A genetic variant that once seemed almost guaranteed to cause Crohn disease actually has negligible effects in the general population, a study of more than 43,000 Danish people shows.
The result could be a blow to personalized medicine, which seeks in part to estimate people’s risk of developing diseases by analyzing the genetic variants they carry. Previous studies comparing people with an inflammatory bowel disease called Crohn disease to healthy people have found that people with variations in a gene on chromosome 16 known as NOD2 or CARD15 had 17 times greater risk of developing the disease than people who did not carry the variants.
But the new study, published online April 6 in the Canadian Medical Association Journal, took a different approach. Instead of singling out people with Crohn disease ahead of time, it looked in a general population and found that people carrying a disease-associated variant on both copies of chromosome 16 had only three times greater risk of getting the disease than noncarriers — a rise that is not statistically significant.
“We expected that what we would find would be less in the general population, but not that it would be almost negligible,” says Børge Nordestgaard, a genetic epidemiologist at the University of Copenhagen and leader of the new study.