Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations

, 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 NgJerome 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

Research output: Contribution to journalArticleResearchpeer-review


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.

Original languageEnglish
Pages (from-to)847-862
Number of pages16
JournalHuman Genetics
Issue number10
Publication statusPublished - Oct 2018


  • African Continental Ancestry Group/genetics
  • Aged
  • Aged, 80 and over
  • Female
  • Genetic Loci
  • Genome-Wide Association Study
  • Glaucoma, Open-Angle/genetics
  • Humans
  • Male
  • Middle Aged
  • Thioredoxin Reductase 2/genetics
  • Vesicular Transport Proteins/genetics


Dive into the research topics of 'Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations'. Together they form a unique fingerprint.

Cite this