primary open-angle glaucoma that typically occurs in patients with high intraocular pressures (IOP). One MYOC mutation, p.Gln368Ter, has been associated with as many as 1.6% of primary open-angle glaucoma cases that had a mean maximum recorded IOP of 30 mm Hg. However, to our knowledge, the role of the p.Gln368Ter mutation in patients with normal-tension glaucoma (NTG) with an IOP of 21 mm Hg or lower has not been investigated. Objective:To evaluate the role of the p.Gln368Ter MYOC mutation in patients with NTG. Design, Setting, and Participants:In this case-control study of the prevalence of the p.Gln368Ter mutation in patients with NTG, cohort 1 was composed of 772 patients with NTG and 2152 controls from the United States (Iowa, Minnesota, and New York) and England and cohort 2 was composed of 561 patients with NTG and 2606 controls from the Massachusetts Eye and Ear Infirmary and the NEIGHBORHOOD consortium. Genotyping was conducted using real-time polymerase chain reaction that was confirmed with Sanger sequencing, the imputation of genome-wide association study data, or an analysis of whole-exome sequence data. Data analysis occurred between April 2007 and April 2018. Main Outcomes and Measures:Comparison of the frequency of the p.Gln368Ter MYOC mutation between NTG cases and controls with the Fisher exact test. Results:Of 6091 total participants, 3346 (54.9%) were women and 5799 (95.2%) were white. We detected the p.Gln368Ter mutation in 7 of 772 patients with NTG (0.91%) and 7 of 2152 controls (0.33%) in cohort 1 (P = .03). In cohort 2, we detected the p.Gln368Ter mutation in 4 of 561 patients with NTG (0.71%) and 10 of 2606 controls (0.38%; P = .15). When the cohorts were analyzed as a group, the p.Gln368Ter mutation was associated with NTG (odds ratio, 2.3; 95% CI, 0.98-5.3; P = .04). Conclusions and Relevance:In cohorts 1 and 2, the p.Gln368Ter mutation in MYOC was found in patients with IOPs that were 21 mm Hg or lower (NTG), although at a frequency that is lower than previously detected in patients with higher IOP. These data suggest that the p.Gln368Ter mutation may be associated with glaucoma in patients with normal IOPs as well as in patients with IOPs that are greater than 21 mm Hg.
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- 2019
29. Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.
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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
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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.
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- 2019
30. Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations.
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Bonnemaijer, Pieter WM, Iglesias, Adriana I, Nadkarni, Girish N, Sanyiwa, Anna J, Hassan, Hassan G, Cook, Colin, GIGA Study Group, Simcoe, Mark, Taylor, Kent D, Schurmann, Claudia, Belbin, Gillian M, Kenny, Eimear E, Bottinger, Erwin P, van de Laar, Suzanne, Wiliams, Susan EI, Akafo, Stephen K, Ashaye, Adeyinka O, Zangwill, Linda M, Girkin, Christopher A, Ng, Maggie CY, Rotter, Jerome I, Weinreb, Robert N, Li, Zheng, Allingham, R Rand, Eyes of Africa Genetics Consortium, Nag, Abhishek, Hysi, Pirro G, Meester-Smoor, Magda A, Wiggs, Janey L, NEIGHBORHOOD Consortium, Hauser, Michael A, Hammond, Christopher J, Lemij, Hans G, Loos, Ruth JF, van Duijn, Cornelia M, Thiadens, Alberta AHJ, and Klaver, Caroline CW
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GIGA Study Group ,Eyes of Africa Genetics Consortium ,NEIGHBORHOOD Consortium ,Humans ,Glaucoma ,Open-Angle ,Vesicular Transport Proteins ,Aged ,Aged ,80 and over ,Middle Aged ,African Continental Ancestry Group ,Female ,Male ,Thioredoxin Reductase 2 ,Genome-Wide Association Study ,Genetic Loci ,Neurodegenerative ,Human Genome ,Aging ,Eye Disease and Disorders of Vision ,Genetics ,Neurosciences ,2.1 Biological and endogenous factors ,Genetics & Heredity ,Complementary and Alternative Medicine ,Paediatrics and Reproductive Medicine - Abstract
Primary open angle glaucoma (POAG) is a complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. We conducted a genome-wide association study in 1113 POAG cases and 1826 controls from Tanzanian, South African and African American study samples. Apart from confirming evidence of association at TXNRD2 (rs16984299; OR[T] 1.20; P = 0.003), we found that a genetic risk score combining the effects of the 15 previously reported POAG loci was significantly associated with POAG in our samples (OR 1.56; 95% CI 1.26-1.93; P = 4.79 × 10-5). By genome-wide association testing we identified a novel candidate locus, rs141186647, harboring EXOC4 (OR[A] 0.48; P = 3.75 × 10-8), a gene transcribing a component of the exocyst complex involved in vesicle transport. The low frequency and high degree of genetic heterogeneity at this region hampered validation of this finding in predominantly West-African replication sets. Our results suggest that established genetic risk factors play a role in African POAG, however, they do not explain the higher disease load. The high heterogeneity within Africans remains a challenge to identify the genetic commonalities for POAG in this ethnicity, and demands studies of extremely large size.
