Represents association data of AFAP1 SNP in discovery and validation phase. (XLSX 9Â kb

Abhijit Sen (47513)

Analabha Basu (441412)

Anchal Sharma (3465371)

Arijit Mukhopadhyay (441411)

Giovanna Alfano (1805761)

Iman Bhattacharya (3465368)

Jharna Ray (3465377)

Jyoti Agrawal (3465362)

Kiran Narta (3465380)

Kunal Ray (47515)

Lalit Kaurani (3465365)

Mansi Vishal (441410)

Naushin Waseem (531895)

Shomi Bhattacharya (3465374)

Suddhasil Mookherjee (47510)

Susanta Roychoudhury (159129)

BMC Medical Genomics

PubMed

Contains figure representing quality control of the validation data. (A) Genotype concordance of technical replicates. X-axis represents the replicate sample Id and Y-axis shows percentage genotype concordance. (B) Cluster of rs10763643 in validation cohort. The gentrain score is 0.70. (TIF 158Â kb

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Additional file 5: of Genetic association and stress mediated down-regulation in trabecular meshwork implicates MPP7 as a novel candidate gene in primary open angle glaucoma

Contains table representing association of published SNPs form reported loci. (XLSX 11Â kb

Additional file 9: of Genetic association and stress mediated down-regulation in trabecular meshwork implicates MPP7 as a novel candidate gene in primary open angle glaucoma

Contains figure representing genotype and allele error rate of individual and combined dataset of CEU and GIH populations of HAPMAP phase3. Error rates of chromosome 6 and chromosome 21 are shown as example here. The similar distribution of error rates was observed for every autosome. (TIF 646Â kb

Additional file 3: of Genetic association and stress mediated down-regulation in trabecular meshwork implicates MPP7 as a novel candidate gene in primary open angle glaucoma

Mansi Vishal

Anchal Sharma

Lalit Kaurani

Giovanna Alfano

Suddhasil Mookherjee

Kiran Narta

Jyoti Agrawal

Iman Bhattacharya

Susanta Roychoudhury

Jharna Ray

Naushin H. Waseem

Shomi S. Bhattacharya

Analabha Basu

Abhijit Sen

Kunal Ray

Arijit Mukhopadhyay

Crossref

Genetic association and stress mediated down-regulation in trabecular meshwork implicates MPP7 as a novel candidate gene in primary open angle glaucoma

Background: Glaucoma is the largest cause of irreversible blindness affecting more than 60 million people globally.The disease is defined as a gradual loss of peripheral vision due to death of Retinal Ganglion Cells (RGC). The RGC death is largely influenced by the rate of aqueous humor production by ciliary processes and its passage through the trabecular meshwork (TM) in the anterior part of the eye. Primary open angle glaucoma (POAG), the most common subtype, is a genetically complex disease. Multiple genes and many loci have been reported to be involved in POAG but taken together they explain less than 10 % of the patients from a genetic perspective warranting more studies in different world populations. The purpose of this study was to perform genome-wide search for common variants associated with POAG in an east-Indian population. Methods: The study recruited 746 POAG cases and 697 controls distributed into discovery and validation cohorts. Inthe discovery phase, genome-wide genotype data was generated on Illumina Infinium 660 W-Quad platform and thesignificant SNPs were genotyped using Illumina GGGT assay in the second phase. Logistic regression was used to testassociation in the discovery phase to adjust for population sub-structure and chi-square test was used for associationanalysis in validation phase. Publicly available expression dataset for trabecular meshwork was used to check forexpression of the candidate gene under cyclic mechanical stress. Western blot and immunofluorescence experimentswere performed in human TM cells and murine eye, respectively to check for expression of the candidate gene. Results: Meta-analysis of discovery and validation phase data revealed the association of rs7916852 in MPP7 gene(p = 5.7x10−7) with POAG. We have shown abundant expression of MPP7 in the HTM cells. Expression analysis showsthat upon cyclic mechanical stress MPP7 was significantly down-regulated in HTM (Fold change: 2.6; p = 0.018). MPP7protein expression was also found to be enriched in the ciliary processes of the murine eye. Conclusion: Using a genome-wide approach we have identified MPP7 as a novel candidate gene for POAG withevidence of its expression in relevant ocular tissues and dysregulation under mechanical stress possibly mimicking thedisease scenario

Vishal, M

Sharma, A

Kaurani, L

Alfano, G

Mookerjee, S

Narta, K

Agrawal, J

Bhattacharya, I

Roychoudhury, S

Ray, J

Waseem, NH

Bhattacharya, SS

Basu, A

Sen, A

Ray, K

Mukhopadhyay, A

University of Salford Institutional Repository

Additional file 11: of Genetic association and stress mediated down-regulation in trabecular meshwork implicates MPP7 as a novel candidate gene in primary open angle glaucoma

Contains a table representing the association of 494 validation phase SNPs in discovery, validation phase and meta-analysis of both. (XLSX 59Â kb

Additional file 2: of Genetic association and stress mediated down-regulation in trabecular meshwork implicates MPP7 as a novel candidate gene in primary open angle glaucoma

Contains table representing SNPs removed from the analysis for significantly different allele frequencies in discovery and validation cohorts. (XLSX 8Â kb

Additional file 4: of Genetic association and stress mediated down-regulation in trabecular meshwork implicates MPP7 as a novel candidate gene in primary open angle glaucoma

Contains figure representing manhattan plot of discovery cohort. The plot was generated from the logistic regression p-values (adjusted for population stratification) of 5,21,873 autosomal SNPs for 347 cases and 354 controls in discovery cohort. p-value of 10â3, taken as threshold for selection of SNPs for validation. The topmost signal is rs1294092 which was not validated in the independent validation stage. (TIF 175Â kb

Additional file 6: of Genetic association and stress mediated down-regulation in trabecular meshwork implicates MPP7 as a novel candidate gene in primary open angle glaucoma

https://figshare.com/articles/Additional_file_3_of_Genetic_association_and_stress_mediated_down-regulation_in_trabecular_meshwork_implicates_MPP7_as_a_novel_candidate_gene_in_primary_open_angle_glaucoma/4366796

Additional file 11: of Genetic association and stress mediated down-regulation in trabecular meshwork implicates MPP7 as a novel candidate gene in primary open angle glaucoma

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University of Salford Institutional Repository

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