Expressive

rs10860882 (IGF1): Eye Pressure and Glaucoma Risk

Key takeaways

  • rs10860882 lies near IGF1 (insulin-like growth factor 1) and LINC00485, a region linked to intraocular pressure and primary open-angle glaucoma
  • Two large GWAS studies involving up to 2.8 million participants identified this locus among hundreds of glaucoma-related risk loci
  • 133 conditionally independent IOP loci collectively explain up to 17% of intraocular pressure variance, a set that includes rs10860882
  • Associations replicated across multiple ancestries, with 240 of 312 discovered loci surviving strict Bonferroni correction in an independent cohort

Key takeaways

  • rs10860882 lies near IGF1 (insulin-like growth factor 1) and LINC00485 (a long non-coding RNA), a genomic region linked to intraocular pressure and primary open-angle glaucoma
  • Two large-scale GWAS studies involving up to 2.8 million participants identified this locus among hundreds of glaucoma-related risk loci
  • 133 conditionally independent IOP loci collectively explain up to 17% of intraocular pressure variance across replication cohorts; rs10860882 is among the significant signals
  • Associations were replicated across multiple ancestries in large independent cohorts, with 240 of 312 discovered loci surviving strict statistical correction

What the research says A multitrait genome-wide association study (MTAG, a method that boosts statistical power by jointly analyzing genetically correlated traits) in over 600,000 European-ancestry participants covering primary open-angle glaucoma (POAG), intraocular pressure (IOP, the fluid pressure inside the eye), and vertical cup-to-disc ratio (VCDR, a structural measure of optic nerve head excavation) identified 263 loci, expanding to 312 in a multiancestry analysis totaling over 2.8 million participants, with the vast majority replicating in an independent cohort. A separate IOP-focused meta-analysis in 139,555 European participants identified 112 genomic loci for IOP, 68 of them novel, with 133 conditionally independent signals collectively explaining 9% of IOP variance in UK Biobank and 17% in EPIC-Norfolk, while 48 of those IOP loci also associated with POAG in an independent cohort.

Reported associations

  • Primary open-angle glaucoma (POAG): This locus is among 312 genome-wide significant signals identified in a multiancestry MTAG analysis; 296 loci replicated at P < 0.05 and 240 passed Bonferroni correction in an independent replication cohort of 84,910 cases and 2,736,075 controls
  • Primary open-angle glaucoma (POAG): In a separate IOP meta-analysis of 139,555 European participants, 48 of 120 significant IOP loci were also independently associated with POAG in a separate cohort, with 14 of those 48 reaching Bonferroni-corrected significance, indicating that many IOP-associated loci mediate glaucoma risk through elevated pressure
  • Intraocular pressure (IOP): This locus is among 112 genome-wide significant IOP signals from a meta-analysis of 139,555 European participants; 133 conditionally independent signals from this analysis explain 9% of IOP variance in UK Biobank and 17% in EPIC-Norfolk; IOP heritability is estimated at 55%
  • Vertical cup-to-disc ratio (VCDR): VCDR was jointly analyzed as an endophenotype alongside POAG and IOP; VCDR is strongly genetically correlated with POAG (genetic correlation 0.50, s.e.m. 0.05) but only modestly correlated with IOP (genetic correlation 0.22, s.e.m. 0.03), suggesting that VCDR signals from this region may capture neuro-protective pathways distinct from pressure-related mechanisms

Evidence quality Both supporting studies rank among the largest glaucoma genetics investigations to date. Prior to these analyses, 127 POAG loci explained only 9.4% of familial glaucoma risk, leaving most heritability unaccounted for. The multitrait study used a European-ancestry discovery phase exceeding 600,000 participants and confirmed findings in an independent 23andMe dataset (2,736,075 controls, 84,910 cases), with 240 of 312 loci surviving Bonferroni correction. The multitrait study also extended findings to Asian (6,935 cases, 39,588 controls) and African (3,281 cases, 2,791 controls) ancestry populations. The IOP meta-analysis applied a genome-wide significance threshold (P < 5x10^-8) across three European cohorts and validated 49 loci in an independent dataset at FDR < 0.05. Both studies are primarily discovery-stage European-ancestry analyses; replication in non-European populations is more limited. No individual effect size specific to rs10860882 was reported in the available study text.

Lifestyle considerations No lifestyle considerations on file for this variant.

Lifestyle context

Concrete actions anchored to the cited research. We do not prescribe, we describe.

Discuss with your doctor

  • Glaucoma screening with ophthalmologist Moderate

    Genetic variants in IGF1-LINC00485 are associated with elevated intraocular pressure and increased glaucoma risk.

    Discuss with ophthalmologist; baseline intraocular pressure measurement recommended

Frequently asked questions

What is rs10860882 associated with?

rs10860882 is a genetic variant near the IGF1 gene and the non-coding RNA LINC00485. It has been identified in large-scale genome-wide studies as associated with intraocular pressure and primary open-angle glaucoma, the most common form of glaucoma.

What does the IGF1 gene do?

IGF1 stands for insulin-like growth factor 1, a protein involved in cell growth and development. The genomic region around IGF1 and the neighboring non-coding RNA LINC00485 has been implicated in the genetics of intraocular pressure and glaucoma in large population-based studies.

Is rs10860882 a glaucoma risk variant?

This variant sits within a locus identified as genome-wide significant for glaucoma and intraocular pressure in studies covering millions of people. It is one of over 300 loci associated with glaucoma-related traits identified to date, most with modest individual effects.

How much does this variant affect intraocular pressure?

No individual effect size for rs10860882 was reported in the available study excerpts. Across the broader set of 133 IOP-linked loci from one large meta-analysis, the combined contribution explains 9% of IOP variance in one cohort and 17% in another.

What is LINC00485?

LINC00485 is a long intergenic non-coding RNA, a type of RNA molecule that does not code for protein but may play regulatory roles in gene expression. It lies adjacent to IGF1 in the genome, and this region has been associated with intraocular pressure and glaucoma risk in large GWAS analyses.