| Title: |
Rare genetic variation in PTPRB is associated with central serous chorioretinopathy, varicose veins and glaucoma |
| Authors: |
FinnGen; VA Million Veteran Program; Rämö, Joel T.; Gorman, Bryan R.; Weng, Lu Chen; Palotie, Aarno; Turunen, Joni A.; Daly, Mark J. |
| Contributors: |
Institute for Molecular Medicine Finland; Genomics of Neurological and Neuropsychiatric Disorders; Complex Disease Genetics; Helsinki Institute of Life Science HiLIFE; HUS Group; Centre of Excellence in Complex Disease Genetics; Research Programs Unit; Aarno Palotie / Principal Investigator; Clinicum; HUS Head and Neck Center; Silmäklinikka |
| Publisher Information: |
Nature Publishing Group |
| Publication Year: |
2025 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
Biomedicine; Genetics; developmental biology; physiology; Health care science; Protein-tyrosine-phosphatase; Ve-ptp; Variants; Stabilizes; Mutations; Biobank; Design; Health; Tie2; Mice |
| Description: |
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. ; Peer reviewed |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISBN: |
978-1-05-004359-9; 1-05-004359-6 |
| Relation: |
We acknowledge funding from the National Institutes of Health and the Research to Prevent Blindness Career Development Award (K12EY016335 and 1K23EY035342) to E.J.R. We acknowledge NIH Core Grant P30EY011373 to the Departments of Ophthalmology at Case Western Reserve University, NIH Core Grant P30EY025585 to Cleveland Clinic School of Medicine at Case Western Reserve University, and unrestricted support from Research to Prevent Blindness to the Departments of Ophthalmology at Case Western Reserve University, Cleveland Clinic School of Medicine at Case Western Reserve University. We acknowledge support from the International Retinal Research Foundation to S.K.I. We want to acknowledge the participants and investigators of FinnGen study. The FinnGen project is funded by two grants from Business Finland (HUS 4685/31/2016 and UH 4386/31/2016) and the following industry partners: AbbVie Inc., AstraZeneca UK Ltd, Biogen MA Inc., Bristol Myers Squibb (and Celgene Corporation & Celgene International II Sarl), Genentech Inc., Merck Sharp & Dohme LCC, Pfizer Inc., GlaxoSmithKline Intellectual Property Development Ltd., Sanofi US Services Inc., Maze Therapeutics Inc., Janssen Biotech Inc, Novartis Pharma AG, and Boehringer Ingelheim International GmbH. Following biobanks are acknowledged for delivering biobank samples to FinnGen: Auria Biobank (www.auria.fi/biopankki), THL Biobank (www.thl.fi/biobank), Helsinki Biobank (www.helsinginbiopankki.fi), Biobank Borealis of Northern Finland (https://www.ppshp.fi/Tutkimus-ja-opetus/Biopankki/Pages/Biobank-Borealis-briefly-in-English.aspx), Finnish Clinical Biobank Tampere (www.tays.fi/en-US/Research_and_development/Finnish_Clinical_Biobank_Tampere), Biobank of Eastern Finland (www.ita-suomenbiopankki.fi/en), Central Finland Biobank (www.ksshp.fi/fi-FI/Potilaalle/Biopankki), Finnish Red Cross Blood Service Biobank (www.veripalvelu.fi/verenluovutus/biopankkitoiminta), Terveystalo Biobank (www.terveystalo.com/fi/Yritystietoa/Terveystalo-Biopankki/Biopankki/) and Arctic Biobank (https://www.oulu.fi/en/university/faculties-and-units/faculty-medicine/northern-finland-birth-cohorts-and-arctic-biobank). All Finnish Biobanks are members of BBMRI.fi infrastructure (www.bbmri.fi). Finnish Biobank Cooperative -FINBB (https://finbb.fi/) is the coordinator of BBMRI-ERIC operations in Finland. We thank the U.S. veteran participants in MVP and MVP staff. This publication does not necessarily represent the views of the U.S. Department of Veterans Affairs or the United States Government. Support from the VA Office of Research & Development is acknowledged by N.S.P. (I01BX003364, I01 BX04557, IK6BX005233). We acknowledge the VA Million Veteran Program (MVP) and the VA-DOE genome-wide PheWAS core analytic team for generating the corresponding PheWAS summary statistics that were used in this manuscript. The All of Us Research Program is supported by the National Institutes of Health, Office of the Director: Regional Medical Centers: 1 OT2 OD026549; 1 OT2 OD026554; 1 OT2 OD026557; 1 OT2 OD026556; 1 OT2 OD026550; 1 OT2 OD 026552; 1 OT2 OD026553; 1 OT2 OD026548; 1 OT2 OD026551; 1 OT2 OD026555; IAA #: AOD 16037; Federally Qualified Health Centers: HHSN 263201600085U; Data and Research Center: 5 U2C OD023196; Biobank: 1 U24 OD023121; The Participant Center: U24 OD023176; Participant Technology Systems Center: 1 U24 OD023163; Communications and Engagement: 3 OT2 OD023205; 3 OT2 OD023206; and Community Partners: 1 OT2 OD025277; 3 OT2 OD025315; 1 OT2 OD025337; 1 OT2 OD025276. In addition, the All of Us Research Program would not be possible without the partnership of its participants. UK Biobank is generously supported by its founding funders the Wellcome Trust and UK Medical Research Council, as well as the British Heart Foundation, Cancer Research UK, Department of Health, Northwest Regional Development Agency and Scottish Government.; https://hdl.handle.net/10138/596160; 105004359639; 001480834000019 |
| Availability: |
https://hdl.handle.net/10138/596160 |
| Rights: |
cc_by_nc_nd ; info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.45C6CC02 |
| Database: |
BASE |