Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry
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 disorder...
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| Veröffentlicht in: | JAMA : the journal of the American Medical Association 2019-11, Vol.322 (17), p.1682-1691 |
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| creator | Hauser, Michael A Allingham, R. Rand Aung, Tin Van Der Heide, Carly J Taylor, Kent D Rotter, Jerome I Wang, Shih-Hsiu J Bonnemaijer, Pieter W. M Williams, Susan E Abdullahi, Sadiq M Abu-Amero, Khaled K Anderson, Michael G Akafo, Stephen Alhassan, Mahmoud B Asimadu, Ifeoma Ayyagari, Radha Bakayoko, Saydou Nyamsi, Prisca Biangoup Bowden, Donald W Bromley, William C Budenz, Donald L Carmichael, Trevor R Challa, Pratap Chen, Yii-Der Ida Chuka-Okosa, Chimdi M Cooke Bailey, Jessica N Costa, Vital Paulino Cruz, Dianne A DuBiner, Harvey Ervin, John F Feldman, Robert M Flamme-Wiese, Miles Gaasterland, Douglas E Garnai, Sarah J Girkin, Christopher A Guirou, Nouhoum Guo, Xiuqing Haines, Jonathan L Hammond, Christopher J Herndon, Leon Hoffmann, Thomas J Hulette, Christine M Hydara, Abba Igo, Robert P Jorgenson, Eric Kabwe, Joyce Kilangalanga, Ngoy Janvier Kizor-Akaraiwe, Nkiru Kuchtey, Rachel W Lamari, Hasnaa Li, Zheng Liebmann, Jeffrey M Liu, Yutao Loos, Ruth J.F Melo, Monica B Moroi, Sayoko E Msosa, Joseph M Mullins, Robert F Nadkarni, Girish Napo, Abdoulaye Ng, Maggie C. Y Nunes, Hugo Freire Obeng-Nyarkoh, Ebenezer Okeke, Anthony Okeke, Suhanya Olaniyi, Olusegun Olawoye, Olusola Oliveira, Mariana Borges Pasquale, Louise R Perez-Grossmann, Rodolfo A Pericak-Vance, Margaret A Qin, Xue Ramsay, Michele Resnikoff, Serge Richards, Julia E Schimiti, Rui Barroso Sim, Kar Seng Sponsel, William E Svidnicki, Paulo Vinicius Thiadens, Alberta A. H. J Uche, Nkechinyere J van Duijn, Cornelia M de Vasconcellos, José Paulo Cabral Wiggs, Janey L Zangwill, Linda M Risch, Neil Milea, Dan Ashaye, Adeyinka Klaver, Caroline C. W Weinreb, Robert N Ashley Koch, Allison E Fingert, John H Khor, Chiea Chuen |
| description | 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 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 |
| doi_str_mv | 10.1001/jama.2019.16161 |
| format | Article |
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Rand ; Aung, Tin ; Van Der Heide, Carly J ; Taylor, Kent D ; Rotter, Jerome I ; Wang, Shih-Hsiu J ; Bonnemaijer, Pieter W. M ; Williams, Susan E ; Abdullahi, Sadiq M ; Abu-Amero, Khaled K ; Anderson, Michael G ; Akafo, Stephen ; Alhassan, Mahmoud B ; Asimadu, Ifeoma ; Ayyagari, Radha ; Bakayoko, Saydou ; Nyamsi, Prisca Biangoup ; Bowden, Donald W ; Bromley, William C ; Budenz, Donald L ; Carmichael, Trevor R ; Challa, Pratap ; Chen, Yii-Der Ida ; Chuka-Okosa, Chimdi M ; Cooke Bailey, Jessica N ; Costa, Vital Paulino ; Cruz, Dianne A ; DuBiner, Harvey ; Ervin, John F ; Feldman, Robert M ; Flamme-Wiese, Miles ; Gaasterland, Douglas E ; Garnai, Sarah J ; Girkin, Christopher A ; Guirou, Nouhoum ; Guo, Xiuqing ; Haines, Jonathan L ; Hammond, Christopher J ; Herndon, Leon ; Hoffmann, Thomas J ; Hulette, Christine M ; Hydara, Abba ; Igo, Robert P ; Jorgenson, Eric ; Kabwe, Joyce ; Kilangalanga, Ngoy Janvier ; Kizor-Akaraiwe, Nkiru ; Kuchtey, Rachel W ; Lamari, Hasnaa ; Li, Zheng ; Liebmann, Jeffrey M ; Liu, Yutao ; Loos, Ruth J.F ; Melo, Monica B ; Moroi, Sayoko E ; Msosa, Joseph M ; Mullins, Robert F ; Nadkarni, Girish ; Napo, Abdoulaye ; Ng, Maggie C. Y ; Nunes, Hugo Freire ; Obeng-Nyarkoh, Ebenezer ; Okeke, Anthony ; Okeke, Suhanya ; Olaniyi, Olusegun ; Olawoye, Olusola ; Oliveira, Mariana Borges ; Pasquale, Louise R ; Perez-Grossmann, Rodolfo A ; Pericak-Vance, Margaret A ; Qin, Xue ; Ramsay, Michele ; Resnikoff, Serge ; Richards, Julia E ; Schimiti, Rui Barroso ; Sim, Kar Seng ; Sponsel, William E ; Svidnicki, Paulo Vinicius ; Thiadens, Alberta A. H. J ; Uche, Nkechinyere J ; van Duijn, Cornelia M ; de Vasconcellos, José Paulo Cabral ; Wiggs, Janey L ; Zangwill, Linda M ; Risch, Neil ; Milea, Dan ; Ashaye, Adeyinka ; Klaver, Caroline C. W ; Weinreb, Robert N ; Ashley Koch, Allison E ; Fingert, John H ; Khor, Chiea Chuen</creator><creatorcontrib>Hauser, Michael A ; Allingham, R. Rand ; Aung, Tin ; Van Der Heide, Carly J ; Taylor, Kent D ; Rotter, Jerome I ; Wang, Shih-Hsiu J ; Bonnemaijer, Pieter W. M ; Williams, Susan E ; Abdullahi, Sadiq M ; Abu-Amero, Khaled K ; Anderson, Michael G ; Akafo, Stephen ; Alhassan, Mahmoud B ; Asimadu, Ifeoma ; Ayyagari, Radha ; Bakayoko, Saydou ; Nyamsi, Prisca Biangoup ; Bowden, Donald W ; Bromley, William C ; Budenz, Donald L ; Carmichael, Trevor R ; Challa, Pratap ; Chen, Yii-Der Ida ; Chuka-Okosa, Chimdi M ; Cooke Bailey, Jessica N ; Costa, Vital Paulino ; Cruz, Dianne A ; DuBiner, Harvey ; Ervin, John F ; Feldman, Robert M ; Flamme-Wiese, Miles ; Gaasterland, Douglas E ; Garnai, Sarah J ; Girkin, Christopher A ; Guirou, Nouhoum ; Guo, Xiuqing ; Haines, Jonathan L ; Hammond, Christopher J ; Herndon, Leon ; Hoffmann, Thomas J ; Hulette, Christine M ; Hydara, Abba ; Igo, Robert P ; Jorgenson, Eric ; Kabwe, Joyce ; Kilangalanga, Ngoy Janvier ; Kizor-Akaraiwe, Nkiru ; Kuchtey, Rachel W ; Lamari, Hasnaa ; Li, Zheng ; Liebmann, Jeffrey M ; Liu, Yutao ; Loos, Ruth J.F ; Melo, Monica B ; Moroi, Sayoko E ; Msosa, Joseph M ; Mullins, Robert F ; Nadkarni, Girish ; Napo, Abdoulaye ; Ng, Maggie C. Y ; Nunes, Hugo Freire ; Obeng-Nyarkoh, Ebenezer ; Okeke, Anthony ; Okeke, Suhanya ; Olaniyi, Olusegun ; Olawoye, Olusola ; Oliveira, Mariana Borges ; Pasquale, Louise R ; Perez-Grossmann, Rodolfo A ; Pericak-Vance, Margaret A ; Qin, Xue ; Ramsay, Michele ; Resnikoff, Serge ; Richards, Julia E ; Schimiti, Rui Barroso ; Sim, Kar Seng ; Sponsel, William E ; Svidnicki, Paulo Vinicius ; Thiadens, Alberta A. H. J ; Uche, Nkechinyere J ; van Duijn, Cornelia M ; de Vasconcellos, José Paulo Cabral ; Wiggs, Janey L ; Zangwill, Linda M ; Risch, Neil ; Milea, Dan ; Ashaye, Adeyinka ; Klaver, Caroline C. W ; Weinreb, Robert N ; Ashley Koch, Allison E ; Fingert, John H ; Khor, Chiea Chuen ; Genetics of Glaucoma in People of African Descent (GGLAD) Consortium ; The Genetics of Glaucoma in People of African Descent (GGLAD) Consortium</creatorcontrib><description>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 < 5 × 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>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. 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.</description><identifier>ISSN: 0098-7484</identifier><identifier>ISSN: 1538-3598</identifier><identifier>EISSN: 1538-3598</identifier><identifier>DOI: 10.1001/jama.2019.16161</identifier><identifier>PMID: 31688885</identifier><language>eng</language><publisher>United States: American Medical Association</publisher><subject>Adaptor Proteins, Signal Transducing - genetics ; Aged ; Alleles ; Amyloid beta-Peptides - genetics ; Amyloid precursor protein ; Black People - genetics ; Case-Control Studies ; Chromosome 4 ; Chromosomes ; Female ; Gene frequency ; Genetic