Rare genetic variation in PTPRB is associated with central serous chorioretinopathy, varicose veins and glaucoma

Joel T. Rämö, Bryan R. Gorman, Lu-Chen Weng, Sean J. Jurgens, Panisa Singhanetr, Marisa G. Tieger, Elon HC Dijk, Christopher W. Halladay, Xin Wang, Blake M. Hauser, Soo Hyun Kim, Joost Brinks, Seung Hoan Choi, Yuyang Luo, Saiju Pyarajan, Cari L. Nealon, Michael B. Gorin, Wen-Chih Wu, Scott A. Anthony, David P. Roncone, Lucia Sobrin, Kai Kaarniranta, Suzanne Yzer, Aarno Palotie, Neal S. Peachey, Joni A. Turunen, Camiel JF Boon, Patrick T. Ellinor, Sudha K. Iyengar, Mark J. Daly and Elizabeth J. Rossin ()
Additional contact information
Joel T. Rämö: University of Helsinki
Bryan R. Gorman: VA Boston Healthcare System
Lu-Chen Weng: Broad Institute of MIT and Harvard
Sean J. Jurgens: Broad Institute of MIT and Harvard
Panisa Singhanetr: Massachusetts Eye and Ear
Marisa G. Tieger: Tufts Medical Center
Elon HC Dijk: Leiden University Medical Center
Christopher W. Halladay: Providence VA Medical Center
Xin Wang: Broad Institute of MIT and Harvard
Blake M. Hauser: Massachusetts Eye and Ear
Soo Hyun Kim: Massachusetts Eye and Ear
Joost Brinks: Leiden University Medical Center
Seung Hoan Choi: Boston University
Yuyang Luo: Massachusetts Eye and Ear
Saiju Pyarajan: VA Boston Healthcare System
Cari L. Nealon: VA Northeast Ohio Healthcare System
Michael B. Gorin: Los Angeles
Wen-Chih Wu: VA Providence Healthcare System
Scott A. Anthony: VA Northeast Ohio Healthcare System
David P. Roncone: VA Northeast Ohio Healthcare System
Lucia Sobrin: Massachusetts Eye and Ear
Kai Kaarniranta: University of Eastern Finland and Kuopio University Hospital
Suzanne Yzer: Radboud University Medical Center
Aarno Palotie: University of Helsinki
Neal S. Peachey: VA Northeast Ohio Healthcare System
Joni A. Turunen: Biomedicum
Camiel JF Boon: Leiden University Medical Center
Patrick T. Ellinor: Broad Institute of MIT and Harvard
Sudha K. Iyengar: VA Northeast Ohio Healthcare System
Mark J. Daly: University of Helsinki
Elizabeth J. Rossin: Massachusetts Eye and Ear

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Central serous chorioretinopathy is an eye disease characterized by fluid buildup under the central retina whose etiology is not well understood. Abnormal choroidal veins in central serous chorioretinopathy patients have been shown to have similarities with varicose veins. To identify potential mechanisms, we analyzed genotype data from 1,477 patients and 455,449 controls in FinnGen. We identified an association for a low-frequency (allele frequency = 0.5%) missense variant (rs113791087) in PTPRB, the gene encoding vascular endothelial protein tyrosine phosphatase (odds ratio=2.85, P = 4.5 × 10-9). This was confirmed in a meta-analysis of 2,452 patients and 865,767 controls from 4 studies (odds ratio=3.06, P = 7.4 × 10-15). Rs113791087 was associated with a 56% higher prevalence of retinal abnormalities (35.3% vs 22.6%, P = 8.0 × 10-4) in 708 UK Biobank participants and, surprisingly, with increased risk of varicose veins (odds ratio=1.31, P = 2.3 × 10-11) and reduced risk of glaucoma (odds ratio=0.82, P = 6.9 × 10-9). Predicted loss-of-function variants in PTPRB, though rare in number, were associated with central serous chorioretinopathy in All of Us (odds ratio=17.09, P = 0.018). These findings highlight the significance of vascular endothelial protein tyrosine phosphatase in diverse ocular and systemic veno-vascular diseases.

Date: 2025
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DOI: 10.1038/s41467-025-58686-6

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