Genetic risks for age-related macular degeneration
- Date:
- January 14, 2025
- Source:
- Case Western Reserve University
- Summary:
- Age-related macular degeneration (AMD), which affects about 200 million people worldwide and can result in legal blindness, impairs an area of the eye (retina) used for reading, driving and many other critical daily tasks. A new study of large existing patient datasets indicates genetic and demographic factors that increase the risk for developing AMD.
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Age-related macular degeneration (AMD), which affects about 200 million people worldwide and can result in legal blindness, impairs an area of the eye (retina) used for reading, driving and many other critical daily tasks.
A new study of large existing patient datasets indicates genetic and demographic factors that increase the risk for developing AMD.
In the study, recently published in Nature Genetics, a team of scientists worked with the Million Veteran Program (MVP) of the VA Office of Research and Development, a large biobank of veterans recruited at more than 60 U.S. Department of Veterans Affairs (VA) medical centers nationally, to examine demographic, lifestyle, clinical and genetic risk profiles for AMD.
Their study focusedon more than 287,000 veterans enrolled in MVP and integrated findings with results from several other independent biobanks to define the largest study of genetic risk for AMD and the first to include populations of diverse ancestry.
"An important aspect of our study is the inclusion of veterans of African or Hispanic ancestry in the MVP -- groups that have not been well-studied in prior genetic studies of AMD," said Sudha Iyengar, a professor and vice chair of research in the Department of Population and Quantitative Health Sciences at the Case Western Reserve University School of Medicine. "This diverse population is a unique resource to identify clues to develop therapeutics for AMD, a condition for which few effective treatments are available."
The collective human genome shared by all ancestral groups worldwide contains discrete signatures for higher AMD risk in those of European descent, compared to those of African or Hispanic ancestry.
"By increasing the size of the study population," Sudha said, "the research provided additional information to identify genetic markers with more modest but potentially important biological contributions to the likelihood that an individual will -- or won't -- develop AMD. The study also found an increased number of genes linked to AMD, from 34 that were identified previously, to 60."
They also confirmed earlier beliefs that a history of smoking or alcohol use increases the likelihood of developing AMD. Although about 90% of the MVP are male enrollees, the researchers were able to confirm prior observations that women are more susceptible to AMD than men.
Sudha co-led the research with the late Robert Igo Jr., Dana Crawford and Jessica Cooke Bailey at the School of Medicine. They collaborated with Neal Peachey, associate chief of staff for research of the VA Northeast Ohio Healthcare System and professor of ophthalmic research at Cleveland Clinic Cole Eye Institute. The work was supported by grants to Peachey from the VA Office of Research and Development.
The study involved scientists from several VA medical centers, including Bryan Gorman and Saiju Pyarajan (both from VA Boston Healthcare System), Christopher Halladay and Wun-Shieh Wu (both from Providence VA Medical Center) and Pannos Roussos and Georgios Vodulakis (both from Mt. Sinai and Bronx VA), "who played key roles in integrating data from multiple health systems, cohorts and data types to create new knowledge of AMD biology," Sudha said.
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Materials provided by Case Western Reserve University. Note: Content may be edited for style and length.