diversity ; Genetic Predisposition to Disease ; Genetic variance ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Genotype ; Glaucoma ; Glaucoma, Open-Angle - ethnology ; Glaucoma, Open-Angle - genetics ; Humans ; Immunohistochemistry ; Intraocular pressure ; Loci ; Male ; Meta-Analysis as Topic ; Middle Aged ; Optic neuropathy ; Original Investigation ; Pathogenesis ; Polymorphism, Single Nucleotide ; Population genetics ; Populations ; Pressure ; Risk assessment ; Risk Factors ; Systematic review ; Visual field ; Visual fields</subject><ispartof>JAMA : the journal of the American Medical Association, 2019-11, Vol.322 (17), p.1682-1691</ispartof><rights>Copyright American Medical Association Nov 5, 2019</rights><rights>Copyright 2019 American Medical Association. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a440t-f04b81fdb7897f15d026f56c56898afd4e00492af625c558b47c4cae6ab28a403</citedby><cites>FETCH-LOGICAL-a440t-f04b81fdb7897f15d026f56c56898afd4e00492af625c558b47c4cae6ab28a403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jamanetwork.com/journals/jama/articlepdf/10.1001/jama.2019.16161$$EPDF$$P50$$Gama$$H</linktopdf><linktohtml>$$Uhttps://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2019.16161$$EHTML$$P50$$Gama$$H</linktohtml><link.rule.ids>64,230,314,776,780,881,3327,27901,27902,76231,76234</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31688885$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hauser, Michael A</creatorcontrib><creatorcontrib>Allingham, R. Rand</creatorcontrib><creatorcontrib>Aung, Tin</creatorcontrib><creatorcontrib>Van Der Heide, Carly J</creatorcontrib><creatorcontrib>Taylor, Kent D</creatorcontrib><creatorcontrib>Rotter, Jerome I</creatorcontrib><creatorcontrib>Wang, Shih-Hsiu J</creatorcontrib><creatorcontrib>Bonnemaijer, Pieter W. M</creatorcontrib><creatorcontrib>Williams, Susan E</creatorcontrib><creatorcontrib>Abdullahi, Sadiq M</creatorcontrib><creatorcontrib>Abu-Amero, Khaled K</creatorcontrib><creatorcontrib>Anderson, Michael G</creatorcontrib><creatorcontrib>Akafo, Stephen</creatorcontrib><creatorcontrib>Alhassan, Mahmoud B</creatorcontrib><creatorcontrib>Asimadu, Ifeoma</creatorcontrib><creatorcontrib>Ayyagari, Radha</creatorcontrib><creatorcontrib>Bakayoko, Saydou</creatorcontrib><creatorcontrib>Nyamsi, Prisca Biangoup</creatorcontrib><creatorcontrib>Bowden, Donald W</creatorcontrib><creatorcontrib>Bromley, William C</creatorcontrib><creatorcontrib>Budenz, Donald L</creatorcontrib><creatorcontrib>Carmichael, Trevor R</creatorcontrib><creatorcontrib>Challa, Pratap</creatorcontrib><creatorcontrib>Chen, Yii-Der Ida</creatorcontrib><creatorcontrib>Chuka-Okosa, Chimdi M</creatorcontrib><creatorcontrib>Cooke Bailey, Jessica N</creatorcontrib><creatorcontrib>Costa, Vital Paulino</creatorcontrib><creatorcontrib>Cruz, Dianne A</creatorcontrib><creatorcontrib>DuBiner, Harvey</creatorcontrib><creatorcontrib>Ervin, John F</creatorcontrib><creatorcontrib>Feldman, Robert M</creatorcontrib><creatorcontrib>Flamme-Wiese, Miles</creatorcontrib><creatorcontrib>Gaasterland, Douglas E</creatorcontrib><creatorcontrib>Garnai, Sarah J</creatorcontrib><creatorcontrib>Girkin, Christopher A</creatorcontrib><creatorcontrib>Guirou, Nouhoum</creatorcontrib><creatorcontrib>Guo, Xiuqing</creatorcontrib><creatorcontrib>Haines, Jonathan L</creatorcontrib><creatorcontrib>Hammond, Christopher J</creatorcontrib><creatorcontrib>Herndon, Leon</creatorcontrib><creatorcontrib>Hoffmann, Thomas J</creatorcontrib><creatorcontrib>Hulette, Christine