LTBP2 gene variants linked to adult glaucoma risk
Carrying one faulty copy of the LTBP2 gene was linked to a fourfold higher risk of adult glaucoma and diagnosis eight years earlier.
Genetics in Medicine
In an observational study of more than 450,000 participants in the UK Biobank, researchers analysed exome sequence data to examine whether carrying single loss-of-function variants in recessive childhood glaucoma genes relates to adult eye disease. They tested three genes: LTBP2, CYP1B1, and CPAMD8. Participants carrying one loss-of-function variant in LTBP2 had an odds ratio of 4.14 for adult-onset primary open-angle glaucoma compared with non-carriers. Glaucoma participants with these LTBP2 variants were diagnosed eight years earlier than those without them. Researchers replicated this association in the All of Us cohort. In contrast, they detected no significant associations for CYP1B1 or CPAMD8. Single-nucleus expression of LTBP2 supported a pathogenic role for extracellular matrix dysfunction in the trabecular meshwork and Schlemm's canal, eye tissues that help drain fluid.
Why it matters
Glaucoma is a leading cause of irreversible vision loss that commonly develops with age. These findings suggest that LTBP2, a gene known to cause recessive childhood glaucoma, also confers an increased risk of adult-onset glaucoma when a person carries a single faulty copy.
Caveats
The observational study evaluated statistical associations between genetic variants and adult-onset disease rather than tracking fluid drainage changes in individuals over time. The findings rely on the UK Biobank and All of Us cohorts.
The paper
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Terri L Young, Elizabeth Rossin, Louis R Pasquale, Pirro G Hysi, Anthony P Khawaja, David A Mackey, Jamie E Craig, Emmanuelle Souzeau, Inas F Aboobakar, Ayellet V Segrè, Janey L Wiggs, UK Biobank Eye,Harvard Medical School
Genetics in Medicine · 8 Oct 2026