Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry

Autor(es):Mostrar menos -

Hauser, Michael A. ^{[1, 2, 3, 4]} ; Allingham, R. Rand ^{[2, 3, 4]} ; Aung, Tin ^{[3, 4, 5, 6]} ; Van Der Heide, Carly J. ^[7] ; Taylor, Kent D. ^{[8, 9]} ; Rotter, Jerome I. ^[8] ; Wang, Shih-Hsiu J. ^[10] ; Bonnemaijer, Pieter W. M. ^{[11, 12, 13]} ; Williams, Susan E. ^[14] ; Abdullahi, Sadiq M. ^[15] ; Abu-Amero, Khaled K. ^[16] ; Anderson, Michael G. ^[7] ; Akafo, Stephen ^[17] ; Alhassan, Mahmoud B. ^[15] ; Asimadu, Ifeoma ^[18] ; Ayyagari, Radha ^[19] ; Bakayoko, Saydou ^{[20, 21]} ; Nyamsi, Prisca Biangoup ^[22] ; Bowden, Donald W. ^[23] ; Bromley, William C. ^[24] ; Budenz, Donald L. ^[25] ; Carmichael, Trevor R. ^[14] ; Challa, Pratap ^[2] ; Chen, Yii-Der Ida ^{[8, 9]} ; Chuka-Okosa, Chimdi M. ^[26] ; Bailey, Jessica N. Cooke ^{[27, 28]} ; Costa, Vital Paulino ^[29] ; Cruz, Dianne A. ^[30] ; DuBiner, Harvey ^[31] ; Ervin, John F. ^[32] ; Feldman, Robert M. ^[33] ; Flamme-Wiese, Miles ^[7] ; Gaasterland, Douglas E. ^[34] ; Garnai, Sarah J. ^[35] ; Girkin, Christopher A. ^[36] ; Guirou, Nouhoum ^{[20, 21]} ; Guo, Xiuqing ^[8] ; Haines, Jonathan L. ^{[27, 28]} ; Hammond, Christopher J. ^[37] ; Herndon, Leon ^[2] ; Hoffmann, Thomas J. ^{[38, 39]} ; Hulette, Christine M. ^[10] ; Hydara, Abba ^[40] ; Igo, Jr., Robert P. ^[27] ; Jorgenson, Eric ^[41] ; Kabwe, Joyce ^[42] ; Kilangalanga, Ngoy Janvier ^[42] ; Kizor-Akaraiwe, Nkiru ^{[18, 43]} ; Kuchtey, Rachel W. ^[44] ; Lamari, Hasnaa ^[45] ; Li, Zheng ^[46] ; Liebmann, Jeffrey M. ^[47] ; Liu, Yutao ^{[48, 49, 50]} ; Loos, Ruth J. F. ^{[51, 52]} ; Melo, Monica B. ^[53] ; Moroi, Sayoko E. ^[35] ; Msosa, Joseph M. ^[54] ; Mullins, Robert F. ^[7] ; Nadkarni, Girish ^{[51, 55]} ; Napo, Abdoulaye ^{[20, 21]} ; Ng, Maggie C. Y. ^[23] ; Nunes, Hugo Freire ^[53] ; Obeng-Nyarkoh, Ebenezer ^[24] ; Okeke, Anthony ^[56] ; Okeke, Suhanya ^{[18, 43]} ; Olaniyi, Olusegun ^[15] ; Olawoye, Olusola ^[57] ; Oliveira, Mariana Borges ^[53] ; Pasquale, Louise R. ^{[58, 59]} ; Perez-Grossmann, Rodolfo A. ^[60] ; Pericak-Vance, Margaret A. ^[61] ; Qin, Xue ^[62] ; Ramsay, Michele ^[63] ; Resnikoff, Serge ^{[64, 65]} ; Richards, Julia E. ^{[66, 35]} ; Schimiti, Rui Barroso ^[67] ; Sim, Kar Seng ^[46] ; Sponsel, William E. ^{[68, 69]} ; Svidnicki, Paulo Vinicius ^[53] ; Thiadens, Alberta A. H. J. ^{[11, 12]} ; Uche, Nkechinyere J. ^{[26, 43]} ; van Duijn, Cornelia M. ^{[11, 70]} ; Cabral de Vasconcellos, Jose Paulo ^[29] ; Wiggs, Janey L. ^{[71, 72]} ; Zangwill, Linda M. ^[19] ; Risch, Neil ^{[38, 41, 39]} ; Milea, Dan ^{[3, 4, 5]} ; Ashaye, Adeyinka ^[57] ; Klaver, Caroline C. W. ^{[11, 12, 73]} ; Weinreb, Robert N. ^[19] ; Koch, Allison E. Ashley ^[1] ; Fingert, John H. ^[7] ; Khor, Chiea Chuen ^{[46, 3]} ; African, Genetics Glaucoma People

