ArticleNature genetics2024
Genome-wide association analyses identify distinct genetic architectures for age-related macular degeneration across ancestries.
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Article in Nature genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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29citing papers in PubMed, 1 pooled it
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genetic determinants of age-related macular degeneration in Middle Eastern populations: a systematic review.Frontiers in genetics · 2026Pooled it
- Association of baseline brain care score with the incidence of age-related eye diseases.Eye (London, England) · 2026Article
- A multi-ancestry genome-wide association study of dry eye disease and systemic comorbidities.EBioMedicine · 2026Article
- Genetic evidence and cross-species functional characterization implicateProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Systematic Analysis of Plasma-Derived Extracellular Vesicle-Enriched Samples in Age-Related Macular Degeneration Reveals Oxidative Stress Linked to Altered Lipid and Protein Profiles.Journal of extracellular biology · 2026Article
- Revisiting retinal and macular degeneration in the genomics era.Nature reviews. Genetics · 2026Review
- TLS-Tractor: A transfer learning framework for incorporating summary-statistics into local ancestry-aware GWAS in admixed populations.medRxiv : the preprint server for health sciences · 2026Article
- Interactions Between Epidermal Growth Factor-Containing Fibulin-Like Extracellular Matrix Protein 1 and Tissue Inhibitor of Metalloproteinases-3 and Relevance to Age-Related Macular Degeneration.Ophthalmology science · 2026Review
- An Integrated Multi-omics Single Cell Atlas of the Human RPE and Choroid.bioRxiv : the preprint server for biology · 2026Article
- Paired DNA and RNA sequencing uncovers common and rare variation regulating human retinal gene expression.Nature communications · 2026Article
- Replication of the Association between Retinal Aging Clock Susceptibility Genes and Retinal Age Gap in an Asian Population: The Nagahama Study.Ophthalmology science · 2026Article
- Genetic Evidence for Causal Effects of Blood Metabolites on Age-Related Macular Degeneration and its Subtypes.Translational vision science & technology · 2026Article
- Functional polymorphisms in pigmentation-related genesBiochemistry and biophysics reports · 2026Article
- Age-related macular degeneration and cerebral amyloid angiopathy have similar pathologies from cholesterol-APOE-amyloid-β-complement mediated inflammation.Progress in retinal and eye research · 2026Review
- Air pollutants, genetic susceptibility, and the risk of age-related macular degeneration: a large prospective cohort study.European journal of epidemiology · 2026Article
- Review
- The Evolving Burden of Age-Related Macular Degeneration in China (1990-2023): Insights from an Aging Society and the Anti-VEGF Era.Clinical epidemiology · 2026Article
- A new perspective on AMD pathogenesis: a sequential Factor H-centered view of complement dysregulation.Frontiers in immunology · 2026Review
- Diverse-Ancestry GWAS of Age-Related Macular Degeneration on 16,108 Examined Cases and 18,038 Controls.Investigative ophthalmology & visual science · 2025Article
- Integrative Multiomics Identifies CD64⁺ Monocytes as Potential Contributors to Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2025Article
Corrections and comments
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Authors and funding
40 authors.
Bryan R Gorman *Center for Data and Computational Sciences (C-DACS), VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4239-4672
Georgios Voloudakis *Center for Disease Neurogenomics, Department of Psychiatry; Friedman Brain Institute; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-5729-632X
Robert P Igo *Research Service, VA Northeast Ohio Healthcare System, Cleveland, OH, USA.ORCID http://orcid.org/0000-0002-0024-1993
Tyler KinzyResearch Service, VA Northeast Ohio Healthcare System, Cleveland, OH, USA.
Christopher W HalladayCenter of Innovation in Long Term Services and Supports, VA Providence Healthcare System, Providence, RI, USA.
Tim B BigdeliResearch Service, VA New York Harbor Healthcare System, Brooklyn, NY, USA.
