Genomewide scan and fine mapping of quantitative trait loci for intraocular pressure on 5q and 14q in West Africans.
OBJECTIVE
High intraocular pressure (IOP) is a major risk factor for glaucoma, one of the leading causes of blindness worldwide. Because it has been demonstrated that African populations are at increased risk for glaucoma, the authors investigated the genetic basis of IOP in a sample of West Africans with type 2 diabetes (T2D) from Ghana and Nigeria.


METHODS
Genomewide linkage analysis was conducted for loci linked to IOP (measured by applanation tonometry) in 244 affected sibling pairs with T2D using 372 autosomal short-tandem repeat markers at an average spacing of 9 cM.


RESULTS
Multipoint variance components linkage analyses revealed suggestive linkage on chromosome 5 (5q22) with a logarithm of odds (LOD) score of 2.50 (nominal P = 0.0003; empiric P = 0.0004) and on chromosome 14 (14q22) with an LOD score of 2.95 (nominal P = 0.0001; empiric P = 0.0003). Fine mapping at a marker density of 2 cM in the 5q region confirmed the linkage signal, with an increase in peak LOD score to 4.91.


CONCLUSIONS
The strong signal on chromosome 5 lies in the region in which a novel gene, WDR36, in the GLC1G locus was recently identified as causative for adult-onset primary open-angle glaucoma and provides additional evidence that chromosome 5 contains susceptibility loci for glaucoma in multiple human populations. The evidence provided in this study is particularly important given the evolutionary history of these West African populations and the recent ancestral relationship to African Americans-a population with one of the highest rates of diabetes and associated complications (including glaucoma) in the world.
Rotimi
Charles N
CN
National Human Genome Center, Howard University, College of Medicine, Washington, DC 20059, USA. crotimi@howard.edu
Chen
Guanjie
G
Adeyemo
Adebowale A
AA
Jones
Leslie S
LS
Agyenim-Boateng
Kofi
K
Eghan
Benjamin A
BA
Zhou
Jie
J
Doumatey
Ayo
A
Lashley
Karrie
K
Huang
Hanxia
H
Fasanmade
Olufemi
O
Akinsola
Folasade B
FB
Ezepue
Felix
F
Amoah
Albert
A
Akafo
Stephen
S
Chen
Yuanxiu
Y
Oli
Johnnie
J
Johnson
Thomas
T
D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005869:Ghana / Q000453:epidemiology; D005902:Glaucoma, Open-Angle / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009549:Nigeria / Q000453:epidemiology; D016017:Odds Ratio; D040641:Quantitative Trait Loci
D005819:Genetic Markers