Afiliação do(s) autor(es):Mostrar menos -

^[1] Duke Univ, Dept Med, Durham, NC - USA

^[2] Duke Univ, Dept Ophthalmol, Durham, NC - USA

^[3] Singapore Eye Res Inst, Singapore - Singapore

^[4] Duke NUS Med Sch, Singapore - Singapore

^[5] Singapore Natl Eye Ctr, Singapore - Singapore

^[6] Young Loo Lin Sch Med, Dept Ophthalmol, Singapore - Singapore

^[7] Univ Iowa, Dept Ophthalmol & Visual Sci, Carver Coll Med, Iowa City, IA - USA

^[8] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 - USA

^[9] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 - USA

^[10] Duke Univ, Dept Pathol, Durham, NC 27706 - USA

^[11] Erasmus MC, Dept Epidemiol, Rotterdam - Netherlands

^[12] Erasmus MC, Dept Ophthalmol, Rotterdam - Netherlands

^[13] Rotterdam Eye Hosp, Rotterdam - Netherlands

^[14] Univ Witwatersrand, Dept Neurosci, Div Ophthalmol, Johannesburg - South Africa

^[15] Natl Eye Ctr, Kaduna - Nigeria

^[16] King Saud Univ, Coll Med, Dept Ophthalmol, Riyadh - Saudi Arabia

^[17] Univ Ghana, Med Sch, Dept Surg, Unit Ophthalmol, Accra - Ghana

^[18] ESUT Teaching Hosp Parklane, Dept Ophthalmol, Enugu - Nigeria

^[19] Univ Calif San Diego, Dept Ophthalmol, Hamilton Glaucoma Ctr, Shiley Eye Inst, La Jolla, CA 92093 - USA

^[20] Inst Ophtalmol Trop Afrique, Bamako - Mali

^[21] Univ Sci Tech & Technol Bamako, Bamako - Mali

^[22] Hop Militaire Reg 1 Yaounde, Serv Specialise Ophtalmol, Yaounde - Cameroon

^[23] Wake Forest Sch Med, Dept Biochem, Ctr Diabet Res, Winston Salem, NC 27101 - USA

^[24] Ctr Human Genet, Bar Harbor, ME - USA

^[25] Univ N Carolina, Dept Ophthalmol, Chapel Hill, NC 27515 - USA

^[26] Univ Nigeria, Teaching Hosp, Enugu - Nigeria

^[27] Case Western Reserve Univ, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 - USA

^[28] Case Western Reserve Univ, Inst Computat Biol, Cleveland, OH 44106 - USA

^[29] Univ Estadual Campinas, Fac Med Sci, Dept Ophthalmol, Campinas, SP - Brazil

^[30] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC - USA

^[31] Clayton Eye Care Ctr Management Inc, Marrow, GA - USA

^[32] Duke Univ, Dept Neurol, Kathleen Price Bryan Brain Bank & Biorepository, Durham, NC - USA

^[33] Univ Texas Hlth Sci Ctr Houston, Ruiz Dept Ophthalmol & Visual Sci, McGovern Med Sch, Houston, TX 77030 - USA

^[34] Emmes Corp, Rockville, MD - USA

^[35] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 - USA

^[36] Univ Alabama Birmingham, Dept Ophthalmol & Visual Sci, Birmingham, AL - USA

^[37] Kings Coll London, FoLSM, Sch Life Course Sci, Sect Acad Ophthalmol, London - England

^[38] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 - USA

^[39] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 - USA

^[40] Sheikh Zayed Reg Eye Care Ctr, Kanifing - Gambia

^[41] Kaiser Permanente Northern Calif, Div Res, Oakland, CA - USA

^[42] St Joseph Hosp, Dept Ophthalmol, Kinshasa, Limete - DEM REP CONGO

^[43] Eye Specialists Hosp, Enugu - Nigeria

^[44] Vanderbilt Univ, Med Ctr, Dept Ophthalmol & Visual Sci, Nashville, TN - USA

