title: Common variants on chromosome 2 and risk of primary open-angle glaucoma in the Afro-Caribbean population of Barbados.
abstract: Primary open-angle glaucoma (POAG) is the second leading cause of blindness worldwide. Although a number of genetic loci have shown association or genetic linkage to monogenic forms of POAG, the identified genes and loci do not appear to have a major role in the common POAG phenotype. We seek to identify genetic loci that appear to be major risk factors for POAG in the Afro-Caribbean population of Barbados, West Indies. We performed linkage analyses in 146 multiplex families ascertained through the Barbados Family Study of Glaucoma (BFSG) and identified a strong linkage signal on chromosome 2p (logarithm of odds score = 6.64 at = 0 with marker D2S2156). We subsequently performed case-control analyses using unrelated affected individuals and unaffected controls. A set of SNPs on chromosome 2p was evaluated in two independent groups of BFSG participants, a discovery group (130 POAG cases, 65 controls) and a replication group (122 POAG cases, 65 controls), and a strong association was identified with POAG and rs12994401 in both groups (P < 3.34 E-09 and P < 1.21E-12, respectively). The associated SNPs form a common disease haplotype. In summary, we have identified a locus with a major impact on susceptibility to the common POAG phenotype in an Afro-Caribbean population in Barbados. Our approach illustrates the merit of using an isolated population enriched with common disease variants as an efficient method to identify genetic underpinning of POAG.
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, and Barbados Family Study Group, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jiao
authors.forename: Zhenglin
authors.initials: Z
authors.lastname: Yang
authors.forename: Xian
authors.initials: X
authors.lastname: Yang
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Chen
authors.forename: Zongzhong
authors.initials: Z
authors.lastname: Tong
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.forename: Jiexi
authors.initials: J
authors.lastname: Zeng
authors.forename: Haoyu
authors.initials: H
authors.lastname: Chen
authors.forename: Daniel
authors.initials: D
authors.lastname: Gibbs
authors.forename: Xufang
authors.initials: X
authors.lastname: Sun
authors.forename: Bei
authors.initials: B
authors.lastname: Li
authors.forename: W Scott
authors.initials: WS
authors.lastname: Wakins
authors.forename: Cynthia
authors.initials: C
authors.lastname: Meyer
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Wang
authors.forename: Daniel
authors.initials: D
authors.lastname: Kasuga
authors.forename: Matthew
authors.initials: M
authors.lastname: Bedell
authors.forename: Erik
authors.initials: E
authors.lastname: Pearson
authors.forename: Robert N
authors.initials: RN
authors.lastname: Weinreb
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Leske
authors.forename: Anselm
authors.initials: A
authors.lastname: Hennis
authors.forename: Andrew
authors.initials: A
authors.lastname: DeWan
authors.forename: Barbara
authors.initials: B
authors.lastname: Nemesure
authors.forename: Lynn B
authors.initials: LB
authors.lastname: Jorde
authors.forename: Josephine
authors.initials: J
authors.lastname: Hoh
authors.forename: J Fielding
authors.initials: JF
authors.lastname: Hejtmancik
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
mesh_terms: D001460:Barbados; D044383:Black People / Q000208:ethnology / Q000235:genetics; D016022:Case-Control Studies; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000208:ethnology / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors