Discovery of Novel Genetic Risk Loci for Acute Central Serous Chorioretinopathy and Genetic Pleiotropic Effect With Age-Related Macular Degeneration.
Discovery of Novel Genetic Risk Loci for Acute Central Serous Chorioretinopathy and Genetic Pleiotropic Effect With Age-Related Macular Degeneration.
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急性中心性浆液性脉络膜视网膜病变的新遗传风险位点的发现以及年龄相关性黄斑变性的遗传多效性效应
DOI：
10.3389/fcell.2021.696885
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发表时间：
2021
影响因子：
5.5
通讯作者：
Ren Y
中科院分区：
文献类型：
--
作者：
Feng L;Chen S;Dai H;Dorajoo R;Liu J;Kong J;Yin X;Ren Y
研究背景中心性浆液性脉络膜视网膜病变（Central serous chorioretinopathy，CSC）是一种严重的异质性脉络膜视网膜病变。CSC和年龄相关性黄斑变性（AMD）之间的共同临床表现以及CFH作为CSC和AMD的遗传风险位点的确认表明两种疾病之间可能存在共同的病理生理机制。方法对464例CSC患者和548名健康对照者的38个AMD相关单核苷酸多态性（single nucleotide polymorphisms，SNPs）进行遗传关联分析，以加深对CSC遗传易感性的认识，并进一步探讨CSC与AMD之间的遗传多效性。结果发现12个SNP与CSC有显著性相关（p < 0.05），1、4和15号染色体上的4个SNP表现出较强的相关性，其证据超过了Bonferroni（BF）校正的显著性[rs 1410996，OR = 1.47，p = 2.37 × 10-5; rs1329428，OR = 1.40，p = 3.32 × 10-4; rs4698775，OR = 1.45，p = 2.20 × 10-4; rs2043085，OR = 1.44，p = 1.91 × 10-4]。虽然rs 1410996和rs 1329428（在已确立的基因座CFH内）的遗传风险效应是相关的（由于高LD），但4号染色体上的rs 4698775和15号染色体上的rs 2043085是CSC的新风险基因座。使用三个独立SNP（rs 1410996、rs 4698775和rs 2043085）构建的多基因风险评分（PRS）显示与CSC高度显著相关（p = 2.10 × 10-7），具有高PRS的前10%受试者的风险是具有最低PRS的后10%受试者的6.39倍。另外还发现3个SNP与CSC患者的临床表现相关。此外，通过比较这38个SNPs在CSC和AMD之间的遗传效应（OR），我们的研究揭示了这两种疾病之间显著但复杂的遗传多效性效应。结论通过发现两个新的遗传风险位点，揭示CSC与AMD之间存在显著的遗传多效性，为阐明遗传组成在CSC发病中的作用提供了新的视角。
Background Central serous chorioretinopathy (CSC) is a severe and heterogeneous chorioretinal disorder. Shared clinical manifestations between CSC and age-related macular degeneration (AMD) and the confirmation of CFH as genetic risk locus for both CSC and AMD suggest possible common pathophysiologic mechanisms between two diseases. Methods To advance the understanding of genetic susceptibility of CSC and further investigate genetic pleiotropy between CSC and AMD, we performed genetic association analysis of 38 AMD-associated single nucleotide polymorphisms (SNPs) in a Chinese CSC cohort, consisting of 464 patients and 548 matched healthy controls. Results Twelve SNPs were found to be associated with CSC at nominal significance (p < 0.05), and four SNPs on chromosomes 1, 4, and 15 showed strong associations whose evidences surpassed Bonferroni (BF)-corrected significance [rs1410996, odds ratios (OR) = 1.47, p = 2.37 × 10–5; rs1329428, OR = 1.40, p = 3.32 × 10–4; rs4698775, OR = 1.45, p = 2.20 × 10–4; and rs2043085, OR = 1.44, p = 1.91 × 10–4]. While the genetic risk effects of rs1410996 and rs1329428 (within the well-established locus CFH) are correlated (due to high LD), rs4698775 on chromosome 4 and rs2043085 on chromosome 15 are novel risk loci for CSC. Polygenetic risk score (PRS) constructed by using three independent SNPs (rs1410996, rs4698775, and rs2043085) showed highly significant association with CSC (p = 2.10 × 10–7), with the top 10% of subjects with high PRS showing 6.39 times higher risk than the bottom 10% of subjects with lowest PRS. Three SNPs were also found to be associated with clinic manifestations of CSC patients. In addition, by comparing the genetic effects (ORs) of these 38 SNPs between CSC and AMD, our study revealed significant, but complex genetic pleiotropic effect between the two diseases. Conclusion By discovering two novel genetic risk loci and revealing significant genetic pleiotropic effect between CSC and AMD, the current study has provided novel insights into the role of genetic composition in the pathogenesis of CSC.
