ArticlePLoS genetics2020
Rare protein-altering variants in ANGPTL7 lower intraocular pressure and protect against glaucoma.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 3 syntheses or guidelines pooled it, 53 citations in OpenAlex.
- Common and rare variant analyses reveal genetic factors underlying idiopathic pulmonary fibrosis and its shared aetiology with severe COVID-19.EBioMedicine · 2025Pooled it
- Rare genetic variation in PTPRB is associated with central serous chorioretinopathy, varicose veins and glaucoma.Nature communications · 2025Pooled it
- Novel ancestry-specific primary open-angle glaucoma loci and shared biology with vascular mechanisms and cell proliferation.Cell reports. Medicine · 2024Pooled it
- GeneSIS: enhancing transferability of polygenic scores with variant-level gene-by-sex interaction effects.bioRxiv : the preprint server for biology · 2026Article
- Blood donor biobank pipeline to collect genome-based samples for research.Scientific reports · 2026Article
- Mechanisms of angiopoietin-like protein 7 regulation and therapeutic potential in tumors.Molecular biology reports · 2026Review
- Angiopoietin-like protein 7: A narrative review and its potential roles in post-myocardial infarction fibrosis.iScience · 2025Review
- Efficient storage and regression computation for population-scale genome sequencing studies.Bioinformatics (Oxford, England) · 2025Article
- Efficient storage and regression computation for population-scale genome sequencing studies.bioRxiv : the preprint server for biology · 2025Article
- Corneal Stromal Stem Cell-Derived Extracellular Vesicles Attenuate ANGPTL7 Expression in the Human Trabecular Meshwork.Translational vision science & technology · 2025Article
- Hypometric genetics: Improved power in genetic discovery by incorporating quality control flags.American journal of human genetics · 2024Article
- Article
- ANGPTL7 and Its Role in IOP and Glaucoma.Investigative ophthalmology & visual science · 2024Article
- Power of inclusion: Enhancing polygenic prediction with admixed individuals.American journal of human genetics · 2023Article
- Integrated Analysis of Transcriptome and Proteome of the Human Cornea and Aqueous Humor Reveal Novel Biomarkers for Corneal Endothelial Cell Dysfunction.International journal of molecular sciences · 2023Article
- Review
- Rare protective variants and glaucoma-relevant cell stressors modulate Angiopoietin-like 7 expression.Human molecular genetics · 2023Article
- Metastasis from the tumor interior and necrotic core formation are regulated by breast cancer-derived angiopoietin-like 7.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- 10 Years of GWAS in intraocular pressure.Frontiers in genetics · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Protein-altering variants that are protective against human disease provide in vivo validation of therapeutic targets. Here we use genotyping data from UK Biobank (n = 337,151 unrelated White British individuals) and FinnGen (n = 176,899) to conduct a search for protein-altering variants conferring lower intraocular pressure (IOP) and protection against glaucoma. Through rare protein-altering variant association analysis, we find a missense variant in ANGPTL7 in UK Biobank (rs28991009, p.Gln175His, MAF = 0.8%, genotyped in 82,253 individuals with measured IOP and an independent set of 4,238 glaucoma patients and 250,660 controls) that significantly lowers IOP (β = -0.53 and -0.67 mmHg for heterozygotes, -3.40 and -2.37 mmHg for homozygotes, P = 5.96 x 10-9 and 1.07 x 10-13 for corneal compensated and Goldman-correlated IOP, respectively) and is associated with 34% reduced risk of glaucoma (P = 0.0062). In FinnGen, we identify an ANGPTL7 missense variant at a greater than 50-fold increased frequency in Finland compared with other populations (rs147660927, p.Arg220Cys, MAF Finland = 4.3%), which was genotyped in 6,537 glaucoma patients and 170,362 controls and is associated with a 29% lower glaucoma risk (P = 1.9 x 10-12 for all glaucoma types and also protection against its subtypes including exfoliation, primary open-angle, and primary angle-closure). We further find three rarer variants in UK Biobank, including a protein-truncating variant, which confer a strong composite lowering of IOP (P = 0.0012 and 0.24 for Goldman-correlated and corneal compensated IOP, respectively), suggesting the protective mechanism likely resides in the loss of interaction or function. Our results support inhibition or down-regulation of ANGPTL7 as a therapeutic strategy for glaucoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.