April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
Genome-wide analysis for loci associated with the bilaterality of age-related macular degeneration
Author Affiliations & Notes
  • Kyoko Kumagai
    Ophthalmology, Kyoto University, Kyoto, Japan
  • Kenji Yamashiro
    Ophthalmology, Kyoto University, Kyoto, Japan
  • Masahiro Miyake
    Ophthalmology, Kyoto University, Kyoto, Japan
  • Munemitsu Yoshikawa
    Ophthalmology, Kyoto University, Kyoto, Japan
  • Isao Nakata
    Ophthalmology, Kyoto University, Kyoto, Japan
  • Yumiko Akagi-Kurashige
    Ophthalmology, Kyoto University, Kyoto, Japan
  • Akitaka Tsujikawa
    Ophthalmology, Kyoto University, Kyoto, Japan
  • Ching-Yu Cheng
    Singapore Eye Research Institute, Singapore, Singapore
    Ophthalmology, National University of Singapore and National University Health System, Singapore, Singapore
  • Chiea chuen Khor
    Human Genetics, Genome Institute of Singapore, Singapore, Singapore
  • Nagahisa Yoshimura
    Ophthalmology, Kyoto University, Kyoto, Japan
  • Footnotes
    Commercial Relationships Kyoko Kumagai, None; Kenji Yamashiro, None; Masahiro Miyake, None; Munemitsu Yoshikawa, None; Isao Nakata, None; Yumiko Akagi-Kurashige, None; Akitaka Tsujikawa, None; Ching-Yu Cheng, None; Chiea chuen Khor, None; Nagahisa Yoshimura, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 2219. doi:
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      Kyoko Kumagai, Kenji Yamashiro, Masahiro Miyake, Munemitsu Yoshikawa, Isao Nakata, Yumiko Akagi-Kurashige, Akitaka Tsujikawa, Ching-Yu Cheng, Chiea chuen Khor, Nagahisa Yoshimura; Genome-wide analysis for loci associated with the bilaterality of age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2219.

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

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Purpose: Age-related macular degeneration (AMD) is one of the major irreversible vision-threatening diseases in developed countries. Especially, occurrence of AMD in both eyes cause extreme impairment of the quality of life. Previous studies examined the associations between the bilaterality of AMD and polymorphisms in AMD susceptibility genes such as ARMS2/HTRA1, CFH, C3, and CFB, and ARMS2/ HTRA1 and CFH were reported to contribute to the bilaterality. To reveal the more genetic determinants associated with bilateral AMD, we performed genome-wide association study (GWAS).

Methods: Case-control study was performed between unilateral and bilateral exudative AMD cases in Japanese. Unilateral or bilateral AMD was determined at the final visit. In discovery study, 831 unilateral and 313 bilateral cases were used to conduct GWAS. In the replication analysis, 134 unilateral and 36 bilateral cases were included. 2,370,000 single nucleotide polymorphisms (SNPs) or 730,000 SNPs were genotyped using HumanOmni2.5 chips or HumanOmniExpress BeadChips. Genotype distributions of the SNPs were compared adjusting for age and sex.

Results: In the discovery study, 3 SNPs near LOC646935 and 1 SNP near LOC646936 showed p-value less than 10-6. Furthermore, 10 SNPs showed p-value less than 10-5; 3 SNPs near LOC646935, 2 SNPs near FLJ38725, 2 SNPs in CTNNA3, 1 SNP in HTRA1, 1 SNP in LHFP and 1 SNP in PLXNA1. Of the each top SNPs of 6 loci examined in the replication study, rs4482537 near LOC646935 (P = 4.97 × 10-2), rs2284665 in HTRA1(P = 3.83 × 10-2), and rs8002574 in LHFP (P = 3.66 × 10-2) were confirmed to have significant association to the bilaterality. The pooled study further confirmed significant association of LOC646935 (rs4482537; P = 2.06 × 10-8), HTRA1 (rs2284665; P = 3.22 × 10-7), and LHFP (rs8002574; P = 3.91 × 10-7) with the odds ratio of 1.73 (95%CI; 1.43 - 2.10), 0.62 (95%CI; 0.51 - 0.74), and 0.40 (95%CI; 0.28 - 0.57), respectively.

Conclusions: Our GWAS confirmed associations of ARMS2/HTRA1 to the bilaterality of exudative AMD, and newly identified association of LOC646935 on chromosome 2 and LHFP on chromosome 13 with the bilaterality in Japanese population.

Keywords: 412 age-related macular degeneration • 539 genetics • 537 gene screening  

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