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影响因子：
16.6
作者：
Cheng, Ching-Yu;Yamashiro, Kenji;Chen, Li Jia;Ahn, Jeeyun;Huang, Lulin;Huang, Lvzhen;Cheung, Chui Ming G.;Miyake, Masahiro;Cackett, Peter D.;Yeo, Ian Y.;Laude, Augustinus;Mathur, Ranjana;Pang, Junxiong;Sim, Kar Seng;Koh, Adrian H.;Chen, Peng;Lee, Shu Yen;Wong, Doric;Chan, Choi Mun;Loh, Boon Kwang;Sun, Yaoyao;Davila, Sonia;Nakata, Isao;Nakanishi, Hideo;Akagi-Kurashige, Yumiko;Gotoh, Norimoto;Tsujikawa, Akitaka;Matsuda, Fumihiko;Mori, Keisuke;Yoneya, Shin;Sakurada, Yoichi;Iijima, Hiroyuki;Iida, Tomohiro;Honda, Shigeru;Lai, Timothy Yuk Yau;Tam, Pancy Oi Sin;Chen, Haoyu;Tang, Shibo;Ding, Xiaoyan;Wen, Feng;Lu, Fang;Zhang, Xiongze;Shi, Yi;Zhao, Peiquan;Zhao, Bowen;Sang, Jinghong;Gong, Bo;Dorajoo, Rajkumar;Yuan, Jian-Min;Koh, Woon-Puay;van Dam, Rob M.;Friedlander, Yechiel;Lin, Ying;Hibberd, Martin L.;Foo, Jia Nee;Wang, Ningli;Wong, Chang Hua;Tan, Gavin S.;Park, Sang Jun;Bhargava, Mayuri;Gopal, Lingam;Naing, Thet;Liao, Jiemin;Ong, Peng Guan;Mitchell, Paul;Zhou, Peng;Xie, Xuefeng;Liang, Jinlong;Mei, Junpu;Jin, Xin;Saw, Seang-Mei;Ozaki, Mineo;Mizoguchi, Takanori;Kurimoto, Yasuo;Woo, Se Joon;Chung, Hum;Yu, Hyeong-Gon;Shin, Joo Young;Park, Dong Ho;Kim, In Taek;Chang, Woohyok;Sagong, Min;Lee, Sang-Joon;Kim, Hyun Woong;Lee, Ji Eun;Li, Yi;Liu, Jianjun;Teo, Yik Ying;Heng, Chew Kiat;Lim, Tock Han;Yang, Suk-Kyun;Song, Kyuyoung;Vithana, Eranga N.;Aung, Tin;Bei, Jin Xin;Zeng, Yi Xin;Tai, E. Shyong;Li, Xiao Xin;Yang, Zhenglin;Park, Kyu-Hyung;Pang, Chi Pui;Yoshimura, Nagahisa;Wong, Tien Yin;Khor, Chiea Chuen
通讯作者：
Khor, Chiea Chuen
DOI：
10.1097/iae.0000000000001443
发表时间：
2017-10
期刊：
Retina (Philadelphia, Pa.)
影响因子：
--
作者：
Daruich A;Matet A;Marchionno L;De Azevedo JD;Ambresin A;Mantel I;Behar-Cohen F
通讯作者：
Behar-Cohen F
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
DOI：
10.1097/iae.0b013e3181be0a83
发表时间：
2009-11-01
影响因子：
3.3
作者：
Imamura, Yutaka;Fujiwara, Takamitsu;Spaide, Richard F.
通讯作者：
Spaide, Richard F.
影响因子：
13.7
作者：
de Jong, Eiko K.;Breukink, Myrte B.;Boon, Camiel J. F.
通讯作者：
Boon, Camiel J. F.