Abstract:
Endophenotypes are measurable or quantifiable clinical traits (QTs) which are highly newlineinherited. Identification of gene loci for these precursor risk traits has potential significance newlinein risk prediction and disease management. Ocular QTs like optic disc area (ODA), vertical newlinecup disc ratio (VCDR) etc., are implicated in eye diseases like glaucoma, myopia and newlineothers in different populations. The current study was undertaken to evaluate the newlineassociation of known QT loci with endophenotypes like AL, CCT, IOP and VCDR. newlineMethodology newlineWe included three different sample sets namely (a) multigenerational consanguineous newlinefamilies without any history of ocular disorders (b) POAG and (c) myopia. The samples newlinewere recruited from the Chennai glaucoma study, INDO-US study on QTs and Myopia newlinestudy after detailed clinical evaluation. Heparinised blood sample was collected from these newlinepatients after informed consent for DNA extraction and subsequent genotype analysis. newlineThe association of SNPs flanking ATOH7 (rs1900004, rs3858145, rs17231602, rs4746741) newlineand ZNF469 (rs77330683) with optic disc parameters was analysed in large newlineconsanguineous south Indian pedigrees. The individuals were genotyped by direct newlinesequencing. The effect size (and#946;) and P value were obtained using the QFAM procedure in newlinePLINK, which performs a simple linear regression of phenotype on genotype, and then newlineuses a special permutation procedure to correct for family structure. newlineThe distribution of SNPs rs1900004, rs3858145 (ATOH7), rs10483727 (SIX1/SIX6), newliners1063192 (CDKN2B), rs9607469 (CARD10), rs1192415 (CDC7) in POAG (cases= 97) newlineand controls= 360) and LOXL1 (rs3825942 and rs1048661) in Pseudoexfoliation newline(cases=114 and controls=135) were analysed for putative association with IOP, AL, CCT newlineand VCDR. A model-based (additive, recessive, dominant) Chi square and linear newlineregression analysis was performed to analyse the statistical significance; while the newlineinteraction analysis was performed by logistic regression methods. newlineMutation screening of the eye development genes involved in AL .