M</creatorcontrib><creatorcontrib>Hydara, Abba</creatorcontrib><creatorcontrib>Igo, Robert P</creatorcontrib><creatorcontrib>Jorgenson, Eric</creatorcontrib><creatorcontrib>Kabwe, Joyce</creatorcontrib><creatorcontrib>Kilangalanga, Ngoy Janvier</creatorcontrib><creatorcontrib>Kizor-Akaraiwe, Nkiru</creatorcontrib><creatorcontrib>Kuchtey, Rachel W</creatorcontrib><creatorcontrib>Lamari, Hasnaa</creatorcontrib><creatorcontrib>Li, Zheng</creatorcontrib><creatorcontrib>Liebmann, Jeffrey M</creatorcontrib><creatorcontrib>Liu, Yutao</creatorcontrib><creatorcontrib>Loos, Ruth J.F</creatorcontrib><creatorcontrib>Melo, Monica B</creatorcontrib><creatorcontrib>Moroi, Sayoko E</creatorcontrib><creatorcontrib>Msosa, Joseph M</creatorcontrib><creatorcontrib>Mullins, Robert F</creatorcontrib><creatorcontrib>Nadkarni, Girish</creatorcontrib><creatorcontrib>Napo, Abdoulaye</creatorcontrib><creatorcontrib>Ng, Maggie C. Y</creatorcontrib><creatorcontrib>Nunes, Hugo Freire</creatorcontrib><creatorcontrib>Obeng-Nyarkoh, Ebenezer</creatorcontrib><creatorcontrib>Okeke, Anthony</creatorcontrib><creatorcontrib>Okeke, Suhanya</creatorcontrib><creatorcontrib>Olaniyi, Olusegun</creatorcontrib><creatorcontrib>Olawoye, Olusola</creatorcontrib><creatorcontrib>Oliveira, Mariana Borges</creatorcontrib><creatorcontrib>Pasquale, Louise R</creatorcontrib><creatorcontrib>Perez-Grossmann, Rodolfo A</creatorcontrib><creatorcontrib>Pericak-Vance, Margaret A</creatorcontrib><creatorcontrib>Qin, Xue</creatorcontrib><creatorcontrib>Ramsay, Michele</creatorcontrib><creatorcontrib>Resnikoff, Serge</creatorcontrib><creatorcontrib>Richards, Julia E</creatorcontrib><creatorcontrib>Schimiti, Rui Barroso</creatorcontrib><creatorcontrib>Sim, Kar Seng</creatorcontrib><creatorcontrib>Sponsel, William E</creatorcontrib><creatorcontrib>Svidnicki, Paulo Vinicius</creatorcontrib><creatorcontrib>Thiadens, Alberta A. H. J</creatorcontrib><creatorcontrib>Uche, Nkechinyere J</creatorcontrib><creatorcontrib>van Duijn, Cornelia M</creatorcontrib><creatorcontrib>de Vasconcellos, José Paulo Cabral</creatorcontrib><creatorcontrib>Wiggs, Janey L</creatorcontrib><creatorcontrib>Zangwill, Linda M</creatorcontrib><creatorcontrib>Risch, Neil</creatorcontrib><creatorcontrib>Milea, Dan</creatorcontrib><creatorcontrib>Ashaye, Adeyinka</creatorcontrib><creatorcontrib>Klaver, Caroline C. W</creatorcontrib><creatorcontrib>Weinreb, Robert N</creatorcontrib><creatorcontrib>Ashley Koch, Allison E</creatorcontrib><creatorcontrib>Fingert, John H</creatorcontrib><creatorcontrib>Khor, Chiea Chuen</creatorcontrib><creatorcontrib>Genetics of Glaucoma in People of African Descent (GGLAD) Consortium</creatorcontrib><creatorcontrib>The Genetics of Glaucoma in People of African Descent (GGLAD) Consortium</creatorcontrib><title>Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry</title><title>JAMA : the journal of the American Medical Association</title><addtitle>JAMA</addtitle><description>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 < 5 × 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>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. 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.