Scientific research is about getting answers but sometimes it can also be elegant. Such was the case with an outstanding international research effort led by the Royal College of Surgeons in Ireland (RCSI) and Dublin's Beaumont Hospital.
The study, funded by the Health Research Board (HRB), into the brain disorder Motor Neuron Disease (MND) may help deliver possible new treatments. Yet it also highlights the value and power of looking at the genetics of disease not just on an individual basis but at the level of whole populations.
"Clearly there are some genes that seem to be important in some populations and not in others," explains Dr Orla Hardiman, Beaumont consultant neurologist and RCSI lecturer and epidemiologist. "Population genetics can help to show susceptibility."
For the study, researchers from Ireland, Scotland, England, the US and Sweden pooled their knowledge and records about MND and its genetic causes. It involved close co-operation between Dr Hardiman, Dr Victor Patterson, a consultant neurologist at the Royal Victoria Hospital in Belfast, and Dr Matt Greenway, HRB research fellow at the RCSI.
Their interest focused on a gene called ANG, which produces a protein that encourages the growth of blood vessels. This came from an earlier Scottish study that suggested Celtic populations, including the Irish and the Scots, might be more likely to have mutations in this gene, and as a result be more prone to MND, according to Dr Greenway.
Dr Greenway began a major analysis of 1,600 DNA samples from around the world looking at the ANG gene. Dr Hardiman says the large scale of this study helped to deliver its key findings, which were published this week in the journal Nature Genetics. These included the identification of a novel gene that plays a role in causing the disease and also the fact that mutations of the gene can run in families. "It is actually the biggest study of its kind ever," says Dr Hardiman. "It is unusual to get one as big as this."
Population genetics was an important dimension to this study. "We know that different ethnic groups have different markers in their DNA," explains Dr Hardiman. "These may make a population more prone to getting a disease or resistant to getting a disease."
Being able to look for these susceptibilities has become possible only since the publication of the human genetic code and the development of powerful computer programmes able to sift through this vast store of knowledge. "This wouldn't have been possible five or six years ago," says Dr Hardiman.
Dr Greenway believes population genetics represents a powerful new tool in the fight against disease. The study showed that Celtic populations were more likely to have this MND-related ANG mutation. "It doesn't seem to be important unless you are Irish or Scottish," says Dr Greenway.
The data sets from the US and England delivered a similar result, he adds. "The thing that was unexpected was we saw mutations in all the populations, but all the individuals with the mutation were first- or second-generation Irish or Scottish. Other susceptibility factors have not been found in the Irish but have been found in other ethnic groups."
This should change the way that geneticists look at disease, he believes. Ignoring the ethnicity of a population could distort our understanding of susceptibility in a process he calls the "red sock effect".
"It is like putting a single red sock into a white wash. Everything turns out pink even though there is only one sock," he explains.
California has a diverse population made up mainly of Mexicans, Chinese, Japanese, Africans and Caucasians. If only one group has a disease-susceptibility this can distort assumptions made for the population as a whole, Dr Greenway adds. "It gets diluted down because of the genetic diversity of the entire population."
