July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Post-GWAS analysis on the molecular machinery in refractive error development
Author Affiliations & Notes
  • Milly S. Tedja
    Ophthalmology & Epidemiology, Erasmus MC, Rotterdam, Netherlands
  • Robert Wojciechowski
    Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Pirro G Hysi
    Twin Research and Genetic Epidemiology, King’s College London School of Medicine, London, United Kingdom
  • Virginie JM Verhoeven
    Ophthalmology & Epidemiology, Erasmus MC, Rotterdam, Netherlands
  • Christopher J Hammond
    Ophthalmology, King’s College London School of Medicine, London, United Kingdom
  • Caroline C W Klaver
    Ophthalmology & Epidemiology, Erasmus MC, Rotterdam, Netherlands
    Ophthalmology, Radboud University Medical Center, Nijmegen, Netherlands
  • Footnotes
    Commercial Relationships   Milly Tedja, None; Robert Wojciechowski, None; Pirro Hysi, None; Virginie Verhoeven, None; Christopher Hammond, None; Caroline Klaver, None
  • Footnotes
    Support  ERC MYOP-PATH
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1821. doi:
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    • Get Citation

      Milly S. Tedja, Robert Wojciechowski, Pirro G Hysi, Virginie JM Verhoeven, Christopher J Hammond, Caroline C W Klaver; Post-GWAS analysis on the molecular machinery in refractive error development. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1821.

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

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Purpose : Myopia is a complex genetic trait. A recent large GWAS meta-analysis on refractive error (RE) of CREAM and 23andMe (N=160,420) yielded 134 independent associated loci and found light processing to be a key player in myopiagenesis through pathway analyses. Despite all efforts, the molecular machinery behind key pathways remain largely unknown. Using post-GWAS analyses, we now investigate the molecular machinery and pathways behind the genetics of refractive error development.

Methods : We performed a post-GWAS gene-set and pathway analysis using Magma and FUMA tofind new pathways and additional evidence for light dependent pathways. Furthermore, we investigated chromatin structures and transcription factor binding sites in or near associated loci with FUMA.

Results : Gene-set analysis showed significance in 15 gene sets, with eye development (PBonferroni = 2.84e-5) as highest association. Pathway analysis showed significance in > 50 pathways; highlights include the synaptic transmission (“neuronal system”, Padjusted = 1.98e-4; “transmission across chemical synapses”, Padjusted = 9.33e-4), circadian rhythm related genes (Padjusted = 2.81e-3 and matrisome pathway (Padjusted = 4.93e-3). 31 transcription factor binding sites were enriched (Padjusted range: 1.95e-8 – 0.049) and circos plots show complex intrachromosomal chromatin interactions and eQTL information for all index variants of the GWAS meta-analysis.

Conclusions : Our study underlines previously proposed light dependent pathways and indicates regulatory mechanisms interesting for future in-depth methylation analysis in myopiagenesis.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.


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