</description><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Aged</subject><subject>Alleles</subject><subject>Amyloid beta-Peptides - genetics</subject><subject>Amyloid precursor protein</subject><subject>Black People - genetics</subject><subject>Case-Control Studies</subject><subject>Chromosome 4</subject><subject>Chromosomes</subject><subject>Female</subject><subject>Gene frequency</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic variance</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genotype</subject><subject>Glaucoma</subject><subject>Glaucoma, Open-Angle - ethnology</subject><subject>Glaucoma, Open-Angle - genetics</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Intraocular pressure</subject><subject>Loci</subject><subject>Male</subject><subject>Meta-Analysis as Topic</subject><subject>Middle Aged</subject><subject>Optic neuropathy</subject><subject>Original Investigation</subject><subject>Pathogenesis</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population genetics</subject><subject>Populations</subject><subject>Pressure</subject><subject>Risk assessment</subject><subject>Risk Factors</subject><subject>Systematic review</subject><subject>Visual field</subject><subject>Visual fields</subject><issn>0098-7484</issn><issn>1538-3598</issn><issn>1538-3598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1r3DAQxU1paTZpz4UeiiCXXryRZEmWLwUT2m0gkB76cRRjWdrVYktbyQ7kv6-c3YS2o4MO7_eGebyieEfwmmBMrvYwwppi0qyJyO9FsSK8kmXFG_myWGHcyLJmkp0V5yntcR5S1a-Ls4oImYevil2bUtAOJhc8ChZtjDeT0-gnRAd-SuiXm3boW3QjxAd0dzC-bP12MGgzwKzDCKgdg9-iG9-7e9fPMJwsrY1Og0et1yZN8eFN8cpm0bw9_RfFjy-fv19_LW_vNjfX7W0JjOGptJh1kti-q2VTW8J7TIXlQnMhGwm2ZwZj1lCwgnLNuexYrZkGI6CjEhiuLopPx72HuRtNr42fIgzqcEygAjj1r-LdTm3DvRJScFrxvODjaUEMv-d8uxpd0mYYwJswJ0UrQqkQjNUZvfwP3Yc5-hxvoRinNWEsU1dHSseQUjT2-RiC1dKiWlpUS4vqscXs-PB3hmf-qbYMvD8Ci_FJpXWuvmmqP1EYogw</recordid><startdate>20191105</startdate><enddate>20191105</enddate><creator>Hauser, Michael A</creator><creator>Allingham, R. Rand</creator><creator>Aung, Tin</creator><creator>Van Der Heide, Carly J</creator><creator>Taylor, Kent D</creator><creator>Rotter, Jerome I</creator><creator>Wang, Shih-Hsiu J</creator><creator>Bonnemaijer, Pieter W. 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Y</creator><creator>Nunes, Hugo Freire</creator><creator>Obeng-Nyarkoh, Ebenezer</creator><creator>Okeke, Anthony</creator><creator>Okeke, Suhanya</creator><creator>Olaniyi, Olusegun</creator><creator>Olawoye, Olusola</creator><creator>Oliveira, Mariana Borges</creator><creator>Pasquale, Louise R</creator><creator>Perez-Grossmann, Rodolfo A</creator><creator>Pericak-Vance, Margaret A</creator><creator>Qin, Xue</creator><creator>Ramsay, Michele</creator><creator>Resnikoff, Serge</creator><creator>Richards, Julia E</creator><creator>Schimiti, Rui Barroso</creator><creator>Sim, Kar Seng</creator><creator>Sponsel, William E</creator><creator>Svidnicki, Paulo Vinicius</creator><creator>Thiadens, Alberta A. H. J</creator><creator>Uche, Nkechinyere J</creator><creator>van Duijn, Cornelia M</creator><creator>de Vasconcellos, José Paulo Cabral</creator><creator>Wiggs, Janey L</creator><creator>Zangwill, Linda M</creator><creator>Risch, Neil</creator><creator>Milea, Dan</creator><creator>Ashaye, Adeyinka</creator><creator>Klaver, Caroline C. W</creator><creator>Weinreb, Robert N</creator><creator>Ashley Koch, Allison E</creator><creator>Fingert, John H</creator><creator>Khor, Chiea Chuen</creator><general>American Medical Association</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7TK</scope><scope>7TS</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20191105</creationdate><title>Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry</title><author>Hauser, Michael A ; Allingham, R. Rand ; Aung, Tin ; Van Der Heide, Carly