Genome-wide association and multi-omics analyses provide insights into the disease mechanisms of central serous chorioretinopathy

被引：0

作者：

Mori, Yuki ^{[1
,2
]}

van Dijk, Elon H. C. ^{[3
]}

Miyake, Masahiro ^{[1
,2
]}

Hosoda, Yoshikatsu ^{[4
]}

den Hollander, Anneke I. ^{[5
]}

Yzer, Suzanne ^{[6
]}

Miki, Akiko ^{[7
]}

Chen, Li Jia ^{[8
]}

Ahn, Jeeyun ^{[9
,10
]}

Takahashi, Ayako ^{[1
]}

Morino, Kazuya ^{[1
,2
]}

Nakao, Shin-ya ^{[1
,2
]}

Hoyng, Carel B. ^{[6
]}

Ng, Danny S. C. ^{[8
]}

Cen, Ling-Ping ^{[11
]}

Chen, Haoyu ^{[11
]}

Ng, Tsz Kin ^{[11
]}

Pang, Chi Pui ^{[8
,11
]}

Joo, Kwangsic ^{[9
,12
]}

Sato, Takehiro ^{[13
]}

Sakata, Yasuhiko ^{[14
]}

Tajima, Atsushi ^{[13
]}

Tabara, Yasuharu ^{[2
,15
]}

Nagahama Study Grp, Takeo

Park, Kyu Hyung ^{[9
,16
]}

Matsuda, Fumihiko ^{[2
]}

Yamashiro, Kenji ^{[17
]}

Honda, Shigeru ^{[18
]}

Nagasaki, Masao ^{[2
,19
]}

Boon, Camiel J. F. ^{[3
,20
]}

Tsujikawa, Akitaka ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Med, Grad Sch Med, 54 Shogoin Kawahara, Kyoto 6068507, Japan

[2] Kyoto Univ, Ctr Genom Med, Grad Sch Med, Kyoto, Japan

[3] Leiden Univ, Med Ctr, Dept Ophthalmol, Leiden, Netherlands

[4] Hyogo Prefectural Nishinomiya Hosp, Nishinomiya, Japan

[5] Abbvie, Genom Res Ctr, Cambridge, MA 02139 USA

[6] Radboud Univ Nijmegen, Med Ctr, Med Ctr, Nijmegen, Netherlands

[7] Kobe Univ, Dept Surg, Div Ophthalmol, Grad Sch Med, Kobe, Japan

[8] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Peoples R China

[9] Seoul Natl Univ, Pediat, Seoul, South Korea

[10] SMG SNU Boramae Med Ctr, Seoul, South Korea

[11] Joint Shantou Int Eye Ctr Shantou Univ & Chinese U, Shantou, Peoples R China

[12] Seoul Natl Univ, Bundang Hosp, Seongnam, South Korea

[13] Kanazawa Univ, Grad Sch Adv Prevent Med Sci, Dept Bioinformat & Genom, Kanazawa, Japan

[14] Natl Cerebral & Cardiovasc Ctr, Dept Clin Med & Dev, Suita, Osaka, Japan

[15] Shizuoka Grad Univ Publ Hlth, Grad Sch Publ Hlth, Shizuoka, Japan

[16] Seoul Natl Univ Hosp, Seoul, South Korea

[17] Kochi Univ, Kochi Med Sch, Dept Ophthalmol & Visual Sci, Nankoku, Kochi, Kochi 7838505, Japan

[18] Osaka Metropolitan Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Osaka, Japan

[19] Kyushu Univ, Med Inst Bioregulat, Med Res Ctr High Depth Omics, Div Biomed Informat Anal, Fukuoka, Japan

[20] Univ Amsterdam, Dept Ophthalmol, Med Ctr, Amsterdam, Netherlands

来源：

SCIENTIFIC REPORTS | 2025年 / 15卷 / 01期

基金：

美国国家卫生研究院; 日本学术振兴会;

关键词：

GENETIC SUSCEPTIBILITY; VARIANTS; RISK; METAANALYSIS; HAPLOTYPE; ATLAS;

D O I：

10.1038/s41598-025-92210-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Central serous chorioretinopathy (CSC) is a major cause of vision loss, especially in middle-aged men, and its chronic subtype can lead to legal blindness. Despite its clinical importance, the underlying mechanisms of CSC need further clarification. In this study, we conducted a meta-analysis of three genome-wide association studies (GWASs) for CSC consisting of 8811 Asians and Caucasians, followed by replication in an additional 4338 Asians. We identified four genome-wide hits, including a novel hit (rs12960630 at LINC01924-CDH7, Pmeta = 2.97 x 10-9). A phenome-wide association study for rs12960630 showed a positive correlation between its CSC risk allele with plasma cortisol concentration. Expression/splicing quantitative trait loci (QTL) analyses showed an association of all these hits with the expression and/or splicing of genes in genital organs, which may explain the sex differences in CSC. Protein QTL also suggested the protein-level contribution of the complement factor H pathway to CSC pathogenesis.

引用

页数：13

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