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- 2018
31. The genetic basis for adult onset glaucoma: Recent advances and future directions
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Wang, Zhenxun, Wiggs, Janey L., Aung, Tin, Khawaja, Anthony P., and Khor, Chiea Chuen
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- 2022
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32. How genome-wide association studies transform care for patients at risk of glaucoma.
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Zebardast, Nazlee and Wiggs, Janey L.
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GLAUCOMA diagnosis ,RISK assessment ,SERIAL publications ,GLAUCOMA ,OPTICAL coherence tomography ,MEDICAL care ,ONCOGENES ,BLINDNESS ,GENOMES ,BIOMARKERS ,GENETIC testing ,DISEASE risk factors - Published
- 2024
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33. Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.
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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
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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.
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- 2018
34. Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets
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Cooke Bailey, Jessica N, Gharahkhani, Puya, Kang, Jae H, Butkiewicz, Mariusz, Sullivan, David A, Weinreb, Robert N, Aschard, Hugues, 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, Robert P, Song, Yeunjoo E, Hark, Lisa, Ritch, Robert, Rhee, Douglas J, Vollrath, Douglas, Zack, Donald J, Medeiros, Felipe, Vajaranant, Thasarat S, Chasman, Daniel I, Christen, William G, Pericak-Vance, Margaret A, Liu, Yutao, Kraft, Peter, Richards, Julia E, Rosner, Bernard A, Hauser, Michael A, Craig, Jamie E, Burdon, Kathryn P, Hewitt, Alex W, Mackey, David A, Haines, Jonathan L, MacGregor, Stuart, Wiggs, Janey L, and Pasquale, Louis R
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Genetics ,Neurodegenerative ,Aging ,2.1 Biological and endogenous factors ,Aetiology ,Datasets as Topic ,Female ,Gene Frequency ,Genome-Wide Association Study ,Genotype ,Glaucoma ,Open-Angle ,Humans ,Intraocular Pressure ,Low Tension Glaucoma ,Male ,Metabolic Networks and Pathways ,Middle Aged ,Polymorphism ,Single Nucleotide ,Testosterone ,primary open-angle glaucoma ,testosterone ,genetics ,pathway analysis ,Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG) Consortium ,Biological Sciences ,Medical and Health Sciences ,Ophthalmology & Optometry - Abstract
Purpose:Sex hormones may be associated with primary open-angle glaucoma (POAG), although the mechanisms are unclear. We previously observed that gene variants involved with estrogen metabolism were collectively associated with POAG in women but not men; here we assessed gene variants related to testosterone metabolism collectively and POAG risk. Methods:We used two datasets: one from the United States (3853 cases and 33,480 controls) and another from Australia (1155 cases and 1992 controls). Both datasets contained densely called genotypes imputed to the 1000 Genomes reference panel. We used pathway- and gene-based approaches with Pathway Analysis by Randomization Incorporating Structure (PARIS) software to assess the overall association between a panel of single nucleotide polymorphisms (SNPs) in testosterone metabolism genes and POAG. In sex-stratified analyses, we evaluated POAG overall and POAG subtypes defined by maximum IOP (high-tension [HTG] or normal tension glaucoma [NTG]). Results:In the US dataset, the SNP panel was not associated with POAG (permuted P = 0.77), although there was an association in the Australian sample (permuted P = 0.018). In both datasets, the SNP panel was associated with POAG in men (permuted P ≤ 0.033) and not women (permuted P ≥ 0.42), but in gene-based analyses, there was no consistency on the main genes responsible for these findings. In both datasets, the testosterone pathway association with HTG was significant (permuted P ≤ 0.011), but again, gene-based analyses showed no consistent driver gene associations. Conclusions:Collectively, testosterone metabolism pathway SNPs were consistently associated with the high-tension subtype of POAG in two datasets.
