Rare genetic variation in PTPRB is associated with central serous chorioretinopathy, varicose veins and glaucoma
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 poten...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58686-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850284672087490560 |
|---|---|
| author | Joel T. Rämö Bryan R. Gorman Lu-Chen Weng Sean J. Jurgens Panisa Singhanetr Marisa G. Tieger Elon HC van Dijk Christopher W. Halladay Xin Wang Blake M. Hauser Soo Hyun Kim Joost Brinks Seung Hoan Choi Yuyang Luo FinnGen VA Million Veteran Program 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 Elizabeth J. Rossin |
| author_facet | Joel T. Rämö Bryan R. Gorman Lu-Chen Weng Sean J. Jurgens Panisa Singhanetr Marisa G. Tieger Elon HC van Dijk Christopher W. Halladay Xin Wang Blake M. Hauser Soo Hyun Kim Joost Brinks Seung Hoan Choi Yuyang Luo FinnGen VA Million Veteran Program 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 Elizabeth J. Rossin |
| author_sort | Joel T. Rämö |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e5a866fcde8c4fd0b8a917aef0f72ace |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e5a866fcde8c4fd0b8a917aef0f72ace2025-08-20T01:47:29ZengNature PortfolioNature Communications2041-17232025-05-0116111310.1038/s41467-025-58686-6Rare genetic variation in PTPRB is associated with central serous chorioretinopathy, varicose veins and glaucomaJoel T. Rämö0Bryan R. Gorman1Lu-Chen Weng2Sean J. Jurgens3Panisa Singhanetr4Marisa G. Tieger5Elon HC van Dijk6Christopher W. Halladay7Xin Wang8Blake M. Hauser9Soo Hyun Kim10Joost Brinks11Seung Hoan Choi12Yuyang Luo13FinnGenVA Million Veteran ProgramSaiju Pyarajan14Cari L. Nealon15Michael B. Gorin16Wen-Chih Wu17Scott A. Anthony18David P. Roncone19Lucia Sobrin20Kai Kaarniranta21Suzanne Yzer22Aarno Palotie23Neal S. Peachey24Joni A. Turunen25Camiel JF Boon26Patrick T. Ellinor27Sudha K. Iyengar28Mark J. Daly29Elizabeth J. Rossin30Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of HelsinkiCenter for Data and Computational Sciences (C-DACS), VA Cooperative Studies Program, VA Boston Healthcare SystemCardiovascular Disease Initiative, Broad Institute of MIT and HarvardCardiovascular Disease Initiative, Broad Institute of MIT and HarvardMassachusetts Eye and EarNew England Eye Center, Tufts Medical CenterDepartment of Ophthalmology, Leiden University Medical CenterCenter of Innovation in Long Term Services and Supports, Providence VA Medical CenterCardiovascular Disease Initiative, Broad Institute of MIT and HarvardMassachusetts Eye and EarMassachusetts Eye and EarDepartment of Ophthalmology, Leiden University Medical CenterDepartment of Biostatistics, Boston UniversityMassachusetts Eye and EarVA Cooperative Studies Program, VA Boston Healthcare SystemEye Clinic, VA Northeast Ohio Healthcare SystemDepartment of Ophthalmology, David Geffen School of Medicine, Stein Eye Institute, University of California, Los AngelesSection of Cardiology, Medical Service, VA Providence Healthcare SystemEye Clinic, VA Northeast Ohio Healthcare SystemEye Clinic, VA Northeast Ohio Healthcare SystemHarvard Medical School Department of Ophthalmology, Massachusetts Eye and EarDepartment of Ophthalmology, University of Eastern Finland and Kuopio University HospitalDepartment of Ophthalmology, Radboud University Medical CenterInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of HelsinkiResearch Service, VA Northeast Ohio Healthcare SystemFolkhälsan Research Center, BiomedicumDepartment of Ophthalmology, Leiden University Medical CenterCardiovascular Disease Initiative, Broad Institute of MIT and HarvardResearch Service, VA Northeast Ohio Healthcare SystemInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of HelsinkiHarvard Medical School Department of Ophthalmology, Massachusetts Eye and EarAbstract 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.https://doi.org/10.1038/s41467-025-58686-6 |
| spellingShingle | Joel T. Rämö Bryan R. Gorman Lu-Chen Weng Sean J. Jurgens Panisa Singhanetr Marisa G. Tieger Elon HC van Dijk Christopher W. Halladay Xin Wang Blake M. Hauser Soo Hyun Kim Joost Brinks Seung Hoan Choi Yuyang Luo FinnGen VA Million Veteran Program 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 Elizabeth J. Rossin Rare genetic variation in PTPRB is associated with central serous chorioretinopathy, varicose veins and glaucoma Nature Communications |
| title | Rare genetic variation in PTPRB is associated with central serous chorioretinopathy, varicose veins and glaucoma |
| title_full | Rare genetic variation in PTPRB is associated with central serous chorioretinopathy, varicose veins and glaucoma |
| title_fullStr | Rare genetic variation in PTPRB is associated with central serous chorioretinopathy, varicose veins and glaucoma |
| title_full_unstemmed | Rare genetic variation in PTPRB is associated with central serous chorioretinopathy, varicose veins and glaucoma |
| title_short | Rare genetic variation in PTPRB is associated with central serous chorioretinopathy, varicose veins and glaucoma |
| title_sort | rare genetic variation in ptprb is associated with central serous chorioretinopathy varicose veins and glaucoma |
| url | https://doi.org/10.1038/s41467-025-58686-6 |
| work_keys_str_mv | AT joeltramo raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT bryanrgorman raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT luchenweng raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT seanjjurgens raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT panisasinghanetr raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT marisagtieger raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT elonhcvandijk raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT christopherwhalladay raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT xinwang raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT blakemhauser raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT soohyunkim raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT joostbrinks raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT seunghoanchoi raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT yuyangluo raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT finngen raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT vamillionveteranprogram raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT saijupyarajan raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT carilnealon raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT michaelbgorin raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT wenchihwu raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT scottaanthony raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT davidproncone raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT luciasobrin raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT kaikaarniranta raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT suzanneyzer raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT aarnopalotie raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT nealspeachey raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT joniaturunen raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT camieljfboon raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT patricktellinor raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT sudhakiyengar raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT markjdaly raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma AT elizabethjrossin raregeneticvariationinptprbisassociatedwithcentralserouschorioretinopathyvaricoseveinsandglaucoma |