Cold sores affect around one in five people but, until now, no one has been sure why some are more prone to the virus that causes them.
Researchers at the University of Edinburgh have found people affected by cold sores have a gene mutation, which means their immune system is not able to prevent them from developing.
Cold sores are caused by a strain of the herpes simplex virus - type 1 (HSV-1). Between 80 and 90% of people are infected with the virus, but only a quarter of them get frequent cold sores.
Scientists studied thousands of genes to identify which ones expressed the proteins needed to prevent the virus from becoming active and - as a result - cold sores from developing.
They looked at blood samples from people with cold sores and found one of the genes previously identified - IL28b - was mutated.
This genetic mutation means the body is unable to mount an adequate immune response. The gene is linked to treatment responses for hepatitis C patients. If the gene is mutated, patients are less likely to respond to treatment.
The study, in the journal Plos Pathogens, was funded by the Medical Research Council, the Biotechnology and Biological Sciences Research Council, the Wellcome Trust and the EU.
Professor Juergen Haas, of the University of Edinburgh's Division of Pathway Medicine, said: "Knowing that susceptibility to the virus involved relates to people's genes reinforces the need to research, not only the evolution of viruses themselves, but also the susceptibility of hosts to infection."