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- 2018
35. Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets.
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Bailey, Jessica N Cooke, Gharahkhani, Puya, Kang, Jae H, Butkiewicz, Mariusz, Sullivan, David A, Weinreb, Robert N, Aschard, Hugues, 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, Robert P, Song, Yeunjoo E, Hark, Lisa, Ritch, Robert, Rhee, Douglas J, Vollrath, Douglas, Zack, Donald J, Medeiros, Felipe, Vajaranant, Thasarat S, Chasman, Daniel I, Christen, William G, Pericak-Vance, Margaret A, Liu, Yutao, Kraft, Peter, Richards, Julia E, Rosner, Bernard A, Hauser, Michael A, Craig, Jamie E, Burdon, Kathryn P, Hewitt, Alex W, Mackey, David A, Haines, Jonathan L, MacGregor, Stuart, Wiggs, Janey L, Pasquale, Louis R, and Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG) Consortium
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Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG) Consortium ,Humans ,Glaucoma ,Open-Angle ,Testosterone ,Intraocular Pressure ,Gene Frequency ,Genotype ,Polymorphism ,Single Nucleotide ,Middle Aged ,Female ,Male ,Metabolic Networks and Pathways ,Genome-Wide Association Study ,Low Tension Glaucoma ,Datasets as Topic ,primary open-angle glaucoma ,testosterone ,genetics ,pathway analysis ,Glaucoma ,Open-Angle ,Polymorphism ,Single Nucleotide ,Biological Sciences ,Medical and Health Sciences ,Ophthalmology & Optometry - Abstract
Purpose:Sex hormones may be associated with primary open-angle glaucoma (POAG), although the mechanisms are unclear. We previously observed that gene variants involved with estrogen metabolism were collectively associated with POAG in women but not men; here we assessed gene variants related to testosterone metabolism collectively and POAG risk. Methods:We used two datasets: one from the United States (3853 cases and 33,480 controls) and another from Australia (1155 cases and 1992 controls). Both datasets contained densely called genotypes imputed to the 1000 Genomes reference panel. We used pathway- and gene-based approaches with Pathway Analysis by Randomization Incorporating Structure (PARIS) software to assess the overall association between a panel of single nucleotide polymorphisms (SNPs) in testosterone metabolism genes and POAG. In sex-stratified analyses, we evaluated POAG overall and POAG subtypes defined by maximum IOP (high-tension [HTG] or normal tension glaucoma [NTG]). Results:In the US dataset, the SNP panel was not associated with POAG (permuted P = 0.77), although there was an association in the Australian sample (permuted P = 0.018). In both datasets, the SNP panel was associated with POAG in men (permuted P ≤ 0.033) and not women (permuted P ≥ 0.42), but in gene-based analyses, there was no consistency on the main genes responsible for these findings. In both datasets, the testosterone pathway association with HTG was significant (permuted P ≤ 0.011), but again, gene-based analyses showed no consistent driver gene associations. Conclusions:Collectively, testosterone metabolism pathway SNPs were consistently associated with the high-tension subtype of POAG in two datasets.