J ; Taylor, Kent D ; Rotter, Jerome I ; Wang, Shih-Hsiu J ; Bonnemaijer, Pieter W. M ; Williams, Susan E ; Abdullahi, Sadiq M ; Abu-Amero, Khaled K ; Anderson, Michael G ; Akafo, Stephen ; Alhassan, Mahmoud B ; Asimadu, Ifeoma ; Ayyagari, Radha ; Bakayoko, Saydou ; Nyamsi, Prisca Biangoup ; Bowden, Donald W ; Bromley, William C ; Budenz, Donald L ; Carmichael, Trevor R ; Challa, Pratap ; Chen, Yii-Der Ida ; Chuka-Okosa, Chimdi M ; Cooke Bailey, Jessica N ; Costa, Vital Paulino ; Cruz, Dianne A ; DuBiner, Harvey ; Ervin, John F ; Feldman, Robert M ; Flamme-Wiese, Miles ; Gaasterland, Douglas E ; Garnai, Sarah J ; Girkin, Christopher A ; Guirou, Nouhoum ; Guo, Xiuqing ; Haines, Jonathan L ; Hammond, Christopher J ; Herndon, Leon ; Hoffmann, Thomas J ; Hulette, Christine M ; Hydara, Abba ; Igo, Robert P ; Jorgenson, Eric ; Kabwe, Joyce ; Kilangalanga, Ngoy Janvier ; Kizor-Akaraiwe, Nkiru ; Kuchtey, Rachel W ; Lamari, Hasnaa ; Li, Zheng ; Liebmann, Jeffrey M ; Liu, Yutao ; Loos, Ruth J.F ; Melo, Monica B ; Moroi, Sayoko E ; Msosa, Joseph M ; Mullins, Robert F ; Nadkarni, Girish ; Napo, Abdoulaye ; Ng, Maggie C. Y ; Nunes, Hugo Freire ; Obeng-Nyarkoh, Ebenezer ; Okeke, Anthony ; Okeke, Suhanya ; Olaniyi, Olusegun ; Olawoye, Olusola ; Oliveira, Mariana Borges ; Pasquale, Louise R ; Perez-Grossmann, Rodolfo A ; Pericak-Vance, Margaret A ; Qin, Xue ; Ramsay, Michele ; Resnikoff, Serge ; Richards, Julia E ; Schimiti, Rui Barroso ; Sim, Kar Seng ; Sponsel, William E ; Svidnicki, Paulo Vinicius ; Thiadens, Alberta A. H. J ; Uche, Nkechinyere J ; van Duijn, Cornelia M ; de Vasconcellos, José Paulo Cabral ; Wiggs, Janey L ; Zangwill, Linda M ; Risch, Neil ; Milea, Dan ; Ashaye, Adeyinka ; Klaver, Caroline C. W ; Weinreb, Robert N ; Ashley Koch, Allison E ; Fingert, John H ; Khor, Chiea Chuen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a440t-f04b81fdb7897f15d026f56c56898afd4e00492af625c558b47c4cae6ab28a403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adaptor Proteins, Signal Transducing - genetics</topic><topic>Aged</topic><topic>Alleles</topic><topic>Amyloid beta-Peptides - genetics</topic><topic>Amyloid precursor protein</topic><topic>Black People - genetics</topic><topic>Case-Control Studies</topic><topic>Chromosome 4</topic><topic>Chromosomes</topic><topic>Female</topic><topic>Gene frequency</topic><topic>Genetic diversity</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic variance</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Genotype</topic><topic>Glaucoma</topic><topic>Glaucoma, Open-Angle - ethnology</topic><topic>Glaucoma, Open-Angle - genetics</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Intraocular pressure</topic><topic>Loci</topic><topic>Male</topic><topic>Meta-Analysis as Topic</topic><topic>Middle Aged</topic><topic>Optic neuropathy</topic><topic>Original Investigation</topic><topic>Pathogenesis</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population genetics</topic><topic>Populations</topic><topic>Pressure</topic><topic>Risk assessment</topic><topic>Risk Factors</topic><topic>Systematic review</topic><topic>Visual field</topic><topic>Visual fields</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hauser, Michael A</creatorcontrib><creatorcontrib>Allingham, R. 