A genomewide association study on individuals with occludable angles identifies potential risk loci for intraocular pressure

Sudipta Chakraborty, Anshul Sharma, Indranil Bagchi, Soumen Pal, Chandrika Bhattacharyya, Viney Gupta, Arindam Maitra, Samsiddhi Bhattacharjee, Arundhati Sharma, Ramanjit Sihota, Moulinath Acharya

Research output: Contribution to journalArticlepeer-review

Abstract

Glaucoma is a heterogeneous group of optic neuropathies and is one of the leading causes of irreversible blindness worldwide. Primary angle closure glaucoma (PACG) is a major subtype, prevalent mostly in east and south Asia, where occludable anterior chamber angle is considered as a primary risk factor, which in turn could be responsible for high intraocular pressure (IOP) and subsequent neurodegeneration of retinal ganglion cells. Clinically, IOP is considered as a major risk factor for glaucoma and viewed as an important endophenotype to promote the disease severity. To investigate the comprehensive genomic insights, we conducted a genomewide association study (GWAS) on IOP in individuals with occludable angle (< 15 degrees), thus anatomically predisposed to PACG. After performing GWAS on IOP, we identified 25 genomewide suggestive significant loci (P < 1e−05, n = 240) of which, six were in complete linkage disequilibrium with the ABCA4 genic region. We successfully replicated the most significant discovery, SNPs of ABCA4 (rs2065712) in a separate cohort of 89 individuals (P =1.16e−09). We identified multiple SNPs in ABCA4 to be associated with IOP. Also, we obtained genes harbouring significantly associated SNPs, included in relevant biological pathways that could potentially be involved in IOP variation and glaucomatous neurodegeneration.

Original languageEnglish (US)
Article number69
JournalJournal of genetics
Volume100
Issue number2
DOIs
StatePublished - Oct 2021
Externally publishedYes

Keywords

  • ABCA4 gene
  • bioinformatics
  • intraocular pressure
  • occludable anterior chamber angle
  • quantitative trait genomewide association study
  • taqman assay

ASJC Scopus subject areas

  • Genetics

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