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- 2018
36. Genomic locus modulating corneal thickness in the mouse identifies POU6F2 as a potential risk of developing glaucoma.
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King, Rebecca, Struebing, Felix L, Li, Ying, Wang, Jiaxing, Koch, Allison Ashley, Cooke Bailey, Jessica N, Gharahkhani, Puya, International Glaucoma Genetics Consortium, NEIGHBORHOOD Consortium, MacGregor, Stuart, Allingham, R Rand, Hauser, Michael A, Wiggs, Janey L, and Geisert, Eldon E
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International Glaucoma Genetics Consortium ,NEIGHBORHOOD Consortium ,Retinal Ganglion Cells ,Cornea ,Cells ,Cultured ,Animals ,Mice ,Inbred C57BL ,Mice ,Inbred DBA ,Mice ,Transgenic ,Humans ,Mice ,Glaucoma ,Disease Models ,Animal ,Genetic Predisposition to Disease ,Risk Factors ,Chromosome Mapping ,Apoptosis ,Pregnancy ,Polymorphism ,Single Nucleotide ,Female ,Male ,POU Domain Factors ,Embryo ,Mammalian ,Genome-Wide Association Study ,Genetic Loci ,Corneal Pachymetry ,Cells ,Cultured ,Disease Models ,Animal ,Embryo ,Mammalian ,Inbred C57BL ,Inbred DBA ,Transgenic ,Polymorphism ,Single Nucleotide ,Genetics ,Developmental Biology - Abstract
Central corneal thickness (CCT) is one of the most heritable ocular traits and it is also a phenotypic risk factor for primary open angle glaucoma (POAG). The present study uses the BXD Recombinant Inbred (RI) strains to identify novel quantitative trait loci (QTLs) modulating CCT in the mouse with the potential of identifying a molecular link between CCT and risk of developing POAG. The BXD RI strain set was used to define mammalian genomic loci modulating CCT, with a total of 818 corneas measured from 61 BXD RI strains (between 60-100 days of age). The mice were anesthetized and the eyes were positioned in front of the lens of the Phoenix Micron IV Image-Guided OCT system or the Bioptigen OCT system. CCT data for each strain was averaged and used to QTLs modulating this phenotype using the bioinformatics tools on GeneNetwork (www.genenetwork.org). The candidate genes and genomic loci identified in the mouse were then directly compared with the summary data from a human POAG genome wide association study (NEIGHBORHOOD) to determine if any genomic elements modulating mouse CCT are also risk factors for POAG.This analysis revealed one significant QTL on Chr 13 and a suggestive QTL on Chr 7. The significant locus on Chr 13 (13 to 19 Mb) was examined further to define candidate genes modulating this eye phenotype. For the Chr 13 QTL in the mouse, only one gene in the region (Pou6f2) contained nonsynonymous SNPs. Of these five nonsynonymous SNPs in Pou6f2, two resulted in changes in the amino acid proline which could result in altered secondary structure affecting protein function. The 7 Mb region under the mouse Chr 13 peak distributes over 2 chromosomes in the human: Chr 1 and Chr 7. These genomic loci were examined in the NEIGHBORHOOD database to determine if they are potential risk factors for human glaucoma identified using meta-data from human GWAS. The top 50 hits all resided within one gene (POU6F2), with the highest significance level of p = 10-6 for SNP rs76319873. POU6F2 is found in retinal ganglion cells and in corneal limbal stem cells. To test the effect of POU6F2 on CCT we examined the corneas of a Pou6f2-null mice and the corneas were thinner than those of wild-type littermates. In addition, these POU6F2 RGCs die early in the DBA/2J model of glaucoma than most RGCs. Using a mouse genetic reference panel, we identified a transcription factor, Pou6f2, that modulates CCT in the mouse. POU6F2 is also found in a subset of retinal ganglion cells and these RGCs are sensitive to injury.
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- 2018
37. Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma: a multi-cohort analysis
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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
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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.