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Y</creatorcontrib><creatorcontrib>Nunes, Hugo Freire</creatorcontrib><creatorcontrib>Obeng-Nyarkoh, Ebenezer</creatorcontrib><creatorcontrib>Okeke, Anthony</creatorcontrib><creatorcontrib>Okeke, Suhanya</creatorcontrib><creatorcontrib>Olaniyi, Olusegun</creatorcontrib><creatorcontrib>Olawoye, Olusola</creatorcontrib><creatorcontrib>Oliveira, Mariana Borges</creatorcontrib><creatorcontrib>Pasquale, Louise R</creatorcontrib><creatorcontrib>Perez-Grossmann, Rodolfo A</creatorcontrib><creatorcontrib>Pericak-Vance, Margaret A</creatorcontrib><creatorcontrib>Qin, Xue</creatorcontrib><creatorcontrib>Ramsay, Michele</creatorcontrib><creatorcontrib>Resnikoff, Serge</creatorcontrib><creatorcontrib>Richards, Julia E</creatorcontrib><creatorcontrib>Schimiti, Rui Barroso</creatorcontrib><creatorcontrib>Sim, Kar Seng</creatorcontrib><creatorcontrib>Sponsel, William E</creatorcontrib><creatorcontrib>Svidnicki, Paulo Vinicius</creatorcontrib><creatorcontrib>Thiadens, Alberta A. H. J</creatorcontrib><creatorcontrib>Uche, Nkechinyere J</creatorcontrib><creatorcontrib>van Duijn, Cornelia M</creatorcontrib><creatorcontrib>de Vasconcellos, José Paulo Cabral</creatorcontrib><creatorcontrib>Wiggs, Janey L</creatorcontrib><creatorcontrib>Zangwill, Linda M</creatorcontrib><creatorcontrib>Risch, Neil</creatorcontrib><creatorcontrib>Milea, Dan</creatorcontrib><creatorcontrib>Ashaye, Adeyinka</creatorcontrib><creatorcontrib>Klaver, Caroline C. W</creatorcontrib><creatorcontrib>Weinreb, Robert N</creatorcontrib><creatorcontrib>Ashley Koch, Allison E</creatorcontrib><creatorcontrib>Fingert, John H</creatorcontrib><creatorcontrib>Khor, Chiea Chuen</creatorcontrib><creatorcontrib>Genetics of Glaucoma in People of African Descent (GGLAD) Consortium</creatorcontrib><creatorcontrib>The Genetics of Glaucoma in People of African Descent (GGLAD) Consortium</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>JAMA : the journal of the American Medical Association</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hauser, Michael A</au><au>Allingham, R. Rand</au><au>Aung, Tin</au><au>Van Der Heide, Carly J</au><au>Taylor, Kent D</au><au>Rotter, Jerome I</au><au>Wang, Shih-Hsiu J</au><au>Bonnemaijer, Pieter W. M</au><au>Williams, Susan E</au><au>Abdullahi, Sadiq M</au><au>Abu-Amero, Khaled K</au><au>Anderson, Michael G</au><au>Akafo, Stephen</au><au>Alhassan, Mahmoud B</au><au>Asimadu, Ifeoma</au><au>Ayyagari, Radha</au><au>Bakayoko, Saydou</au><au>Nyamsi, Prisca Biangoup</au><au>Bowden, Donald W</au><au>Bromley, William C</au><au>Budenz, Donald L</au><au>Carmichael, Trevor R</au><au>Challa, Pratap</au><au>Chen, Yii-Der Ida</au><au>Chuka-Okosa, Chimdi M</au><au>Cooke Bailey, Jessica N</au><au>Costa, Vital Paulino</au><au>Cruz, Dianne A</au><au>DuBiner, Harvey</au><au>Ervin, John F</au><au>Feldman, Robert M</au><au>Flamme-Wiese, Miles</au><au>Gaasterland, Douglas E</au><au>Garnai, Sarah J</au><au>Girkin, Christopher A</au><au>Guirou, Nouhoum</au><au>Guo, Xiuqing</au><au>Haines, Jonathan L</au><au>Hammond, Christopher J</au><au>Herndon, Leon</au><au>Hoffmann, Thomas J</au><au>Hulette, Christine M</au><au>Hydara, Abba</au><au>Igo, Robert P</au><au>Jorgenson, Eric</au><au>Kabwe, Joyce</au><au>Kilangalanga, Ngoy Janvier</au><au>Kizor-Akaraiwe, Nkiru</au><au>Kuchtey, Rachel W</au><au>Lamari, Hasnaa</au><au>Li, Zheng</au><au>Liebmann, Jeffrey M</au><au>Liu, Yutao</au><au>Loos, Ruth J.F</au><au>Melo, Monica B</au><au>Moroi, Sayoko E</au><au>Msosa, Joseph M</au><au>Mullins, Robert F</au><au>Nadkarni, Girish</au><au>Napo, Abdoulaye</au><au>Ng, Maggie C. Y</au><au>Nunes, Hugo Freire</au><au>Obeng-Nyarkoh, Ebenezer</au><au>Okeke, Anthony</au><au>Okeke, Suhanya</au><au>Olaniyi, Olusegun</au><au>Olawoye, Olusola</au><au>Oliveira, Mariana