Journal article
Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry
JAMA : the journal of the American Medical Association, Vol.322(17), pp.1682-1691
11/05/2019
DOI: 10.1001/jama.2019.16161
PMCID: PMC6865235
PMID: 31688885
Abstract
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.
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.
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.
Genetic variants associated with primary open-angle glaucoma.
Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data.
A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>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 < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry.
In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies.
Details
- Title: Subtitle
- Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry
- Creators
- Michael A Hauser - Duke-NUS Medical School, SignaporeR Rand Allingham - Duke-NUS Medical School, SignaporeTin Aung - Department of Ophthalmology, Young Loo Lin School of Medicine, SingaporeCarly J Van Der Heide - Carver College of Medicine, Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa CityKent D Taylor - Department of Pediatrics, Harbor-University of California, Los Angeles Medical Center, TorranceJerome I Rotter - The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CaliforniaShih-Hsiu J Wang - Department of Pathology, Duke University, Durham, North CarolinaPieter W M Bonnemaijer - Department of Ophthalmology, Erasmus MC, Rotterdam, the NetherlandsSusan E Williams - Division of Ophthalmology, Department of Neurosciences, University of the Witwatersrand, Johannesburg, South AfricaSadiq M Abdullahi - National Eye Centre, Kaduna, NigeriaKhaled K Abu-Amero - Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi ArabiaMichael G Anderson - Carver College of Medicine, Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa CityStephen Akafo - Unit of Ophthalmology, Department of Surgery, University of Ghana Medical School, Accra, GhanaMahmoud B Alhassan - National Eye Centre, Kaduna, NigeriaIfeoma Asimadu - Department of Ophthalmology, ESUT Teaching Hospital Parklane, Enugu, NigeriaRadha Ayyagari - Shiley Eye Institute, Hamilton Glaucoma Center, Department of Ophthalmology, University of California, San Diego, La JollaSaydou Bakayoko - Université des Sciences des Techniques et des Technologies de Bamako, Bamako, MaliPrisca Biangoup Nyamsi - Service Spécialisé d'ophtalmologie, Hôpital Militaire de Région No1 de Yaoundé, Yaoundé, CamerounDonald W Bowden - Center for Diabetes Research, Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North CarolinaWilliam C Bromley - Center for Human Genetics, Bar Harbor, MaineDonald L Budenz - Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, North CarolinaTrevor R Carmichael - Division of Ophthalmology, Department of Neurosciences, University of the Witwatersrand, Johannesburg, South AfricaPratap Challa - Department of Ophthalmology, Duke University, Durham, North CarolinaYii-Der Ida Chen - Department of Pediatrics, Harbor-University of California, Los Angeles Medical Center, TorranceChimdi M Chuka-Okosa - University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu, NigeriaJessica N Cooke Bailey - Institute for Computational Biology, Case Western Reserve University, Cleveland, OhioVital Paulino Costa - Department of Ophthalmology, Faculty of Medical Sciences, University of Campinas, Campinas, BrazilDianne A Cruz - Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North CarolinaHarvey DuBiner - Clayton Eye Care Center Management Inc, Marrow, GeorgiaJohn F Ervin - Kathleen Price Bryan Brain Bank and Biorepository, Department of Neurology, Duke University, Durham, North CarolinaRobert M Feldman - McGovern Medical School, Ruiz Department of Ophthalmology & Visual Science, The University of Texas Health Science Center at Houston, HoustonMiles Flamme-Wiese - Carver College of Medicine, Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa CityDouglas E Gaasterland - The Emmes Corporation, Rockville, MarylandSarah J Garnai - Department of Ophthalmology and Visual Sciences, University of Michigan, Ann ArborChristopher A Girkin - Department of Ophthalmology and Visual Sciences, University of Alabama at BirminghamNouhoum Guirou - Université des Sciences des Techniques et des Technologies de Bamako, Bamako, MaliXiuqing Guo - The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CaliforniaJonathan L Haines - Institute for Computational Biology, Case Western Reserve University, Cleveland, OhioChristopher J Hammond - Section of Academic Ophthalmology, School of Life Course Sciences, FoLSM, King's College London, London, United KingdomLeon Herndon - Department of Ophthalmology, Duke University, Durham, North CarolinaThomas J Hoffmann - Institute for Human Genetics, University of California at San FranciscoChristine M Hulette - Department of Pathology, Duke University, Durham, North CarolinaAbba Hydara - Sheikh Zayed Regional Eye Care Centre, Kanifing, The GambiaRobert P Igo Jr - Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OhioEric Jorgenson - Division of Research, Kaiser Permanente Northern California, OaklandJoyce Kabwe - Department of Ophthalmology, St Joseph Hospital, Kinshasa, Limete, Democratic Republic of the CongoNgoy Janvier Kilangalanga - Department of Ophthalmology, St Joseph Hospital, Kinshasa, Limete, Democratic Republic of