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

Author

Listed:
  • Joel T. Rämö

    (University of Helsinki
    Massachusetts Eye and Ear
    Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Bryan R. Gorman

    (VA Boston Healthcare System
    Booz Allen Hamilton)

  • Lu-Chen Weng

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Sean J. Jurgens

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    University of Amsterdam)

  • Panisa Singhanetr

    (Massachusetts Eye and Ear
    Mettapracharak (Wat Rai Khing) Hospital)

  • 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
    Harvard Medical School)

  • Soo Hyun Kim

    (Massachusetts Eye and Ear
    Massachusetts General Hospital
    Harvard Medical School)

  • Joost Brinks

    (Leiden University Medical Center)

  • Seung Hoan Choi

    (Boston University)

  • Yuyang Luo

    (Massachusetts Eye and Ear)

  • Saiju Pyarajan

    (VA Boston Healthcare System
    Brigham and Women’s Hospital and Harvard School of Medicine)

  • Cari L. Nealon

    (VA Northeast Ohio Healthcare System)

  • Michael B. Gorin

    (Los Angeles
    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
    Radboud University Medical Center)

  • Aarno Palotie

    (University of Helsinki
    Massachusetts General Hospital and Harvard Medical School
    Massachusetts General Hospital
    Massachusetts General Hospital and Harvard Medical School)

  • Neal S. Peachey

    (VA Northeast Ohio Healthcare System
    Cleveland Clinic Foundation
    Cleveland Clinic Lerner College of Medicine of Case Western Reserve University)

  • Joni A. Turunen

    (Biomedicum
    University of Helsinki and Helsinki University Hospital)

  • Camiel JF Boon

    (Leiden University Medical Center
    University of Amsterdam)

  • Patrick T. Ellinor

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Sudha K. Iyengar

    (VA Northeast Ohio Healthcare System
    Case Western Reserve University)

  • Mark J. Daly

    (University of Helsinki
    Massachusetts General Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Elizabeth J. Rossin

    (Massachusetts Eye and Ear
    Broad Institute of MIT and Harvard)

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.

Suggested Citation

  • 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 Brin, 2025. "Rare genetic variation in PTPRB is associated with central serous chorioretinopathy, varicose veins and glaucoma," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58686-6
    DOI: 10.1038/s41467-025-58686-6
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