Glaucoma

Glaucoma is not one single disease but a group of eye conditions that damage the optic nerve — the bundle of more than a million nerve fibers that carries visual information from the eye to the brain. Left untreated, that damage causes progressively worsening, permanent vision loss, usually starting at the edges of a person's visual field and, if it continues, closing in toward the center. Glaucoma is a leading cause of irreversible blindness worldwide, and it affects several million people in the United States alone, a number expected to rise substantially as the population ages.

The "Silent Thief of Sight"

Glaucoma has earned that nickname for a genuinely alarming reason: in its most common forms, it typically causes no pain and no noticeable symptoms until a significant amount of vision has already been lost. Peripheral vision fades so gradually, and the brain is so good at filling in the gaps using information from both eyes, that many people don't notice a problem until 40% or more of the relevant nerve fibers have already been damaged. As a result, a substantial share of people living with glaucoma don't yet know they have it — which is precisely why regular comprehensive, dilated eye exams (not just a vision-chart check) matter, especially for people with risk factors such as older age, a family history of glaucoma, or Black, Hispanic/Latino, or East Asian ancestry (each associated with elevated risk for different glaucoma subtypes).

The Main Types

• Primary open-angle glaucoma (POAG) — the most common form, in which fluid drains too slowly from the eye through a drainage angle that looks structurally normal, gradually raising internal eye pressure (intraocular pressure, or IOP) and damaging the optic nerve over months to years.
• Angle-closure glaucoma — less common, occurring when the drainage angle is physically blocked. This can develop gradually or, in an acute attack, very suddenly with severe eye pain, blurred vision, halos around lights, nausea, and redness — a true medical emergency requiring immediate care.
• Normal-tension glaucoma (NTG) — a form of open-angle glaucoma in which the optic nerve is damaged even though measured eye pressure stays within the statistically "normal" range (roughly 10–21 mmHg). It is thought to involve either poor blood flow to the optic nerve or an optic nerve that is unusually vulnerable to damage even at ordinary pressures, and it appears to be relatively more common in some East Asian populations — the population-based Tajimi Study in Japan found most open-angle glaucoma there occurs at normal intraocular pressure — than in populations of European ancestry.
• Congenital and secondary glaucomas — rarer forms present from birth or caused by another eye condition, injury, or medication.

Why Early Detection Is a Genuinely Preventive Story

Unlike some genetic conditions where a variant is simply informative, glaucoma is one of the clearer cases in medicine where early detection changes the outcome. Vision already lost to glaucoma cannot be restored — but with a comprehensive dilated eye exam, optic nerve imaging, and visual field testing, glaucoma can usually be caught well before a person notices any symptoms, and its progression can typically be slowed or halted with prescription eye drops, laser treatment, or surgery to lower eye pressure or otherwise protect the optic nerve. That combination — a disease that causes irreversible damage if ignored, but is genuinely manageable if caught — is exactly why eye care organizations emphasize routine screening, particularly for people with a family history or other risk factors.

The Genetics Discussed on This Page

A specific DNA marker, rs3213787, near a gene called SRBD1, was identified in a 2010 genome-wide genetic study of normal-tension glaucoma conducted by Japanese researchers, where it was associated with a meaningfully higher chance of NTG in that Japanese cohort. As discussed in the clinical detail section below, this finding has held up less consistently when tested in other populations — an important, honest caveat that doesn't diminish the value of understanding one's own genetic background, but does mean this particular marker should be read as a population-level research finding from a specific ancestry group rather than a universal or individually predictive test.

Beyond SRBD1: five more genome-wide studies behind this page

The SRBD1 finding above was the first genetic association held on this page, but it is far from the only one — this page's variants now come from six separate genome-wide studies, spanning intraocular pressure (IOP, the eye-internal fluid pressure that is the main modifiable risk factor for glaucoma) and open-angle glaucoma itself.

Gharahkhani et al. 2014, published back-to-back with a companion IOP study in the same journal issue, found common variants near ABCA1, AFAP1, and GMDS conferring risk of primary open-angle glaucoma (POAG).

