June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Lack of association of primary open angle glaucoma with expansion of the ATXN2 trinucleotide repeat involved in spinocerebellar ataxia 2 and amyotrophic lateral sclerosis
Author Affiliations & Notes
  • Shi Song Rong
    Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
  • Robert Igo
    Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, United States
  • Jessica Cooke Bailey
    Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, United States
    Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, United States
  • Janey L Wiggs
    Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Shi Song Rong, None; Robert Igo, None; Jessica Cooke Bailey, None; Janey Wiggs, None
  • Footnotes
    Support  NIH/NEI R01 EY022305; NIH/NEI P30 EY014104
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1493. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Shi Song Rong, Robert Igo, Jessica Cooke Bailey, Janey L Wiggs; Lack of association of primary open angle glaucoma with expansion of the ATXN2 trinucleotide repeat involved in spinocerebellar ataxia 2 and amyotrophic lateral sclerosis. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1493.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Genome-wide association studies (GWAS) have identified significant association of SNPs located in the ATXN2 genomic region with primary open angle glaucoma (POAG) and intraocular pressure (IOP). The ATXN2 coding sequence includes a CAG repeat that when fully expanded (>34 repeats) causes spinocerebellar ataxia 2, and intermediate expansions (24-34 repeats) contribute to risk of amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. In this study, we investigated this ATXN2 CAG repeat in POAG.

Methods : Fragment analysis was used to size the CAG repeat in 229 POAG cases and 213 controls selected from the NEIGHBORHOOD cohort. The entire repeat genomic region was sequenced using Haloplex next-generation sequencing (NGS) for the 229 POAG cases and 30 controls. SNPs in high LD (linkage disequilibrium)(r2>0.95) with CAG repeats were used to test for association with POAG in the overall NEIGHBORHOOD case control cohort, and for association with POAG and related ocular traits in other published GWAS summary data.

Results : The CAG repeat size ranged from 19 to 27 in POAG cases and from 17 to 27 in controls. Both groups had a mean repeat size of 22, which is the average repeat size in normal populations. Among the 19 different repeat sequences identified by NGS, the most common sequence >22 was a 27 repeat ((CAG)8(CAA)(CAG)4(CAA)(CAG)4(CAA)(CAG)8) with a frequency of 2% in both cases and controls. All other repeats >22 had frequencies of <0.2% in the sequenced individuals. A SNP in high LD (r2>0.95) with the 27 repeat (rs117129118) was not significantly associated with POAG (N=2606 cases, 2606 controls), or high-tension (N=1298) or low-tension glaucoma (N=561) in the NEIGHBORHOOD dataset (P>0.05). In published GWAS summary data, rs117129118 was also not associated with POAG, IOP, CDR, or CCT.

Conclusions : Expansion of the ATXN2 CAG repeat was not associated with POAG in a large case/control cohort suggesting that expansion of the ATXN2 CAG repeat does not alter glaucoma risk. These results suggest that other genetic variants in the ATXN2 locus contribute to POAG risk.

This is a 2021 ARVO Annual Meeting abstract.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×