Biao ZengCenter for Disease Neurogenomics, Department of Psychiatry; Friedman Brain Institute; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Sanan VenkateshCenter for Disease Neurogenomics, Department of Psychiatry; Friedman Brain Institute; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Jessica N Cooke BaileyResearch Service, VA Northeast Ohio Healthcare System, Cleveland, OH, USA.ORCID http://orcid.org/0000-0002-4001-8702
Dana C CrawfordResearch Service, VA Northeast Ohio Healthcare System, Cleveland, OH, USA.ORCID http://orcid.org/0000-0002-6437-6248
Kyriacos MarkianosCenter for Data and Computational Sciences (C-DACS), VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA, USA.ORCID http://orcid.org/0000-0003-0214-6014
Frederick DongCenter for Data and Computational Sciences (C-DACS), VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA, USA.
Patrick A SchreinerCenter for Data and Computational Sciences (C-DACS), VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA, USA.ORCID http://orcid.org/0000-0001-5391-2642
Wen ZhangCenter for Disease Neurogenomics, Department of Psychiatry; Friedman Brain Institute; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
VA Million Veteran Program
International AMD Genomics Consortium (IAMDGC)
Tamer HadiEye Clinic, VA Northeast Ohio Healthcare System, Cleveland, OH, USA.
Matthew D AngerEye Clinic, VA Western NY Healthcare System, Buffalo, NY, USA.
Amy StockwellDepartment of Human Genetics, Genentech, South San Francisco, CA, USA.
Ronald B MellesDepartment of Ophthalmology, Kaiser Permanente Northern California, Redwood City, CA, USA.
Jie YinDivision of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
Hélène ChoquetDivision of Research, Kaiser Permanente Northern California, Oakland, CA, USA.ORCID http://orcid.org/0000-0001-9839-8667
Rebecca KayeSouthampton Eye Unit, University Hospital Southampton National Health Service Foundation Trust, Southampton, UK.ORCID http://orcid.org/0000-0002-1504-3201
Karina PatasovaSection of Ophthalmology, School of Life Course Sciences, King's College London, London, UK.
Praveen J PatelNational Institute for Health and Care Research Biomedical Research Centre, Moorfields Eye Hospital National Health Service Foundation Trust, London, UK.ORCID http://orcid.org/0000-0001-8682-4067
Brian L YaspanDepartment of Human Genetics, Genentech, South San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-3787-2510
Eric JorgensonRegeneron Genetics Center, Tarrytown, NY, USA.ORCID http://orcid.org/0000-0002-5829-8191
Pirro G HysiSection of Ophthalmology, School of Life Course Sciences, King's College London, London, UK.ORCID http://orcid.org/0000-0001-5752-2510
Andrew J LoterySouthampton Eye Unit, University Hospital Southampton National Health Service Foundation Trust, Southampton, UK.ORCID http://orcid.org/0000-0001-5541-4305
J Michael GazianoMillion Veteran Program Coordinating Center, VA Boston Healthcare System, Boston, MA, USA.
Philip S TsaoVA Palo Alto Epidemiology Research and Information Center for Genomics, VA Palo Alto Health Care System, Palo Alto, CA, USA.
Steven J FlieslerOphthalmology, Jacobs School of Medicine and Biomedical Sciences, SUNY-University at Buffalo, Buffalo, NY, USA.
Jack M SullivanOphthalmology, Jacobs School of Medicine and Biomedical Sciences, SUNY-University at Buffalo, Buffalo, NY, USA.
Paul B GreenbergSection of Ophthalmology, VA Providence Healthcare System, Providence, RI, USA.