Borges</au><au>Pasquale, Louise R</au><au>Perez-Grossmann, Rodolfo A</au><au>Pericak-Vance, Margaret A</au><au>Qin, Xue</au><au>Ramsay, Michele</au><au>Resnikoff, Serge</au><au>Richards, Julia E</au><au>Schimiti, Rui Barroso</au><au>Sim, Kar Seng</au><au>Sponsel, William E</au><au>Svidnicki, Paulo Vinicius</au><au>Thiadens, Alberta A. H. J</au><au>Uche, Nkechinyere J</au><au>van Duijn, Cornelia M</au><au>de Vasconcellos, José Paulo Cabral</au><au>Wiggs, Janey L</au><au>Zangwill, Linda M</au><au>Risch, Neil</au><au>Milea, Dan</au><au>Ashaye, Adeyinka</au><au>Klaver, Caroline C. W</au><au>Weinreb, Robert N</au><au>Ashley Koch, Allison E</au><au>Fingert, John H</au><au>Khor, Chiea Chuen</au><aucorp>Genetics of Glaucoma in People of African Descent (GGLAD) Consortium</aucorp><aucorp>The Genetics of Glaucoma in People of African Descent (GGLAD) Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry</atitle><jtitle>JAMA : the journal of the American Medical Association</jtitle><addtitle>JAMA</addtitle><date>2019-11-05</date><risdate>2019</risdate><volume>322</volume><issue>17</issue><spage>1682</spage><epage>1691</epage><pages>1682-1691</pages><issn>0098-7484</issn><issn>1538-3598</issn><eissn>1538-3598</eissn><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 < 5 × 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>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. 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.</abstract><cop>United States</cop><pub>American Medical Association</pub><pmid>31688885</pmid><doi>10.1001/jama.2019.16161</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0098-7484 |
| ispartof | JAMA : the journal of the American Medical Association, 2019-11, Vol.322 (17), p.1682-1691 |
| issn | 0098-7484 1538-3598 1538-3598 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6865235 |
| source | MEDLINE; American Medical Association Journals |
| subjects | Adaptor Proteins, Signal Transducing - genetics Aged Alleles Amyloid beta-Peptides - genetics Amyloid precursor protein Black People - genetics Case-Control Studies Chromosome 4 Chromosomes Female Gene frequency Genetic diversity Genetic Predisposition to Disease Genetic variance Genome-wide association studies Genome-Wide Association Study Genomes Genotype Glaucoma Glaucoma, Open-Angle - ethnology Glaucoma, Open-Angle - genetics Humans Immunohistochemistry Intraocular pressure Loci Male Meta-Analysis as Topic Middle Aged Optic neuropathy Original Investigation Pathogenesis Polymorphism, Single Nucleotide Population genetics Populations Pressure Risk assessment Risk Factors Systematic review Visual field Visual fields |
| title | Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T20%3A47%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Association%20of%20Genetic%20Variants%20With%20Primary%20Open-Angle%20Glaucoma%20Among%20Individuals%20With%20African%20Ancestry&rft.jtitle=JAMA%20:%20the%20journal%20of%20the%20American%20Medical%20Association&rft.au=Hauser,%20Michael%20A&rft.aucorp=Genetics%20of%20Glaucoma%20in%20People%20of%20African%20Descent%20(GGLAD)%20Consortium&rft.date=2019-11-05&rft.volume=322&rft.issue=17&rft.spage=1682&rft.epage=1691&rft.pages=1682-1691&rft.issn=0098-7484&rft.eissn=1538-3598&rft_id=info:doi/10.1001/jama.2019.16161&rft_dat=%3Cproquest_pubme%3E2314527144%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2314527144&rft_id=info:pmid/31688885&rft_ama_id=2753899&rfr_iscdi=true |