Myopia

Myopia (nearsightedness) is already one of the most common conditions covered on this site. A 2016 systematic review and meta-analysis of 145 studies covering 2.1 million people estimated 22.9% of the world's population was myopic in 2000 (1,406 million people), with 2.7% having high myopia (163 million). The same analysis projected those figures would reach 49.8% and 9.8% by 2050 — 4,758 million and 938 million people.

Two ordinary GWAS hits, and one much stranger mechanism

Genome-wide association studies have found dozens of common variants linked to myopia risk, each with a small individual effect — rs9318086 near MIPEP and rs6469937 near SNTB1 are two of them. Identified markers collectively explain only a modest share of the heritability, and none of them changes how myopia is diagnosed or corrected.

A different, more mechanistically striking story comes from the OPN1LW and OPN1MW genes — the long- and middle-wavelength cone opsins, sitting in a tandem array at Xq28. A 2022 study of 413 men of European ancestry found that specific combinations of eight coding positions in OPN1LW's exon 3 — a haplotype, not a single variant — determine how often that exon gets skipped during splicing. Cones expressing an exon-3-skipped transcript are left nearly empty of photopigment. Mean refraction across the eleven haplotypes tested ranged from +0.51 diopters (haplotype MVAIS, the least myopic) to -3.14 diopters (haplotype MVVVA, the most myopic) — a roughly 3.6-diopter spread from haplotype alone. rs145009674, one of the eight defining positions, is included on this site as a way into that finding, not as a variant that alone explains it.

The hypothesis this generates is genuinely testable: cones next to each other with very different amounts of photopigment would send a distorted contrast signal, and that distortion — not blur itself — might be what drives the eye's axial elongation in myopia. The same research group is testing contrast-reducing spectacle lenses in a multi-center randomized trial of 256 participants; a 12-month interim analysis favored the contrast-reducing lenses over standard correction.

Where near-work habits enter the genetics

Fan et al. 2016 (CREAM Consortium) analysed 50,351 people — 40,036 of European ancestry and 10,315 of Asian ancestry, across 34 studies — using a model that jointly tests an ordinary genetic effect on refractive error alongside how that effect might change with a person's education level, used here as a proxy for a lifetime of near-work: reading and close-up focus are thought to induce a lag in visual accommodation that promotes the eye elongation behind myopia.

The joint test found nine new loci for refractive error — six in the European analysis, three in the Asian analysis. Only the three Asian loci showed a real, statistically significant interaction with education specifically; the study states plainly that the six European loci reached significance through the same joint statistical test but did not actually show an education interaction on closer inspection — their effect on refractive error was constant regardless of educational history. Where an interaction was real, it was substantial: about four times larger on average in the Asian cohort than the European one. rs12511037, near AREG, is one of this page's ten variants from that Asian, education-interacting set.

The other nine variants on this page come from the same combined analysis, spanning both its newly discovered loci and refractive-error signals it reconfirmed from earlier research — not every one individually tested for or shown to carry an education interaction the way AREG was.

Why colour vision deficiency does not get its own page

OPN1LW and OPN1MW are also the genes behind red-green colour vision deficiency, affecting up to 8% of men and 0.5% of women of European descent — the X-linked recessive pattern is why men, with only one X chromosome, are affected so much more often. But the classic cause of colour blindness is a different kind of change entirely: whole-gene deletions or hybrid genes formed when the two near-identical genes recombine unequally with each other. That is a structural rearrangement, not a single-nucleotide variant, and it has no entry in the GWAS Catalog at all. This site's variant pages are built around single positions with a stable rsID, so colour vision deficiency is described here in prose, on the strength of the same gene family covered above, rather than forced onto a variant that does not represent it.