Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries

Autor: 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, Wiggs, Janey L
Přispěvatelé: Epidemiology, Ophthalmology, Clinical Genetics, Gharahkhani, Puya [0000-0002-4203-5952], Jorgenson, Eric [0000-0002-5829-8191], Hysi, Pirro [0000-0001-5752-2510], Khawaja, Anthony P [0000-0001-6802-8585], Han, Xikun [0000-0002-3823-7308], Ong, Jue Sheng [0000-0002-6062-710X], Hewitt, Alex W [0000-0002-5123-5999], Rouhana, John M [0000-0002-8599-0271], Igo, Robert P [0000-0002-0024-1993], Choquet, Helene [0000-0001-9839-8667], Josyula, Navya S [0000-0003-2782-8812], Cooke Bailey, Jessica N [0000-0002-4001-8702], Bonnemaijer, Pieter WM [0000-0001-5154-6765], Iglesias, Adriana [0000-0001-5532-764X], Siggs, Owen M [0000-0003-2840-4851], Young, Terri L [0000-0001-6994-9941], Vitart, Veronique [0000-0002-4991-3797], Thiadens, Alberta AHJ [0000-0002-4911-9462], Luben, Robert [0000-0002-5088-6343], Simcoe, Mark [0000-0003-2432-0810], Cree, Angela J [0000-0002-1987-8900], Poplawski, Alicia [0000-0003-2527-0763], Rong, Shi-Song [0000-0001-8352-6363], Vithana, Eranga Nishanthie [0000-0002-8898-0095], Yamamoto, Masayuki [0000-0002-9073-9436], Currant, Hannah [0000-0003-2764-6787], Birney, Ewan [0000-0001-8314-8497], Wang, Xin [0000-0001-7242-357X], Martin, Nicholas G [0000-0003-4069-8020], Olawoye, Olusola [0000-0003-2357-8924], Williams, Susan E [0000-0002-4479-8638], Ramsay, Michele [0000-0002-4156-4801], Kamatani, Yoichiro [0000-0001-8748-5597], Foster, Paul J [0000-0002-4755-177X], Khaw, Peng T [0000-0002-8087-2268], Kraft, Peter [0000-0002-4472-8103], Kang, Jae H [0000-0003-4812-0557], Pasutto, Francesca [0000-0002-0026-5362], Lotery, Andrew J [0000-0001-5541-4305], Haines, Jonathan L [0000-0002-4351-4728], Hammond, Chris [0000-0002-3227-2620], Pasquale, Louis R [0000-0002-5835-3496], Klaver, Caroline CW [0000-0002-2355-5258], Khor, Chiea Chuen [0000-0002-1128-4729], Cheng, Ching-Yu [0000-0003-0655-885X], MacGregor, Stuart [0000-0001-6731-8142], Wiggs, Janey L [0000-0003-1890-3278], Apollo - University of Cambridge Repository, Institute for Molecular Medicine Finland, Helsinki Institute of Life Science HiLIFE, University of Helsinki, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, HUSLAB, HUS Helsinki and Uusimaa Hospital District, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Neuroinfection & -inflammation
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Aging
genetic structures
General Physics and Astronomy
Glaucoma
PROTEIN
Genome-wide association study
Neurodegenerative
Genome
ANNOTATION
Genome-wide association studies
Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]
0302 clinical medicine
Polymorphism (computer science)
Genotype
2.1 Biological and endogenous factors
ANZRAG consortium
Aetiology
GENE-EXPRESSION
Genetics
HUMAN-DISEASES
RISK
Multidisciplinary
and Me Research Team
Single Nucleotide
ASSOCIATION
GIGA study group
Biobank Japan project
3. Good health
PREVALENCE
Open-Angle
Meta-analysis
NEIGHBORHOOD consortium
Optic nerve diseases
Glaucoma
Open-Angle
Asian Continental Ancestry Group
Open angle glaucoma
Science
European Continental Ancestry Group
FinnGen study
Biology
GENOTYPE IMPUTATION
Polymorphism
Single Nucleotide
General Biochemistry
Genetics and Molecular Biology
UK Biobank Eye and Vision Consortium
Article
White People
03 medical and health sciences
Asian People
medicine
Humans
Genetic Predisposition to Disease
3125 Otorhinolaryngology
ophthalmology
Polymorphism
Eye Disease and Disorders of Vision
Genetic association
MUTATIONS
Human Genome
General Chemistry
medicine.disease
eye diseases
030104 developmental biology
Genetic Loci
DIFFERENTIAL EXPRESSION ANALYSIS
030221 ophthalmology & optometry
sense organs
Genome-Wide Association Study
Zdroj: Nature Communications, 12(1):1258. Nature Publishing Group
NEIGHBORHOOD Consortium, ANZRAG consortium, Biobank Japan project, FinnGen study, UK Biobank Eye and Vision Consortium, GIGA study group & 23 and Me Research Team 2021, ' Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries ', Nature Communications, vol. 12, no. 1, 1258 . https://doi.org/10.1038/s41467-020-20851-4
Nature Communications
Nature communications, vol 12, iss 1
Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021)
Nature Communications, 12
Nature Communications, 12, 1
ISSN: 2041-1723
Popis: 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.
Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.
Databáze: OpenAIRE
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