Smokers, who carry common gene variants, are at a greater risk of aneurysm, a medical condition in which a blood vessel in the brain weakens and balloons out, say researchers.
Researchers reported on two new studies from the Familial Intracranial Aneurysm (FIA) project, to reach the conclusion.
A study had found that the chance of an intracranial aneurysm increased between 37 percent and 48 percent for people who carried one copy of an identified risky gene variation.
However, when the gene variant was combined with smoking the equivalent of one pack a day for 20 years, the risk increased more than five-fold.
And people with two copies of the gene variant were at even higher risk.
Joseph P. Broderick, study author and professor and chair of the neurology department at the University of Cincinnati Neuroscience Institute, mentioned that an estimated 70 percent to 80 percent of people who experience aneurysms are current or former smokers.
He added that in the study, 82.5 percent of participants were smokers at some point.
Broderick said: "Like putting a match to kindling, smoking greatly increases the likelihood of a ruptured aneurysm in people with a genetic susceptibility.
After comparing the frequency in 406 patients from the FIA families with that of 392 control subjects without aneurysm in the Cincinnati area, researchers confirmed that certain gene variants on chromosomes 8 and 9 raise the risk of intracranial aneurysm.
Other variants on chromosome 2, suggested as genetic risks in a prior study on other populations, were not found to be risk factors in this study.
In the study about 22 percent of controls had a least one copy of the gene variant on chromosome 8 and 73 percent had at least one copy of the variant for chromosome 9.
Broderick said: "These results tell us the approximate location of the risk-inducing gene on the chromosomes but does not identify the exact gene or how its functioning contributes to the risk of aneurysm,"
"This is a powerful message to family members of people who have had ruptured aneurysms. Even if you have the gene, you can dramatically affect your risk by not smoking. If you smoke, you are multiplying the effect of the gene."
The research has been presented at the American Stroke Association's International Stroke Conference 2010.