That companion paper, Hysi et al. 2014 from the International Glaucoma Genetics Consortium (IGGC), combined 18 cohorts totaling 35,296 multi-ancestry participants studying IOP directly and found four new IOP-associated loci — on chromosome 3q25.31 in FNDC3B, two on chromosome 9 (near ABCA1 and within ABO), and one on chromosome 11p11.2, the strongest of the four. This page's rs747782, in NUP160, is that chromosome-11 locus. A separate case-control analysis of 4,284 POAG cases and 95,560 controls found three of these four IOP loci also associated with glaucoma itself — direct evidence that IOP genetics feeds forward into glaucoma risk, which is why this page holds IOP variants at all rather than treating IOP as a separate trait. 132 of this page's variants come from this study.

Choquet et al. 2018 ran a multiethnic GWAS of POAG (the GERA cohort, replicated in and from UK Biobank) and found 24 significant loci, 14 of them novel, with 9 replicating across cohorts (near FMNL2, PDE7B, TMTC2, IKZF2, CADM2, DGKG, ANKH, EXOC2, and LMX1B). Two of those genes, FMNL2 and LMX1B, had functional follow-up support for an IOP-related role — in mice, certain Lmx1b mutations cause high eye pressure and POAG-like disease. The new loci explained the most additional variance in African-American participants (0.5-3.1%), a population underrepresented in earlier, largely European-ancestry glaucoma genetics.

Khawaja et al. 2018 combined UK Biobank (103,914 participants) with the earlier International Glaucoma Genetics Consortium data (29,578 participants) to study IOP specifically, finding 101 independent genome-wide-significant loci, 85 of them new. 53 of the 101 IOP loci were also associated with glaucoma itself in a separate 11,018-case, 126,069-control analysis — again showing IOP genetics and glaucoma genetics substantially overlap. People in the top decile of a combined allele score built from these loci had 5.6 times the odds of advanced glaucoma compared to the bottom decile.

Craig et al. 2020 took a different approach: rather than studying diagnosed glaucoma directly, the team analyzed optic nerve photographs from 67,040 UK Biobank participants and built a polygenic risk score (PRS) from the resulting loci. That score meaningfully stratifies real-world risk — people in its top decile reach the absolute risk of glaucoma that the bottom decile reaches ten years later, and face roughly 15 times the risk of advanced glaucoma (odds ratio 4.20 for the top 10% versus the rest). The same PRS also modifies how often a specific, well-known glaucoma-causing MYOC variant (p.Gln368Ter) actually goes on to cause disease — a concrete example of polygenic background changing the penetrance of a single strong-effect variant, rather than acting independently of it.

Ramdas et al. 2010 studied a different measurement entirely: the vertical cup-disc ratio (VCDR) — the proportion of the optic disc taken up by its central "cup," the single measurement a clinician actually reads off an eye exam to judge glaucomatous optic nerve damage. In 7,360 people, later replicated in 4,455 more across three further cohorts, the study found CDKN2B and SIX1 genome-wide-significant for VCDR specifically, alongside ATOH7 and CDC7 for a related measurement, optic disc area — and three of its loci were marginally associated with open-angle glaucoma itself. This page's rs2157719 sits in CDKN2B-AS1, the same 9p21 region as the paper's own finding, and rs8015152 sits in SIX6, in the same eye-development gene family as the paper's SIX1. Eleven of this page's variants come from this study.

Khor et al. 2011 ran the first Asian-based GWAS of optic disc area itself — the physical measurement VCDR is a ratio of — in 4,445 Singaporean people, meta-analysed with 9,326 more of Caucasian ancestry from Rotterdam. The study confirmed two known genes, ATOH7 and TGFBR3, and identified a novel locus, CARD10. This page's rs6000762, in CARD10, is the paper's own novel finding. Springelkamp et al. 2017 went further, meta-analysing intraocular pressure alongside optic disc parameters and validating results across multiple POAG case-control sets. It found 9 new regions for VCDR, 1 for intraocular pressure, 5 for optic nerve cup area, and 6 for disc area — and, using a zebrafish model, showed that the zebrafish counterpart of SIX6 alters expression of CDKN1A, a newly identified glaucoma gene. This page's rs34935520, in SIX6, is the same gene that zebrafish experiment validated. Eight of this page's variants come from these two optic-disc-area studies together.

A handful of smaller studies add further loci for specific glaucoma subtypes and populations represented in smaller numbers on this page. The field's largest assembly to date, a 2021 meta-analysis across ancestries (Gharahkhani et al.), found 127 open-angle glaucoma loci with consistent effects. None of this changes the picture above: glaucoma genetics is highly polygenic, no single locus is diagnostic, and a comprehensive eye exam — not a genetic test — remains how glaucoma is actually found and monitored.