June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Identification of a novel locus for Exfoliation Syndrome
Author Affiliations & Notes
  • Mineo Ozaki
    Ozaki Eye Hosp, Hyuga, Japan
  • Tin Aung
    Singapore National Eye Center, Singapore, Singapore
  • Takanori Mizoguchi
    Mizoguchi Eye Hosp, Sasebo, Japan
  • R Rand Allingham
    Duke University Eye Center, Durham, NC
  • Robert Ritch
    New York Eye and Ear Infirmary of Mount Sinai, New York, NY
  • Michael A Hauser
    Duke University Medical Center, Durham, NC
  • Chiea Chuen Khor
    Genome Institute of Singapore, Singapore, Singapore
  • Footnotes
    Commercial Relationships Mineo Ozaki, None; Tin Aung, None; Takanori Mizoguchi, None; R Rand Allingham, None; Robert Ritch, None; Michael Hauser, None; Chiea Chuen Khor, None
  • Footnotes
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Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4380. doi:
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      Mineo Ozaki, Tin Aung, Takanori Mizoguchi, R Rand Allingham, Robert Ritch, Michael A Hauser, Chiea Chuen Khor, XFS genetics consortium; Identification of a novel locus for Exfoliation Syndrome. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4380.

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

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Purpose: Exfoliation syndrome (XFS) is an age-related disease, manifesting primarily in the eyes. XFS is a very common and recognizable cause of secondary glaucoma world-wide. We sought to better understand the overall disease process of XFS. To this end, we thus conducted a genome-wide association study (GWAS) on ~1500 patients with XFS matched to ~1200 controls from Japan.

Methods: Genome-wide genotyping was performed using the Illumina OmniExpress beadchip, which assesses >700,000 single nucleotide polymorphisms (SNPs) throughout the human genome. The association between each genetic marker and susceptibility to XFS was measured using logistic regression, contrasting each SNP genotype between XFS patients and controls. The analysis was performed with additional compensation for the top 6 principal components of genetic stratification. We followed up the most significantly associated genetic markers (surpassing P < 1 x 10-4 on primary association analysis) on a further ~7,000 patients and ~20,000 controls from 17 countries.

Results: We observed significant association between a new locus on chromosome 19 and increased susceptibility to XFS (P < 1 x 10-10). Although very strong association at the LOXL1 locus was seen and affirmed, the sentinel SNP marker from the Japanese GWAS discovery set demonstrated strongly opposing directions of the effect allele depending on ethnic grouping (In Japanese: ORA-allele = 10, P = 2 x 10-217; In non-Japanese: ORA-allele = 0.5, P = 2 x 10-31), reminiscent of the previously published LOXL1 rs3825942 and South Africans.

Conclusions: Our findings represent the first genetic locus outside of LOXL1 which surpasses genome-wide significance for XFS, and provides insight into the biology and pathogenesis of the disease.


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