@article {1474210,
	title = {Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry},
	journal = {JAMA},
	volume = {322},
	number = {17},
	year = {2019},
	month = {2019 11 05},
	pages = {1682-1691},
	abstract = {Importance: 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. Objectives: 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. Design, Settings, and Participants: 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. Exposures: Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures: Presence of primary open-angle glaucoma. Genome-wide significance was defined as P \&lt; 5 {\texttimes} 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results: 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\&gt;C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95\% CI, 1.20-1.46]; P = 2 {\texttimes} 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 \&lt; .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 {\texttimes} 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. Conclusions and Relevance: 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.},
	keywords = {Adaptor Proteins, Signal Transducing, African Continental Ancestry Group, Aged, Amyloid beta-Peptides, Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Glaucoma, Open-Angle, Humans, Immunohistochemistry, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors},
	issn = {1538-3598},
	doi = {10.1001/jama.2019.16161},
	author = {Genetics of Glaucoma in People of African Descent (GGLAD) Consortium and Hauser, Michael A and Allingham, R Rand and Aung, Tin and Van Der Heide, Carly J and Taylor, Kent D and Rotter, Jerome I and Wang, Shih-Hsiu J and Bonnemaijer, Pieter W M and Williams, Susan E and Abdullahi, Sadiq M and Abu-Amero, Khaled K and Anderson, Michael G and Akafo, Stephen and Alhassan, Mahmoud B and Asimadu, Ifeoma and Ayyagari, Radha and Bakayoko, Saydou and Nyamsi, Prisca Biangoup and Bowden, Donald W and Bromley, William C and Budenz, Donald L and Carmichael, Trevor R and Challa, Pratap and Chen, Yii-Der Ida and Chuka-Okosa, Chimdi M and Cooke Bailey, Jessica N and Costa, Vital Paulino and Cruz, Dianne A and DuBiner, Harvey and Ervin, John F and Feldman, Robert M and Flamme-Wiese, Miles and Gaasterland, Douglas E and Garnai, Sarah J and Girkin, Christopher A and Guirou, Nouhoum and Guo, Xiuqing and Haines, Jonathan L and Hammond, Christopher J and Herndon, Leon and Hoffmann, Thomas J and Hulette, Christine M and Hydara, Abba and Igo, Robert P and Jorgenson, Eric and Kabwe, Joyce and Kilangalanga, Ngoy Janvier and Kizor-Akaraiwe, Nkiru and Kuchtey, Rachel W and Lamari, Hasnaa and Li, Zheng and Liebmann, Jeffrey M and Liu, Yutao and Loos, Ruth J F and Melo, Monica B and Moroi, Sayoko E and Msosa, Joseph M and Mullins, Robert F and Nadkarni, Girish and Napo, Abdoulaye and Ng, Maggie C Y and Nunes, Hugo Freire and Obeng-Nyarkoh, Ebenezer and Okeke, Anthony and Okeke, Suhanya and Olaniyi, Olusegun and Olawoye, Olusola and Oliveira, Mariana Borges and Pasquale, Louise R and Perez-Grossmann, Rodolfo A and Pericak-Vance, Margaret A and Qin, Xue and Ramsay, Michele and Resnikoff, Serge and Richards, Julia E and Schimiti, Rui Barroso and Sim, Kar Seng and Sponsel, William E and Svidnicki, Paulo Vinicius and Thiadens, Alberta A H J and Uche, Nkechinyere J and van Duijn, Cornelia M and de Vasconcellos, Jos{\'e} Paulo Cabral and Wiggs, Janey L and Zangwill, Linda M and Risch, Neil and Milea, Dan and Ashaye, Adeyinka and Klaver, Caroline C W and Weinreb, Robert N and Ashley Koch, Allison E and Fingert, John H and Khor, Chiea Chuen}
}
