Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations.
Клиническое исследованиеСтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Bonnemaijer Pieter W M, Iglesias Adriana I, Nadkarni Girish N, Sanyiwa Anna J, Hassan Hassan G, Cook Colin, GIGA Study Group, Simcoe Mark, Taylor Kent D, Schurmann Claudia, Belbin Gillian M, Kenny Eimear E, Bottinger Erwin P, van de Laar Suzanne, Wiliams Susan E I, Akafo Stephen K, Ashaye Adeyinka O, Zangwill Linda M, Girkin Christopher A, Ng Maggie C Y, Rotter Jerome I, Weinreb Robert N, Li Zheng, Allingham R Rand, Eyes of Africa Genetics Consortium, Nag Abhishek, Hysi Pirro G, Meester-Smoor Magda A, Wiggs Janey L, NEIGHBORHOOD Consortium, Hauser Michael A, Hammond Christopher J, Lemij Hans G, Loos Ruth J F, van Duijn Cornelia M, Thiadens Alberta A H J, Klaver Caroline C W
Аннотация
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.