April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Case-Control Genome-Wide Association Study for Refractive Astigmatism: The CREAM Consortium
Author Affiliations & Notes
  • Claire Simpson
    Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD
  • Qing Li
    Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD
  • Jeremy A Guggenheim
    School of Optometry, Hong Kong Polytechnic University, Honk Kong, China
  • Joan E Bailey-Wilson
    Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD
  • Cathy Williams
    School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
  • Robert Wojciechowski
    Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD
    Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
  • Footnotes
    Commercial Relationships Claire Simpson, None; Qing Li, None; Jeremy Guggenheim, None; Joan Bailey-Wilson, None; Cathy Williams, None; Robert Wojciechowski, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 4510. doi:
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    • Get Citation

      Claire Simpson, Qing Li, Jeremy A Guggenheim, Joan E Bailey-Wilson, Cathy Williams, Robert Wojciechowski, ; Case-Control Genome-Wide Association Study for Refractive Astigmatism: The CREAM Consortium. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4510.

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

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Abstract

Purpose: To identify genetic variants that influence susceptibility to refractive astigmatism in the general population.

Methods: Meta-analyses of genome-wide association studies were carried out for (a) European adults aged at least 25 years old from 21 cohorts, total N=34,589; (b) Asian adults aged at least 25 years old from 7 cohorts, total N=9,295; (c) European youngsters aged <25 years old from 5 cohorts, total N=6,557; (d) the above three samples combined, total N=50,441. Participants were classified as refractive astigmatic cases if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. After genotyping on high-density SNP arrays and imputing using the HapMap-2 reference panel, genome-wide association analysis was carried out using a logistic regression model including terms for age and sex for each cohort separately. Meta analysis was conducted using a fixed effects model.

Results: No marker reached genome-wide significance in any of the meta-analyses. For the European adults the top SNP was rs17795388 (P=7x10E-8) upstream of the neurexin-1 (NRXN1) gene. The top SNPs in the next 4 most strongly associated regions were rs12212674 (P=8x10E-07) within long intergenic non-coding RNA LINC00340, rs7829116 (P=1x10E-06) near COL14A1, rs2871434 (P=2x10E-06) near PCDH7 and rs12607243 (P=3x10E-06) near DSC3. The top SNP in European youngsters was rs6688613 (P=3x10E-06) near MAEL, and in Asian adults was rs7534824 (P=9x10E-07) near LOC101928334. In the meta analysis of all 33 cohorts, the NRXN1 and LINC00340 regions remained the most strongly associated, with rs10086929 (P=2x10E-6) downstream of the TOX gene next.

Conclusions: Two of the genomic regions associated with refractive astigmatism are associated with related ocular traits: SNPs at the TOX gene locus are associated with spherical equivalent refractive error, and SNPs within LINC00340 are associated with corneal curvature. This suggests potential genetic co-susceptibility for these traits (as seen with PDGFRA variants associated with corneal astigmatism, corneal curvature and axial length). Pcdhb9 is differentially expressed in an EGR-1 null mouse myopia model, suggesting potential involvement of the PCDH gene family in refractive development.

Keywords: 428 astigmatism • 539 genetics • 676 refraction  
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