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- 2017
38. Genetic Associations of Primary Angle-Closure Disease
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Liang, Yu Jing, primary, Wang, Yu Yao, additional, Rong, Shi Song, additional, Chen, Zhen Ji, additional, Chen, Shu Ying, additional, Tham, Jenson A., additional, Chan, Poemen P., additional, Yam, Jason C., additional, Wiggs, Janey L., additional, Pang, Chi Pui, additional, Tham, Clement C., additional, and Chen, Li Jia, additional
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- 2024
- Full Text
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39. Polygenic Risk Scores for Glaucoma Onset in the Ocular Hypertension Treatment Study
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Singh, Rishabh K., primary, Zhao, Yan, additional, Elze, Tobias, additional, Fingert, John, additional, Gordon, Mae, additional, Kass, Michael A., additional, Luo, Yuyang, additional, Pasquale, Louis R., additional, Scheetz, Todd, additional, Segrè, Ayellet V., additional, Wiggs, Janey L., additional, and Zebardast, Nazlee, additional
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- 2024
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40. Genetic Basis of Pigment Dispersion Syndrome and Pigmentary Glaucoma: An Update and Functional Insights
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Rong, Shisong, primary, Yu, Xinting, additional, and Wiggs, Janey L., additional
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- 2024
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- View/download PDF
41. Age at natural menopause genetic risk score in relation to age at natural menopause and primary open-angle glaucoma in a US-based sample
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Pasquale, Louis R, Aschard, Hugues, Kang, Jae H, Bailey, Jessica N Cooke, Lindström, Sara, Chasman, Daniel I, Christen, William G, Allingham, R Rand, Ashley-Koch, Allison, Lee, Richard K, Moroi, Sayoko E, Brilliant, Murray H, Wollstein, Gadi, Schuman, Joel S, Fingert, John, Budenz, Donald L, Realini, Tony, Gaasterland, Terry, Gaasterland, Douglas, Scott, William K, Singh, Kuldev, Sit, Arthur J, Igo, Robert P, Song, Yeunjoo E, Hark, Lisa, Ritch, Robert, Rhee, Douglas J, Gulati, Vikas, Havens, Shane, Vollrath, Douglas, Zack, Donald J, Medeiros, Felipe, Weinreb, Robert N, Pericak-Vance, Margaret A, Liu, Yutao, Kraft, Peter, Richards, Julia E, Rosner, Bernard A, Hauser, Michael A, Haines, Jonathan L, and Wiggs, Janey L
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Epidemiology ,Biomedical and Clinical Sciences ,Health Sciences ,Ophthalmology and Optometry ,Human Genome ,Neurosciences ,Neurodegenerative ,Genetics ,Eye Disease and Disorders of Vision ,Aging ,Good Health and Well Being ,Age Factors ,Female ,Genetic Variation ,Genotype ,Glaucoma ,Open-Angle ,Humans ,Menopause ,Middle Aged ,Risk Assessment ,Risk Factors ,United States ,Age at natural menopause ,Genetic risk score ,Primary open-angle glaucoma ,Medical and Health Sciences ,Obstetrics & Reproductive Medicine ,Biomedical and clinical sciences ,Health sciences ,Psychology - Abstract
ObjectiveSeveral attributes of female reproductive history, including age at natural menopause (ANM), have been related to primary open-angle glaucoma (POAG). We assembled 18 previously reported common genetic variants that predict ANM to determine their association with ANM or POAG.MethodsUsing data from the Nurses' Health Study (7,143 women), we validated the ANM weighted genetic risk score in relation to self-reported ANM. Subsequently, to assess the relation with POAG, we used data from 2,160 female POAG cases and 29,110 controls in the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (NEIGHBORHOOD), which consists of 8 datasets with imputed genotypes to 5.6+ million markers. Associations with POAG were assessed in each dataset, and site-specific results were meta-analyzed using the inverse weighted variance method.ResultsThe genetic risk score was associated with self-reported ANM (P = 2.2 × 10) and predicted 4.8% of the variance in ANM. The ANM genetic risk score was not associated with POAG (Odds Ratio (OR) = 1.002; 95% Confidence Interval (CI): 0.998, 1.007; P = 0.28). No single genetic variant in the panel achieved nominal association with POAG (P ≥0.20). Compared to the middle 80 percent, there was also no association with the lowest 10 percentile or highest 90 percentile of genetic risk score with POAG (OR = 0.75; 95% CI: 0.47, 1.21; P = 0.23 and OR = 1.10; 95% CI: 0.72, 1.69; P = 0.65, respectively).ConclusionsA genetic risk score predicting 4.8% of ANM variation was not related to POAG; thus, genetic determinants of ANM are unlikely to explain the previously reported association between the two phenotypes.