^[45] Clin Specialisee Ophtalmol Mohammedia, Mohammadia - Morocco

^[46] Genome Inst Singapore, Singapore - Singapore

^[47] Columbia Univ, Med Ctr, Harkness Eye Inst, Bernard & Shirlee Brown Glaucoma Res Lab, New York, NY - USA

^[48] Augusta Univ, Cellular Biol & Anat, Augusta, GA - USA

^[49] Augusta Univ, James & Jean Culver Vis Discovery Inst, Augusta, GA - USA

^[50] Augusta Univ, Ctr Biotechnol & Genom Med, Augusta, GA - USA

^[51] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 - USA

^[52] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 - USA

^[53] Univ Estadual Campinas, Ctr Mol Biol & Genet Engn, Campinas, SP - Brazil

^[54] Kamuzu Cent Hosp, Lions Sight Eye Hosp 1, Lilongwe - Malawi

^[55] Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 - USA

^[56] Nigerian Navy Reference Hosp, Lagos - Nigeria

^[57] Univ Ibadan, Dept Ophthalmol, Ibadan - Nigeria

^[58] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 - USA

^[59] Icahn Sch Med Mt Sinai, Dept Ophthalmol, New York, NY - USA

^[60] Inst Glaucoma & Catarata, Lima - Peru

^[61] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 - USA

^[62] Duke Univ, Duke Mol Physiol Inst, Durham, NC - USA

^[63] Univ Witwatersrand, Fac Hlth Sci, Sydney Brenner Inst Mol Biosci, Johannesburg - South Africa

^[64] Brien Holden Vis Inst, Sydney, NSW - Australia

^[65] Univ New South Wales, Sch Optometry & Vis Sci, Sydney, NSW - Australia

^[66] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 - USA

^[67] Hoftalon Hosp, Londrina, Parana - Brazil

^[68] San Antonio Eye Hlth, San Antonio, TX - USA

^[69] Child Legacy Int CLI Hosp, Eyes Africa, Msundwe - Malawi

^[70] Univ Oxford, Nuffield Dept Publ Hlth, Oxford - England

^[71] Harvard Univ, Med Sch, Boston, MA 02115 - USA

^[72] Massachusetts Eye & Ear Infirm, Boston, MA - USA

^[73] Radboud Univ Nijmegen, Med Ctr, Dept Ophthalmol, Nijmegen - Netherlands

• Tipo de documento: Artigo Científico
• Fonte: JAMA; v. 322, n. 17, p. 1682-1691, NOV 5 2019.
• Citações Web of Science: 1

Resumo

Key PointsQuestionAre there differences in genetic risk factors for primary open-angle glaucoma based on ancestry? FindingsIn this multistage, case-control, genome-wide association study that included 26295 participants, the amyloid-beta A4 precursor protein-binding family B member 2 (APBB2) locus was significantly associated with primary open-angle glaucoma among individuals of African ancestry (odds ratio, 1.19 per copy of the risk allele for single-nucleotide polymorphism rs59892895T>C), but not of European or Asian ancestry. MeaningThis study identified a single-nucleotide polymorphism that demonstrated differential association with primary open-angle glaucoma by ancestry. ImportancePrimary 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. ObjectivesTo 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. Design, Settings, and ParticipantsA 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 14917 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. ExposuresGenetic variants associated with primary open-angle glaucoma. Main Outcomes and MeasuresPresence of primary open-angle glaucoma. Genome-wide significance was defined as P<5x10(-8) in the discovery stage and in the meta-analysis of combined discovery and validation data. ResultsA 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-beta 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=2x10(-8)). The association was validated in an analysis of an additional 6937 affected individuals and 14917 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=4x10(-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. Conclusions and RelevanceIn 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. This genome-wide association study (GWAS) investigates genetic loci associated with primary open-angle glaucoma in individuals in Africa and in the United States with African ancestry. (AU)

• Processo FAPESP: 02/11575-0 - Identificação de genes associados ao glaucoma primário de ângulo aberto
• Beneficiário: José Paulo Cabral de Vasconcellos
• Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
• Processo FAPESP: 10/18353-9 - Citocinas inflamatórias e associação com o tratamento e etiologia do glaucoma primário de ângulo aberto
• Beneficiário: Mônica Barbosa de Melo
• Linha de fomento: Auxílio à Pesquisa - Regular