Found: the gene that causes short sight: now experts say condition could be halted by eye drops

The above was a headline (13^th September, 2010) from the UK tabloid The Daily Mail a well known arbiter of rationalism and restraint. To be fair to the Mail, the story was picked up by most of the UK media and tagged with similarly lurid headlines. E.g. “Short-sightedness gene discovery could consign glasses to history” from the Telegraph. And it was not just the UK press. The story had gone global: “Rogue gene causes short-sightedness” (Times of India), “Gene for nearsightedness found; treatment could eliminate need for eyeglasses, contact lenses” (New York Daily News). “Australian discovery of myopia gene link” (Sydney Morning Herald).

The headlines, I am afraid, are rather far from the truth as usual. Indeed, if one reads further into these articles you eventually get to the quotes from the poor scientists involved, caught between a desire to publicise their research while at the same time issuing a plaintive bleat for the facts.

The story originates with two papers published in Nature Genetics Hysi PG, Young TL, Mackey DA et al. A genome-wide association study for myopia and refractive error identifies a susceptibility locus at 15q25. Nature Genetics, 12 September 2010

Solouki AM, Verhoeven VJM, van Duijn CM et al. A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14. Nature Genetics, 12 September 2010

Both studies used DNA microarray technology to identify variations in DNA sequences amongst thousands of individuals. The idea is simple. Each cohort consists of individuals who are short sighted, those who are long sighted and those who have no sight defects. Thousands of positions of known DNA sequence variability known as single nucleotide polymorphisms – that is a change at a single letter of the DNA sequence - across the whole genome of each individual were analysed. Statistics was then used to identify DNA variants that are strongly associated with defective eyesight. The two studies identified different DNA variants, but in both cases the variations were close to genes that are known to be expressed strongly in eye tissues and in one case have been shown to be necessary for normal lens formation in mice eyes. Hence the headlines compelling us to believe that ‘the gene’ for short-sightedness has been discovered.

Even the most cursory reading of the above paragraph should reveal the fallacy of these headlines. The two studies identified different variants. So already, we know that there is more than one DNA variant involved in eyesight defects. In fact, variations near three different genes were identified. The second more fundamental issue is that variations in these genes do not cause sight defect in all individuals. In fact the effect is surprisingly small.  For example, individuals with the variant rs8027411 were only 1.16 times more likely to have myopia than no eye problems. So even if gene therapy was routine and it was possible to administer a magic eye drop that would fix the ‘bad’ DNA variant (conservative estimates reckon it will be at least ten years before such a treatment is possible) then the patients’ risk of developing eye problems would decrease by only 16%.

The problem is that the genetic component of vision defects seems to be swamped by environmental effects. In modern society short-sightedness is on the rise. In some parts of Asia, the incidence of myopia has reached extraordinary levels. Nowhere is this more so than in Singapore where 80% of 18-year old army recruits are now short sighted (up from 25% just 30 years ago). And before you Westerners get complacent, this is not some sort of genetic pre-disposition in the Asian population. For example, Ian Morgan and Kathryn Rose of the Australian National University show in their paper “How genetic is school myopia?” published in Progress in Retinal and Eye Research, 24 (2005) 1-38, that 70% of men of Indian origin living in Singapore are short sighted, even though the incidence of short sightedness in India itself is only 10%.

There is little doubt as to the cause. Too much time spent focused on close objects, the computer screen probably being the biggest evil. Light reaching the eye from a near source has to be bent more to bring it into focus on the retina. The eye compensates by growing longer so that the muscles of the lens have to work less hard. The problem then comes when you look up across the room and try to bring something from further away into focus. These more parallel waves of light fall into focus in front of the retina in the long eye. You are now short sighted. In countries like Singapore, a particularly reading-intensive school programme is thought to be behind the high incidence of short sightedness, the still developing eye the most likely to grow longer.

The solution appears to be simple. As Terri Young of Duke University Medical Center (a lead author of one of the Nature Genetics papers) said in a Duke University press release: “People need to go outside and look at the horizon”. Rather makes you wonder why they spent thousands of dollars doing all that genome analysis, doesn’t it?