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J Hum Genet. 2017 Dec;62(12):1049-1055. doi: 10.1038/jhg.2017.83. Epub 2017 Aug 24.

Shared genetic variants for polypoidal choroidal vasculopathy and typical neovascular age-related macular degeneration in East Asians.

Author information

Centre for Quantitative Medicine, Duke-NUS Medial School, Singapore, Singapore.
Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore.
Ophthalmology and Visuals Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore.
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Ophthalmology, Seoul National University Bundang Hospital, Gyeonggi, Korea.
National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore, Singapore.
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore.
Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
Department of Ophthalmology, National University of Singapore, Singapore, Singapore.


Polypoidal choroidal vasculopathy (PCV), a subtype of age-related macular degeneration (AMD) more frequently seen in East Asians, has both common and distinct clinical manifestations with typical neovascular AMD (tAMD). We aim to examine the extent to which common genetic variants are shared between these two subtypes. We performed the meta-analysis of association in a total of 1062 PCV patients, 1157 tAMD patients and 5275 controls of East Asian descent from the Genetics of AMD in Asians Consortium at the 34 known AMD loci. A total of eight loci were significantly associated with PCV, including age-related maculopathy susceptibility 2 (ARMS2)-HtrA serine peptidase 1 (HTRA1), complement factor H (CFH), C2-CFB-SKIV2L, CETP, VEGFA, ADAMTS9-AS2 and TGFBR1 (P<5 × 10-4) from the single-nucleotide polymorphism-based test and COL4A3 from the gene-based tests (Pgene=2.02 × 10-4). PCV and tAMD are genetically highly correlated (rg=0.69, P=4.68 × 10-3), with AMD known loci accounting for up to 36% variation. Weaker association for PCV was observed at ARMS2-HTRA1 (Pdif=4.39 × 10-4) and KMT2E-SRPK2(Pdif=4.43 × 10-3), compared with tAMD. Variants at CFH, CETP and VEGFA exhibited different association signals in East Asians, in contrast to those in European individuals. Our data suggest a substantially shared genetic susceptibility for PCV and tAMD, while also highlight the unique associations for PCV, which is useful in understanding the pathogenesis of PCV.

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