the CongoNkiru Kizor-Akaraiwe - The Eye Specialists Hospital, Enugu, NigeriaRachel W Kuchtey - Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TennesseeHasnaa Lamari - Clinique Spécialisée en Ophtalmologie Mohammedia, Mohammedia, MoroccoZheng Li - Genome Institute of Singapore, SingaporeJeffrey M Liebmann - Bernard and Shirlee Brown Glaucoma Research Laboratory, Harkness Eye Institute, Columbia University Medical Center, New York, New YorkYutao Liu - Center for Biotechnology & Genomic Medicine, Augusta University, Augusta, GeorgiaRuth J F Loos - The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New YorkMonica B Melo - Center for Molecular Biology and Genetic Engineering, University of Campinas, Campinas, BrazilSayoko E Moroi - Department of Ophthalmology and Visual Sciences, University of Michigan, Ann ArborJoseph M Msosa - Lions Sight-First Eye Hospital, Kamuzu Central Hospital, Lilongwe, MalawiRobert F Mullins - Carver College of Medicine, Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa CityGirish Nadkarni - Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New YorkAbdoulaye Napo - Université des Sciences des Techniques et des Technologies de Bamako, Bamako, MaliMaggie C Y Ng - Center for Diabetes Research, Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North CarolinaHugo Freire Nunes - Center for Molecular Biology and Genetic Engineering, University of Campinas, Campinas, BrazilEbenezer Obeng-Nyarkoh - Center for Human Genetics, Bar Harbor, MaineAnthony Okeke - Nigerian Navy Reference Hospital, Ojo, Lagos, NigeriaSuhanya Okeke - The Eye Specialists Hospital, Enugu, NigeriaOlusegun Olaniyi - National Eye Centre, Kaduna, NigeriaOlusola Olawoye - Department of Ophthalmology, University of Ibadan, Ibadan, NigeriaMariana Borges Oliveira - Center for Molecular Biology and Genetic Engineering, University of Campinas, Campinas, BrazilLouise R Pasquale - Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MassachusettsRodolfo A Perez-Grossmann - Instituto de Glaucoma y Catarata, Lima, PeruMargaret A Pericak-Vance - John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FloridaXue Qin - Duke Molecular Physiology Institute, Duke University, Durham, North CarolinaMichele Ramsay - Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaSerge Resnikoff - School of Optometry and Vision Science, University of New South Wales, Sydney, AustraliaJulia E Richards - Department of Epidemiology, University of Michigan, Ann ArborRui Barroso Schimiti - Hoftalon Hospital, Londrina, BrazilKar Seng Sim - Genome Institute of Singapore, SingaporeWilliam E Sponsel - Eyes of Africa, Child Legacy International (CLI) Hospital, Msundwe, MalawiPaulo Vinicius Svidnicki - Center for Molecular Biology and Genetic Engineering, University of Campinas, Campinas, BrazilAlberta A H J Thiadens - Department of Ophthalmology, Erasmus MC, Rotterdam, the NetherlandsNkechinyere J Uche - The Eye Specialists Hospital, Enugu, NigeriaCornelia M van Duijn - Nuffield Department of Public Health, University of Oxford, Oxford, United KingdomJosé Paulo Cabral de Vasconcellos - Department of Ophthalmology, Faculty of Medical Sciences, University of Campinas, Campinas, BrazilJaney L Wiggs - Massachusetts Eye and Ear Hospital, BostonLinda M Zangwill - Shiley Eye Institute, Hamilton Glaucoma Center, Department of Ophthalmology, University of California, San Diego, La JollaNeil Risch - Division of Research, Kaiser Permanente Northern California, OaklandDan Milea - Singapore National Eye Center, SingaporeAdeyinka Ashaye - Department of Ophthalmology, University of Ibadan, Ibadan, NigeriaCaroline C W Klaver - Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the NetherlandsRobert N Weinreb - Shiley Eye Institute, Hamilton Glaucoma Center, Department of Ophthalmology, University of California, San Diego, La JollaAllison E Ashley Koch - Department of Medicine, Duke University, Durham, North CarolinaJohn H Fingert - Carver College of Medicine, Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa CityChiea Chuen Khor - Genome Institute of Singapore, SingaporeGenetics of Glaucoma in People of African Descent (GGLAD) Consortium
- Resource Type
- Journal article
- Publication Details
- JAMA : the journal of the American Medical Association, Vol.322(17), pp.1682-1691
- DOI
- 10.1001/jama.2019.16161
- PMID
- 31688885
- PMCID
- PMC6865235
- ISSN
- 0098-7484
- eISSN
- 1538-3598
- Grant note
- P30 AG028377 / NIA NIH HHS R01 EY019869 / NEI NIH HHS P30 EY014104 / NEI NIH HHS T32 GM007337 / NIGMS NIH HHS UL1 TR001881 / NCATS NIH HHS U54 HG009826 / NHGRI NIH HHS I01 RX001481 / RRD VA R01 EY023512 / NEI NIH HHS R01 DK110113 / NIDDK NIH HHS R01 DK107786 / NIDDK NIH HHS R01 EY010008 / NEI NIH HHS R01 DK087914 / NIDDK NIH HHS R01 EY021818 / NEI NIH HHS R01 EY022305 / NEI NIH HHS R01 EY015473 / NEI NIH HHS R21 EY028671 / NEI NIH HHS R01 DK053591 / NIDDK NIH HHS R01 DK066358 / NIDDK NIH HHS U01 DK105556 / NIDDK NIH HHS U01 HG007417 / NHGRI NIH HHS R01 EY027004 / NEI NIH HHS R01 DK101855 / NIDDK NIH HHS R01 EY023704 / NEI NIH HHS U01 HG004728 / NHGRI NIH HHS R01 DK070941 / NIDDK NIH HHS P30 EY022589 / NEI NIH HHS P30 DK063491 / NIDDK NIH HHS
- Language
- English
- Date published
- 11/05/2019
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Ophthalmology and Visual Sciences
- Record Identifier
- 9984172263702771
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