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- 2017
42. Genome-wide association study identifies WNT7B as a novel locus for central corneal thickness in Latinos
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Gao, Xiaoyi, Nannini, Drew R, Corrao, Kristen, Torres, Mina, Chen, Yii-Der I, Fan, Bao J, Wiggs, Janey L, Consortium, International Glaucoma Genetics, Taylor, Kent D, Gauderman, W James, Rotter, Jerome I, and Varma, Rohit
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Biological Sciences ,Genetics ,Human Genome ,Eye Disease and Disorders of Vision ,Clinical Research ,Aging ,Aetiology ,2.1 Biological and endogenous factors ,Eye ,Adult ,Aged ,Cornea ,Corneal Pachymetry ,Female ,Genetic Loci ,Genome-Wide Association Study ,Genotype ,Glaucoma ,Glaucoma ,Open-Angle ,Hispanic or Latino ,Humans ,Keratoconus ,Los Angeles ,Male ,Middle Aged ,Polymorphism ,Single Nucleotide ,Wnt Proteins ,International Glaucoma Genetics Consortium ,Medical and Health Sciences ,Genetics & Heredity - Abstract
The cornea is the outermost layer of the eye and is a vital component of focusing incoming light on the retina. Central corneal thickness (CCT) is now recognized to have a significant role in ocular health and is a risk factor for various ocular diseases, such as keratoconus and primary open angle glaucoma. Most previous genetic studies utilized European and Asian subjects to identify genetic loci associated with CCT. Minority populations, such as Latinos, may aid in identifying additional loci and improve our understanding of the genetic architecture of CCT. In this study, we conducted a genome-wide association study (GWAS) in Latinos, a traditionally understudied population in genetic research, to further identify loci contributing to CCT. Study participants were genotyped using either the Illumina OmniExpress BeadChip (∼730K markers) or the Illumina Hispanic/SOL BeadChip (∼2.5 million markers). All study participants were 40 years of age and older. We assessed the association between individual single nucleotide polymorphisms (SNPs) and CCT using linear regression, adjusting for age, gender and principal components of genetic ancestry. To expand genomic coverage and to interrogate additional SNPs, we imputed SNPs from the 1000 Genomes Project reference panels. We identified a novel SNP, rs10453441 (P = 6.01E-09), in an intron of WNT7B that is associated with CCT. Furthermore, WNT7B is expressed in the human cornea. We also replicated 11 previously reported loci, including IBTK, RXRA-COL5A1, COL5A1, FOXO1, LRRK1 and ZNF469 (P
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- 2016
43. Thrombospondin 1 missense alleles induce extracellular matrix protein aggregation and TM dysfunction in congenital glaucoma
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Fu, Haojie, Siggs, Owen M., Knight, Lachlan S.W., Staffieri, Sandra E., Ruddle, Jonathan B., Birsner, Amy E., Collantes, Edward Ryan, Craig, Jamie E., Wiggs, Janey L., and D'Amato, Robert J.
