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Genomewide Scan and Fine Mapping of Quantitative Trait Loci for Intraocular Pressure on 5q and 14q in West Africans

¹From the National Human Genome Center and the ²Department of Ophthalmology, Howard University, College of Medicine, Washington, DC; the ³Department of Medicine, University of Science and Technology, Kumasi, Ghana; the ⁴College of Medicine, Endocrine and Metabolic Unit, University of Lagos, Lagos, Nigeria; the ⁵Department of Medicine and Ophthalmology, University of Nigeria Teaching Hospital, Enugu, Nigeria; and the ⁶Department of Medicine and Surgery, University of Ghana Medical School, Accra, Ghana.

PURPOSE. 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.

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