PMID- 28835638 OWN - NLM STAT- MEDLINE DCOM- 20180718 LR - 20221207 IS - 1435-232X (Electronic) IS - 1434-5161 (Linking) VI - 62 IP - 12 DP - 2017 Dec TI - Shared genetic variants for polypoidal choroidal vasculopathy and typical neovascular age-related macular degeneration in East Asians. PG - 1049-1055 LID - 10.1038/jhg.2017.83 [doi] AB - 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 x 10(-4)) from the single-nucleotide polymorphism-based test and COL4A3 from the gene-based tests (P(gene)=2.02 x 10(-4)). PCV and tAMD are genetically highly correlated (r(g)=0.69, P=4.68 x 10(-3)), with AMD known loci accounting for up to 36% variation. Weaker association for PCV was observed at ARMS2-HTRA1 (P(dif)=4.39 x 10(-4)) and KMT2E-SRPK2(P(dif)=4.43 x 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. FAU - Fan, Qiao AU - Fan Q AD - Centre for Quantitative Medicine, Duke-NUS Medial School, Singapore, Singapore. FAU - Cheung, Chui Ming Gemmy AU - Cheung CMG AD - Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore. AD - Ophthalmology and Visuals Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore. FAU - Chen, Li Jia AU - Chen LJ AD - Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China. FAU - Yamashiro, Kenji AU - Yamashiro K AUID- ORCID: 0000-0001-9354-8558 AD - Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Ahn, Jeeyun AU - Ahn J AD - Department of Ophthalmology, Seoul National University Bundang Hospital, Gyeonggi, Korea. FAU - Laude, Augustinus AU - Laude A AD - National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore, Singapore. FAU - Mathur, Ranjana AU - Mathur R AD - Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore. AD - Ophthalmology and Visuals Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore. FAU - Mun, Chan Choi AU - Mun CC AD - Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore. FAU - Yeo, Ian Y AU - Yeo IY AD - Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore. FAU - Lim, Tock Han AU - Lim TH AD - National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore, Singapore. FAU - Teo, Yik-Ying AU - Teo YY AD - Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore. AD - Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore. AD - Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore. FAU - Khor, Chiea Chuen AU - Khor CC AUID- ORCID: 0000-0002-1128-4729 AD - Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore. AD - Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore. FAU - Park, Kyu-Hyung AU - Park KH AD - Department of Ophthalmology, Seoul National University Bundang Hospital, Gyeonggi, Korea. FAU - Yoshimura, Nagahisa AU - Yoshimura N AD - Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Pang, Chi Pui AU - Pang CP AD - Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China. FAU - Wong, Tien Yin AU - Wong TY AD - Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore. AD - Ophthalmology and Visuals Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore. AD - Department of Ophthalmology, National University of Singapore, Singapore, Singapore. FAU - Cheng, Ching-Yu AU - Cheng CY AD - Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore. AD - Ophthalmology and Visuals Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore. AD - Department of Ophthalmology, National University of Singapore, Singapore, Singapore. LA - eng PT - Journal Article DEP - 20170824 PL - England TA - J Hum Genet JT - Journal of human genetics JID - 9808008 RN - 0 (CFH protein, human) RN - 80295-65-4 (Complement Factor H) SB - IM MH - Asian People/*genetics MH - Complement Factor H/genetics MH - Genetic Loci/genetics MH - *Genetic Predisposition to Disease MH - *Genetic Variation MH - Humans MH - Macular Degeneration/*genetics MH - Polymorphism, Single Nucleotide/*genetics EDAT- 2017/08/25 06:00 MHDA- 2018/07/19 06:00 CRDT- 2017/08/25 06:00 PHST- 2017/03/15 00:00 [received] PHST- 2017/06/13 00:00 [revised] PHST- 2017/07/20 00:00 [accepted] PHST- 2017/08/25 06:00 [pubmed] PHST- 2018/07/19 06:00 [medline] PHST- 2017/08/25 06:00 [entrez] AID - jhg201783 [pii] AID - 10.1038/jhg.2017.83 [doi] PST - ppublish SO - J Hum Genet. 2017 Dec;62(12):1049-1055. doi: 10.1038/jhg.2017.83. Epub 2017 Aug 24.