Journal Reference:
- Bryan R. Gorman, Georgios Voloudakis, Robert P. Igo, Tyler Kinzy, Christopher W. Halladay, Tim B. Bigdeli, Biao Zeng, Sanan Venkatesh, Jessica N. Cooke Bailey, Dana C. Crawford, Kyriacos Markianos, Frederick Dong, Patrick A. Schreiner, Wen Zhang, Lars G. Fritsche, Wilmar Igl, Jessica N. Cooke Bailey, Felix Grassman, Sebanti Sengupta, Jennifer L. Bragg-Gresham, Kathryn P. Burdon, Scott J. Hebring, Cindy Wen, Mathias Gorski, Ivana K. Kim, David Cho, Donald Zack, Eric Souied, Hendrik P. N. Scholl, Elisa Bala, Kristine E. Lee, David J. Hunter, Rebecca J. Sardell, Paul Mitchell, Joanna E. Merriam, Valentina Cipriani, Joshua D. Hoffman, Tina Schick, Yara T. E. Lechanteur, Robyn H. Guymer, Matthew P. Johnson, Yingda Jiang, Chloe M. Stanton, Gabriëlle H. S. Buitendijk, Xiaowei Zhan, Alan M. Kwong, Alexis Boleda, Matthew Brooks, Linn Gieser, Rinki Ratnapriya, Kari E. Branham, Johanna R. Foerster, John R. Heckenlively, Mohammad I. Othman, Brendan J. Vote, Helena Hai Liang, Emmanuelle Souzeau, Ian L. McAllister, Timothy Isaacs, Janette Hall, Stewart Lake, David A. Mackey, Ian J. Constable, Jamie E. Craig, Terrie Kitchner, Zhenglin Yang, Zhiquang Su, Hongrong Luo, Daniel Chen, Ouyang Ouyang, Ken Flagg, Daniel Lin, Guanping Mao, Henry Ferreyra, Klaus Stark, Claudia Nvon Strachwitz, Armin Wolf, Caroline Brandl, Guenther Rudolph, Matthias Olden, Margaux A. Morrison, Deniste J. Morgan, Matthew Schu, Jeeyun Ahn, Giuliana Silvestri, Evangelia E. Tsironi, Kyu Hyung Park, Lindsay A. Farrer, Anton Orlin, Alexander Brucker, Mingyao Li, Christine A. Curcio, Saddek Mohand-Saïd, José-Alain Sahel, Isabelle Audo, Mustapha Benchaboune, Angela J. Cree, Christina A. Rennie, Srinivas V. Goverdhan, Michelle Grunin, Shira Hagbi-Levi, Peter Campochiaro, Nicholas Katsanis, Frank G. Holz, Frédéric Blond, Hélène Blanché, Jean-François Deleuze, Robert P. Igo, Barbara Truitt, Stacy M. Meuer, Chelsea E. Myers, Emily L. Moore, Ronald Klein, Michael A. Hauser, Eric A. Postel, Monique D. Courtenay, Stephen G. Schwartz, Jaclyn L. Kovach, William K. Scott, Gerald Liew, Ava G. Tan, Bamini Gopinath, John C. Merriam, R. Theodore Smith, Jane C. Khan, Humma Shahidi, Anthony T. Moore, J. Allie McGrath, Reneé Laux, Milam A. Brantley, Anita Agarwal, Lebriz Ersoy, Albert Caramoy, Thomas Langmann, Nicole T. M. Saksens, Eiko K. deJohn, Carel B. Hoyng, Melinda S. Cain, Andrea J. Richardson, Tammy M. Martin, John Blangero, Daniel E. Weeks, Bal Dhillon, Cornelia M. van Duijn, Kimberly F. Doheny, Jane Romm, Caroline C. W. Klaver, Caroline Hayward, Michael B. Gorin, Michael L. Klein, Paul N. Baird, Anneke I. den Hollander, Sascha Fauser, John R. W. Yates, Rando Allikmets, Jie Jin Wang, Debra A. Schaumberg, Barbara E. K. Klein, Stephanie A. Hagstrom, Itay Chowers, Andrew J. Lotery, Thierry Léveillard, Kang Zhang, Murray H. Brilliant, Alex W. Hewitt, Anand Swaroop, Emily Y. Chew, Margaret A. Pericak-Vance, Margaret DeAngelis, Dwight Stambolian, Jonathan L. Haines, Sudha K. Iyengar, Bernhard H. F. Weber, Gonçalo R. Abecasis, Iris M. Heid, Tamer Hadi, Matthew D. Anger, Amy Stockwell, Ronald B. Melles, Jie Yin, Hélène Choquet, Rebecca Kaye, Karina Patasova, Praveen J. Patel, Brian L. Yaspan, Eric Jorgenson, Pirro G. Hysi, Andrew J. Lotery, J. Michael Gaziano, Philip S. Tsao, Steven J. Fliesler, Jack M. Sullivan, Paul B. Greenberg, Wen-Chih Wu, Themistocles L. Assimes, Saiju Pyarajan, Panos Roussos, Neal S. Peachey, Sudha K. Iyengar. Genome-wide association analyses identify distinct genetic architectures for age-related macular degeneration across ancestries. Nature Genetics, 2024; 56 (12): 2659 DOI: 10.1038/s41588-024-01764-0
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