Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations
Year: 2018
Type: article
Study design: Observational Study
Abstract: Primary open angle glaucoma (POAG) is a complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. We conducted a genome-wide association study in 1113 POAG cases and 1826 controls from Tanzanian, South African and African American study samples. Apart from confirming evidence of association at TXNRD2 (rs16984299; OR [T] 1.20; P = 0.003), we found that a genetic risk score combining the effects of the 15 previously reported POAG loci was significantly associated with POAG in our samples (OR 1.56; 95% CI 1.26–1.93; P = 4.79 × 10 −5 ). By genome-wide association testing we identified a novel candidate locus, rs141186647, harboring EXOC4 (OR [A] 0.48; P = 3.75 × 10 −8 ), a gene transcribing a component of the exocyst complex involved in vesicle transport. The low frequency and high degree of genetic heterogeneity at this region hampered validation of this finding in predominantly West-African replication sets. Our results suggest that established genetic risk factors play a role in African POAG, however, they do not explain the higher disease load. The high heterogeneity within Africans remains a challenge to identify the genetic commonalities for POAG in this ethnicity, and demands studies of extremely large size.
Source: Human Genetics
Authors: GIGA Study Group, Pieter W. M. Bonnemaijer, Adriana I. Iglesias, Girish N. Nadkarni, Anna J. Sanyiwa, Hassan G. Hassan, Colin Cook, Mark Simcoe, Kent D. Taylor, Claudia Schurmann, Gillian M. Belbin, Eimear E. Kenny, Erwin P. Bottinger, Suzanne van de Laar, Susan E. I. Wiliams, Stephen K. Akafo, Adeyinka O. Ashaye, Linda M. Zangwill, Christopher A. Girkin, Maggie C. Y. Ng, Jerome I. Rotter, Robert N. Weinreb, Zheng Li, R. Rand Allingham, Abhishek Nag, Pirro G. Hysi, Magda A. Meester-Smoor, Janey L. Wiggs, Michael A. Hauser, Christopher J. Hammond, Hans G. Lemij, Ruth J. F. Loos, Cornelia M. van Duijn, Alberta A. H. J. Thiadens, Caroline C. W. Klaver
Institutions: Erasmus MC, Rotterdam Eye Hospital, Icahn School of Medicine at Mount Sinai, Muhimbili University of Health and Allied Sciences, Muhimbili National Hospital, University of Cape Town, King's College London, The Lundquist Institute, Harbor–UCLA Medical Center, University Medical Center Utrecht, University of the Witwatersrand, University of Ghana, University of Ibadan, University of California San Diego, University of Alabama at Birmingham, UAB Medicine, Wake Forest University Health Sciences, Wake Forest University, Genome Institute of Singapore, Duke University, Harvard University, Duke Medical Center, Radboud University Medical Center
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,690
Funders: Andrea and Charles Bronfman Philanthropies, BrightFocus Foundation, University of Michigan, International Glaucoma Association, National Institute for Health and Care Research, Stichting Combined Ophthalmic Research Rotterdam, Algemene Nederlandse Vereniging ter voorkoming van Blindheid, Landelijke Stichting voor Blinden en Slechtzienden, Stichting Glaucoomfonds, Rotterdamse Stichting Blindenbelangen, National Institutes of Health, College of Pharmacy, University of Michigan, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Eye Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: G1462415530, G151483383, Long Noncoding RNA lncLOXL1 and Exfoliation Syndrome., G2495855894, Genetics of African American Type 2 Diabetes, Transforming Genomics with 5 PB Big Omics Data Engine Cray CS300-AC Supercomputer, G3707580291, G3746371656, Integrative Study of Genomics, Transcriptiomics, and Metabolomics in Type 2 Diabetes, Mapping Genes for NIDDM Nephropathy in African Americans, xADAGES III: Contribution of genotype to glaucoma phenotype in African Americans, Diverse ancestry biobank to map biomedical traits and elucidate health disparitie, African Descent and Glaucoma Evaluation (ADAGES) II: Glaucoma Progression, G5198616249, G5277791807, G5352529209, Diagnostic Innovations in Glaucoma Study (DIGS): Functional Impairment, An Integrative Genomic Approach to APOL1-Associated Nephropathy., Search for obesity-associated genes with protective effects on metabolic health, Molecular Genetics of Norma Tension Glaucoma, Genetics In Glaucoma patients of African descent, The GIGA Study, G596646106, Study of coding variants in human obesity and their functional characterization using human iPSC-derived cellular models, Leveraging ancestral diversity to map adiposity loci in Hispanics, Data commons for 'omic, microscopy and analysis core facilities, GENETIC ANALYSIS OF HUMAN HYPERTENSIVE ESRD, Genetic Determinants of Adiposity in African Americans, G6617052721, G7065342431, G7804247782, G8571936473, G9000140433, G9000196665, G9000337785, P30 Core Grant for Vision Research, NEIGHBORHOOD Consortium for POAG Genetics, Diabetes Research Center (DRC), NEI Center Core Grant for Vision Research, UCLA Clinical and Translational Science Institute, G939061647
OpenAlex ID: W2897631476