@article{3c087eb9743d4bbaaf8f3a97ee1fcb8c,
title = "Genome-wide association analyses identify distinct genetic architectures for age-related macular degeneration across ancestries",
abstract = "To effectively reduce vision loss due to age-related macular generation (AMD) on a global scale, knowledge of its genetic architecture in diverse populations is necessary. A critical element, AMD risk profiles in African and Hispanic/Latino ancestries, remains largely unknown. We combined data in the Million Veteran Program with five other cohorts to conduct the first multi-ancestry genome-wide association study of AMD and discovered 63 loci (30 novel). We observe marked cross-ancestry heterogeneity at major risk loci, especially in African-ancestry populations which demonstrate a primary signal in a major histocompatibility complex class II haplotype and reduced risk at the established CFH and ARMS2/HTRA1 loci. Dissecting local ancestry in admixed individuals, we find significantly smaller marginal effect sizes for CFH risk alleles in African ancestry haplotypes. Broadening efforts to include ancestrally distinct populations helped uncover genes and pathways that boost risk in an ancestry-dependent manner and are potential targets for corrective therapies.",
keywords = "Genetics, Population genetics, Macular degeneration",
author = "Gorman, {Bryan R.} and Georgios Voloudakis and Igo, {Robert P.} and Tyler Kinzy and Halladay, {Christopher W.} and Bigdeli, {Tim B.} and Biao Zeng and Sanan Venkatesh and {Cooke Bailey}, {Jessica N.} and Crawford, {Dana C.} and Kyriacos Markianos and Frederick Dong and Schreiner, {Patrick A.} and Wen Zhang and {VA Million Veteran Program} and {International AMD Genomics Consortium (IAMDGC)} and Heid, {Iris M.} and Abecasis, {Gon{\c c}alo R.} and Weber, {Bernhard H.F.} and Iyengar, {Sudha K.} and Haines, {Jonathan L.} and Dwight Stambolian and Margaret DeAngelis and Pericak-Vance, {Margaret A.} and Chew, {Emily Y.} and Anand Swaroop and Hewitt, {Alex W.} and Brilliant, {Murray H.} and Kang Zhang and Thierry L{\'e}veillard and Lotery, {Andrew J.} and Itay Chowers and Hagstrom, {Stephanie A.} and Klein, {Barbara E.K.} and Schaumberg, {Debra A.} and Wang, {Jie Jin} and Rando Allikmets and Yates, {John R.W.} and Sascha Fauser and {den Hollander}, {Anneke I.} and Baird, {Paul N.} and Klein, {Michael L.} and Gorin, {Michael B.} and Caroline Hayward and Klaver, {Caroline C.W.} and Jane Romm and Doheny, {Kimberly F.} and {van Duijn}, {Cornelia M.} and Bal Dhillon and Weeks, {Daniel E.} and John Blangero and Martin, {Tammy M.} and Richardson, {Andrea J.} and Cain, {Melinda S.} and Hoyng, {Carel B.} and deJohn, {Eiko K.} and Saksens, {Nicole T.M.} and Thomas Langmann and Albert Caramoy and Lebriz Ersoy and Anita Agarwal and Brantley, {Milam A.} and Rene{\'e} Laux and McGrath, {J. Allie} and Moore, {Anthony T.} and Humma Shahidi and Khan, {Jane C.} and Smith, {R. Theodore} and Merriam, {John C.} and Bamini Gopinath and Tan, {Ava G.} and Gerald Liew and Scott, {William K.} and Kovach, {Jaclyn L.} and Schwartz, {Stephen G.} and Courtenay, {Monique D.} and Postel, {Eric A.} and Hauser, {Michael A.} and Ronald Klein and Moore, {Emily L.} and Myers, {Chelsea E.} and Meuer, {Stacy M.} and Barbara Truitt and Igo, {Robert P.} and Deleuze, {Jean Fran{\c c}ois} and H{\'e}l{\`e}ne Blanch{\'e} and Fr{\'e}d{\'e}ric Blond and Holz, {Frank G.} and Nicholas Katsanis and Peter Campochiaro and Shira Hagbi-Levi and Michelle Grunin and Goverdhan, {Srinivas V.} and Rennie, {Christina A.} and Cree, {Angela J.} and Mustapha Benchaboune and Isabelle Audo and Sahel, {Jos{\'e} Alain} and Saddek Mohand-Sa{\"i}d and Curcio, {Christine A.} and Mingyao Li and Alexander Brucker and Anton Orlin and Farrer, {Lindsay A.} and Park, {Kyu Hyung} and Tsironi, {Evangelia E.} and Giuliana Silvestri and Jeeyun Ahn and Matthew Schu and Morgan, {Deniste J.} and Morrison, {Margaux A.} and Matthias Olden and Guenther Rudolph and Caroline Brandl and Armin Wolf and Strachwitz, {Claudia Nvon} and Klaus Stark and Henry Ferreyra and Guanping Mao and Daniel Lin and Ken Flagg and Ouyang Ouyang and Daniel Chen and Hongrong Luo and Zhiquang Su and Zhenglin Yang and Terrie Kitchner and Craig, {Jamie E.} and Constable, {Ian J.} and Mackey, {David A.} and Stewart Lake and Janette Hall and Timothy Isaacs and McAllister, {Ian L.} and Emmanuelle Souzeau and Liang, {Helena Hai} and Vote, {Brendan J.} and Othman, {Mohammad I.} and Heckenlively, {John R.} and Foerster, {Johanna R.} and Branham, {Kari E.} and Rinki Ratnapriya and Linn Gieser and Matthew Brooks and Alexis Boleda and Kwong, {Alan M.} and Xiaowei Zhan and Buitendijk, {Gabri{\"e}lle H.S.} and Stanton, {Chloe M.} and Yingda Jiang and Johnson, {Matthew P.} and Guymer, {Robyn H.} and Lechanteur, {Yara T.E.} and Tina Schick and Hoffman, {Joshua D.} and Valentina Cipriani and Merriam, {Joanna E.} and Paul Mitchell and Sardell, {Rebecca J.} and Hunter, {David J.} and Lee, {Kristine E.} and Elisa Bala and Scholl, {Hendrik P.N.} and Eric Souied and Donald Zack and David Cho and Kim, {Ivana K.} and Mathias Gorski and Cindy Wen and Hebring, {Scott J.} and Burdon, {Kathryn P.} and Bragg-Gresham, {Jennifer L.} and Sebanti Sengupta and Felix Grassman and {Cooke Bailey}, {Jessica N.} and Wilmar Igl and Fritsche, {Lars G.} and Tamer Hadi and Anger, {Matthew D.} and Amy Stockwell and Melles, {Ronald B.} and Jie Yin and H{\'e}l{\`e}ne Choquet and Rebecca Kaye and Karina Patasova and Patel, {Praveen J.} and Yaspan, {Brian L.} and Eric Jorgenson and Hysi, {Pirro G.} and Lotery, {Andrew J.} and Gaziano, {J. Michael} and Tsao, {Philip S.} and Fliesler, {Steven J.} and Sullivan, {Jack M.} and Greenberg, {Paul B.} and Wu, {Wen Chih} and Assimes, {Themistocles L.} and Saiju Pyarajan and Panos Roussos and Peachey, {Neal S.} and Iyengar, {Sudha K.}",
year = "2024",
month = dec,
doi = "10.1038/s41588-024-01764-0",
language = "English",
volume = "56",
pages = "2659--2671",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "12",
}