Replication of a glaucoma candidate gene on 5q22.1 for intraocular pressure in mongolian populations: the GENDISCAN Project.
OBJECTIVE
Glaucoma is the second most frequent cause of visual impairment worldwide. Elevated intraocular pressure (IOP) causes glaucomatous optic nerve damage, especially in the primary open-angle glaucoma (POAG) subtype. As most previous studies on IOP genetics were analyses of glaucomatous families, a study of general pedigrees will provide additional information on genetic etiology.


METHODS
This work was part of the GENDISCAN study (Gene Discovery for Complex Traits in Isolated Large Families of Asians of the Northeast), which recruited families from population isolates in Mongolia. IOP (obtained by a noncontact method), epidemiologic, and clinical information were collected from 1451 healthy individuals of 142 families. From these individuals, 390 genome-wide short tandem repeat markers were genotyped. Variance component-based linkage analysis was applied to pursue candidate loci explaining IOP variation.


RESULTS
The mean IOP was 13.6 mm Hg in the men and 13.7 mm Hg in the women, inversely associated with aging (beta = -0.05; P <or= 0.0001). The heritability of IOP was 0.48. Suggestive linkage evidence was found on the 5q22.1 region (LOD score, 2.4), which harbors WDR36, a candidate gene for POAG. In addition, possible linkage evidence was found on 2q37.1, 7p15.3, 17q25.3, and 20p13.


CONCLUSIONS
The findings support evidence that IOP regulation is associated with the 5q22.1 region, along with four other candidate regions. The present results further indicate that genetic factors regulating IOP in the general Mongolian population are linked to regions harboring POAG genes, suggesting that common genetic factors influence both normal IOP variation and POAG occurrence. In addition, the replication of previous findings concerning POAG regions from the white and African populations implies that the mutations regulating IOP levels did not occur recently.
Lee
Mi Kyeong
MK
Complex Disease Genetic Epidemiology Branch, Department of Epidemiology, Graduate School of Public Health and Institute of Environment and Health, and.
Woo
Se Joon
SJ
Kim
Jong-Il
JI
Cho
Sung-Il
SI
Kim
Ho
H
Sung
Joohon
J
Seo
Jeong-Sun
JS
Kim
Dong Myung
DM
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D008986:Mongolia / Q000453:epidemiology; D010375:Pedigree; D055815:Young Adult
D005819:Genetic Markers