Abstract
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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Acknowledgements
We gratefully thank all the participants or volunteers who participated in the studies. This study was supported by the National Medical Research Council (NMRC grants 0796/2003, IRG07nov013, IRG09nov014, NMRC 1176/2008, NIG/1003/2009, STaR/0003/2008, CG/SERI/2010 and CSA/033/2012) and Biomedical Research Council (BMRC 08/1/35/19/550, 09/1/35/19/616 and 10/1/35/19/671) in Singapore; Direct Grants of the Chinese University of Hong Kong (4054119, CPP and 2015.1.045, LJC, Hong Kong); BrightFocus Foundation (M2011068), USA; the Seoul National University Bundang Hospital Research Grant Fund (grant number 03-2009-008) and National Research Foundation of Korea (NRF-2009-0072603, NRF-2012R1A1A2008943 and NRF-2014R1A2A1A09005824) grants funded by the Ministry of Education, Science and Technology, Korea; and grants-in-aid for scientific research (number 24249082) from the Japan Society for the Promotion of Science,Tokyo, Japan.
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Fan, Q., Cheung, C., Chen, L. et al. Shared genetic variants for polypoidal choroidal vasculopathy and typical neovascular age-related macular degeneration in East Asians. J Hum Genet 62, 1049–1055 (2017). https://doi.org/10.1038/jhg.2017.83
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DOI: https://doi.org/10.1038/jhg.2017.83
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