Wen-Chih WuSection of Cardiology, Medical Service, VA Providence Healthcare System, Providence, RI, USA.ORCID http://orcid.org/0000-0002-2834-2024
Themistocles L AssimesVA Palo Alto Epidemiology Research and Information Center for Genomics, VA Palo Alto Health Care System, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0003-2349-0009
Saiju PyarajanCenter for Data and Computational Sciences (C-DACS), VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9047-3762
Panos RoussosCenter for Disease Neurogenomics, Department of Psychiatry; Friedman Brain Institute; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. panagiotis.roussos@mssm.edu.ORCID http://orcid.org/0000-0002-4640-6239
Neal S PeacheyResearch Service, VA Northeast Ohio Healthcare System, Cleveland, OH, USA. neal.peachey@va.gov.ORCID http://orcid.org/0000-0002-4419-7226
Sudha K IyengarResearch Service, VA Northeast Ohio Healthcare System, Cleveland, OH, USA. ski@case.edu.ORCID http://orcid.org/0000-0001-7488-250X
Funding
Clinical and Translational Science Collaborative of ClevelandUL1TR002548 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI MCCOMSEY, GRACE A · 2018 to 2022
$35.5MA Resource for Genetic Epidemiology Research in Adult Health and AgingRC2AG036607 · NIA · KAISER FOUNDATION RESEARCH INSTITUTE · PI RISCH, NEIL J., SCHAEFER, CATHERINE ANN · 2009 to 2010
$24.8MTISSUE CULTURE AND HYBRIDOMA MODULEP30EY011373 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Irina A Pikuleva · 1997 to 2026
$17.7MUnderstanding the molecular mechanisms that contribute to neuropsychiatric symptoms in Alzheimer DiseaseR01AG067025 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FINKBEINER, STEVEN M, HAROUTUNIAN, VAHRAM · 2019 to 2023
$11.8MHigher Order Chromatin and Genetic Risk for Alzheimer's DiseaseR01AG050986 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ROUSSOS, PANAGIOTIS · 2015 to 2025
$11.2MUnderstanding the protective and neuroinflammatory role of human brain immune cells in Alzheimer DiseaseR01AG065582 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAROUTUNIAN, VAHRAM, ROUSSOS, PANAGIOTIS · 2020 to 2024
$9.9MGenetic Variation in Age-Related Macular DegenerationR01EY013435 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ALLIKMETS, RANDO L · 2001 to 2014
$7.7MRESOURCE/SERVICE CORE C - MOLECULAR INFORMATICS MODULEP30EY025585 · NEI · CLEVELAND CLINIC LERNER COM-CWRU · PI BELA ANAND-APTE · 2016 to 2026
$7.7MThe 3D genome in transcriptional regulation across the postnatal life span, with implications for schizophrenia and bipolar disorderU01MH116442 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, DRACHEVA, STELLA · 2018 to 2022
$5.9MMultiethnic genomic epigenomic and transcriptomic fine-mapping and functional validation analysis of schizophrenia and bipolar disorder risk lociR01MH125246 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ROUSSOS, PANAGIOTIS · 2021 to 2025
$5.0MInternational Advancing genomics through the AMD Genomics Consortium (IAMDGC)R01EY022310 · NEI · VANDERBILT UNIVERSITY · PI BLANTON, SUSAN HALLORAN, HAINES, JONATHAN L · 2012 to 2024
$4.9MISOPRENOID METABOLISM IN THE RETINAR01EY007361 · NEI · UNIVERSITY OF SOUTH FLORIDA · PI FLIESLER, STEVEN J. · 1988 to 2015
$4.4MBiomedical Laboratory Research and Development, VA Office of Research and Development (VA Biomedical Laboratory Research and Development) I01BX003364Biomedical Laboratory Research and Development, VA Office of Research and Development (VA Biomedical Laboratory Research and Development) I01BX004189Biomedical Laboratory Research and Development, VA Office of Research and Development (VA Biomedical Laboratory Research and Development) IK6BX005233BLRD VA I01 BX003364BLRD VA I01 BX004189BLRD VA I01 BX004557BLRD VA IK6 BX005233BLRD VA IK6 BX005787NCATS NIH HHS UL1 TR002548NEI NIH HHS P30 EY011373NEI NIH HHS P30 EY025585NEI NIH HHS R01 EY007361NEI NIH HHS R01 EY013435NEI NIH HHS R01 EY022310NEI NIH HHS R01 EY027004NEI NIH HHS R01 EY028203NEI NIH HHS R01 EY029315NEI NIH HHS R01 EY033298NIA NIH HHS R01 AG050986NIA NIH HHS R01 AG065582NIA NIH HHS R01 AG067025NIA NIH HHS RC2 AG036607NIMH NIH HHS K08 MH122911NIMH NIH HHS R01 MH125246NIMH NIH HHS U01 MH116442Research to Prevent Blindness (RPB) I01BX004557
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.
Indexed as
Genetic Predisposition to DiseaseGenome-Wide Association StudyMacular DegenerationPolymorphism, Single NucleotideAgedBlack PeopleComplement Factor HFemaleHaplotypesHigh-Temperature Requirement A Serine Peptidase 1Hispanic or LatinoHumansMaleProteinsComplement Factor HHigh-Temperature Requirement A Serine Peptidase 1Proteins
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