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Genetic disorders -- Development and progression ,Glycoproteins -- Genetic aspects -- Health aspects ,Extracellular matrix -- Health aspects -- Physiological aspects ,Glaucoma in children -- Development and progression -- Genetic aspects ,Allelomorphism -- Research ,Pediatric research ,Health care industry - Abstract
Glaucoma is a highly heritable disease that is a leading cause of blindness worldwide. Here, we identified heterozygous thrombospondin 1 (THBS1) missense alleles altering p.Arg1034, a highly evolutionarily conserved amino acid, in 3 unrelated and ethnically diverse families affected by congenital glaucoma, a severe form of glaucoma affecting children. [Thbs1.sup.R1034C]-mutant mice had elevated intraocular pressure (IOP), reduced ocular fluid outflow, and retinal ganglion cell loss. Histology revealed an abundant, abnormal extracellular accumulation of THBS1 with abnormal morphology of juxtacanalicular trabecular meshwork (TM), an ocular tissue critical for aqueous fluid outflow. Functional characterization showed that the THBS1 missense alleles found in affected individuals destabilized the THBS1 C-terminus, causing protein misfolding and extracellular aggregation. Analysis using a range of amino acid substitutions at position R1034 showed that the extent of aggregation was correlated with the change in protein-folding free energy caused by variations in amino acid structure. Extracellular matrix (ECM) proteins, especially fibronectin, which bind to THBS1, also accumulated within THBS1 deposits. These results show that missense variants altering THBS1 p.Arg1034 can cause elevated IOP through a mechanism involving impaired TM fluid outflow in association with accumulation of aggregated THBS1 in the ECM of juxtacanalicular meshwork with altered morphology., Introduction Glaucoma is a progressive blinding disease that causes loss of retinal ganglion cells (RGCs) and irreversible degeneration of the optic nerve. Elevated intraocular pressure (IOP), currently the only modifiable [...]
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- 2022
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44. Relationship Between Oral Health and Glaucoma Traits in the United Kingdom.
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Lee, Rachel H., Kang, Jae H., Wiggs, Janey L., Wagner, Siegfried K., Khawaja, Anthony P., and Pasquale, Louis R.
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- 2024
- Full Text
- View/download PDF
45. Assessing the Association of Mitochondrial Genetic Variation With Primary Open-Angle Glaucoma Using Gene-Set AnalysesMitochondrial Genetic Variation and POAG
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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
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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.
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- 2016
46. A Common Variant in MIR182 Is Associated With Primary Open-Angle Glaucoma in the NEIGHBORHOOD ConsortiumAssociation of miR-182 and POAG in NEIGHBORHOOD
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Liu, Yutao, Bailey, Jessica Cooke, Helwa, Inas, Dismuke, W Michael, Cai, Jingwen, Drewry, Michelle, Brilliant, Murray H, Budenz, Donald L, Christen, William G, Chasman, Daniel I, Fingert, John H, Gaasterland, Douglas, Gaasterland, Terry, Gordon, Mae O, Igo, Robert P, Kang, Jae H, Kass, Michael A, Kraft, Peter, Lee, Richard K, Lichter, Paul, Moroi, Sayoko E, Realini, Anthony, Richards, Julia E, Ritch, Robert, Schuman, Joel S, Scott, William K, Singh, Kuldev, Sit, Arthur J, Song, Yeunjoo E, Vollrath, Douglas, Weinreb, Robert, Medeiros, Felipe, Wollstein, Gadi, Zack, Donald J, Zhang, Kang, Pericak-Vance, Margaret A, Gonzalez, Pedro, Stamer, W Daniel, Kuchtey, John, Kuchtey, Rachel W, Allingham, R Rand, Hauser, Michael A, Pasquale, Louis R, Haines, Jonathan L, and Wiggs, Janey L
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Neurosciences ,Aging ,Genetics ,Neurodegenerative ,Eye Disease and Disorders of Vision ,Biotechnology ,Human Genome ,2.1 Biological and endogenous factors ,geographic atrophy ,age-related macular degeneration ,animal models ,Aqueous Humor ,Humans ,Glaucoma ,Open-Angle ,Genetic Predisposition to Disease ,MicroRNAs ,RNA ,Polymerase Chain Reaction ,Gene Expression Regulation ,Intraocular Pressure ,Gene Frequency ,Genotype ,Alleles ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,Male ,Exosomes ,Biological Sciences ,Medical and Health Sciences ,Ophthalmology & Optometry - Abstract
