Common variants on chromosome 2 and risk of primary open-angle glaucoma in the Afro-Caribbean population of Barbados.
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.
Jiao
Xiaodong
X
Ophthalmic Genetics and Visual Function Branch, National Eye Institute, and Barbados Family Study Group, National Institutes of Health, Bethesda, MD 20892, USA.
Yang
Zhenglin
Z
Yang
Xian
X
Chen
Yuhong
Y
Tong
Zongzhong
Z
Zhao
Chao
C
Zeng
Jiexi
J
Chen
Haoyu
H
Gibbs
Daniel
D
Sun
Xufang
X
Li
Bei
B
Wakins
W Scott
WS
Meyer
Cynthia
C
Wang
Xiaolei
X
Kasuga
Daniel
D
Bedell
Matthew
M
Pearson
Erik
E
Weinreb
Robert N
RN
Leske
M Cristina
MC
Hennis
Anselm
A
DeWan
Andrew
A
Nemesure
Barbara
B
Jorde
Lynn B
LB
Hoh
Josephine
J
Hejtmancik
J Fielding
JF
Zhang
Kang
K
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