Study pinpoints genetic markers for axial length, myopia

Findings may help researchers to develop early intervention strategies, author says.

Genetic research has identified the likely location of genes that help to determine axial length, a key factor in refractive errors such as myopia, according to a study.

Adjusted for age and gender, genetic factors accounted for about 80% of variability axial length values studied, supporting the theory that axial length is hereditary, the authors said.

The study explored underlying factors that influence the development of myopia, David A. Mackey, MD, FRANZCO, the corresponding author, said in a telephone interview with Ocular Surgery News. The findings were published in Ophthalmology.

“This is the first time that myopic researchers have switched from actually looking at myopia itself to looking at its component measures,” Dr. Mackey said. “It would appear that this is a more refined approach to finding the genes for myopia.”

The researchers studied quantitative trait loci influencing axial length, he said.

Genetic factors

Investigators gathered axial length measurements of 893 subjects recruited through the Twin Eye Study in Tasmania and Brisbane Adolescent Twin Study in Australia. The study population comprised 433 pairs of twins (131 pairs of identical twins and 302 pairs of fraternal twins) and 27 non-twin siblings.

“There’s been a lot of debate about genes and environment being involved with the etiology of myopia,” Dr. Mackey said. “We have shown with this study that a large proportion of axial length, and thus myopia, is due to genetic factors, and that was through comparing the concordance of the identical twins to the nonidentical twins.”

Investigators were able to draw on 700 existing genetic markers that had been used in previous studies of the twin population, he said.

“It was the previous research that gave us access to a large number of genetic markers, although in the near future, we’ll have results on a more extensive genome-wide association set of 600,000 markers on the entire Twin Eye Study population,” Dr. Mackey said.

The subjects were mostly normal, with some having minimal refractive errors, not just high myopia, he said.

A genome scan on a subset of 318 subjects from the Brisbane Adolescent Twin Study showed the role that a gene or genes in the chromosome 5q region play in the heritability of axial length, the authors said. The highest linkage peak on chromosome 5q was statistically significant (P = .0004).

“There is a candidate gene in that region that we have investigated, but whether this is actually the cause of that we don’t know yet because we need to do a much larger analysis, not only on the twins but also on other people with myopia and see if this is going to turn out to be the gene involved,” Dr. Mackey said.

Less significant linkages on other chromosomes were also detected, the authors said.

Interventions and further study

Emerging genetic links may yield new strategies for preventing or minimizing myopia, the authors said, adding that environmental factors also affect the development of myopia.

“One of the advantages of twin studies is that you can look at both genetics and environmental factors,” Dr. Mackey said. “Hopefully, we’ll be able to look at the environmental factors that may allow intervention.”

He cited a recent study showing a potential strategy for preventing myopia in children. Genetic research may help to identify children who require intervention, he said.

“Another study by another group in Sydney, Australia … showed that the amount of hours children spent outside was a protective factor for developing myopia,” Dr. Mackey said. “So it may be in the future that we can identify children at risk of myopia and arrange interventions such as getting them to play outside when they’re young [that] may prevent them from developing myopia.”

The quantitative trait loci approach is being used to study other ocular diseases and will become more influential over time, he said.

“This is an approach that’s being used with several eye diseases,” Dr. Mackey said. “We’re also using it for glaucoma. … This method of genetic linkage called quantitative trait loci identification is going to become a more important part of genetic discoveries over the next few years.” – by Matt Hasson

Reference:

Zhu G, Hewitt AW, et al. Genetic dissection of myopia: Evidence for linkage of ocular axial length to chromosome 5q. Ophthalmology. 2008;115:1053-1057.

David A. Mackey, MD, FRANZCO, can be reached at Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, 32 Gisborne St., East Melbourne, Victoria 3002, Australia; +61-3-9929-8713; fax: +61-3-9929-8711; e-mail: dmackey@utas.edu.au.