PurposeNoncoding microRNAs (miRNAs) have been implicated in the pathogenesis of glaucoma. We aimed to identify common variants in miRNA coding genes (MIR) associated with primary open-angle glaucoma (POAG).MethodsUsing the NEIGHBORHOOD data set (3853 cases/33,480 controls with European ancestry), we first assessed the relation between 85 variants in 76 MIR genes and overall POAG. Subtype-specific analyses were performed in high-tension glaucoma (HTG) and normal-tension glaucoma subsets. Second, we examined the expression of miR-182, which was associated with POAG, in postmortem human ocular tissues (ciliary body, cornea, retina, and trabecular meshwork [TM]), using miRNA sequencing (miRNA-Seq) and droplet digital PCR (ddPCR). Third, miR-182 expression was also examined in human aqueous humor (AH) by using miRNA-Seq. Fourth, exosomes secreted from primary human TM cells were examined for miR-182 expression by using miRNA-Seq. Fifth, using ddPCR we compared miR-182 expression in AH between five HTG cases and five controls.ResultsOnly rs76481776 in MIR182 gene was associated with POAG after adjustment for multiple comparisons (odds ratio [OR] = 1.23, 95% confidence interval [CI]: 1.11-1.42, P = 0.0002). Subtype analysis indicated that the association was primarily in the HTG subset (OR = 1.26, 95% CI: 1.08-1.47, P = 0.004). The risk allele T has been associated with elevated miR-182 expression in vitro. Data from ddPCR and miRNA-Seq confirmed miR-182 expression in all examined ocular tissues and TM-derived exosomes. Interestingly, miR-182 expression in AH was 2-fold higher in HTG patients than nonglaucoma controls (P = 0.03) without controlling for medication treatment.ConclusionsOur integrative study is the first to associate rs76481776 with POAG via elevated miR-182 expression.
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- 2016
47. Erratum.
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Liu, Yutao, Bailey, Jessica Cooke, Helwa, Inas, Dismuke, W Michael, Cai, Jingwen, Drewry, Michelle, Brilliant, Murray H, Budenz, Donald L, Christen, William G, Chasman, Daniel I, Fingert, John H, Gaasterland, Douglas, Gaasterland, Terry, Gordon, Mae O, Igo, Robert P, Kang, Jae H, Kass, Michael A, Kraft, Peter, Lee, Richard K, Lichter, Paul, Moroi, Sayoko E, Realini, Anthony, Richards, Julia E, Ritch, Robert, Schuman, Joel S, Scott, William K, Singh, Kuldev, Sit, Arthur J, Song, Yeunjoo E, Vollrath, Douglas, Weinreb, Robert, Medeiros, Felipe, Wollstein, Gadi, Zack, Donald J, Zhang, Kang, Pericak-Vance, Margaret A, Gonzalez, Pedro, Stamer, W Daniel, Kuchtey, John, Kuchtey, Rachel W, Allingham, R Rand, Hauser, Michael A, Pasquale, Louis R, Haines, Jonathan L, and Wiggs, Janey L
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Ophthalmology & Optometry ,Biological Sciences ,Medical and Health Sciences - Published
- 2016
48. Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma
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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
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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.
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- 2016
49. Exome-based investigation of the genetic basis of human pigmentary glaucoma
- Author
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van der Heide, Carly, Goar, Wes, Meyer, Kacie J., Alward, Wallace L. M., Boese, Erin A., Sears, Nathan C., Roos, Ben R., Kwon, Young H., DeLuca, Adam P., Siggs, Owen M., Gonzaga-Jauregui, Claudia, Sheffield, Val C., Wang, Kai, Stone, Edwin M., Mullins, Robert F., Anderson, Michael G., Fan, Bao Jian, Ritch, Robert, Craig, Jamie E., Wiggs, Janey L., Scheetz, Todd E., and Fingert, John H.
- Published
- 2021
- Full Text
- View/download PDF
50. Molecular Mechanisms of Inherited Disease
- Author
-
Wiggs, Janey L., primary
- Published
- 2021
- Full Text
- View/download PDF
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