A genetic variation doubles the risk of developing calcium deposits in the heart, a common condition that, in severe cases, can narrow or block the aorta.
The genetic variation, found in 7 per cent of the population, provides important clues about how to treat the disease, researchers said in a study published on Wednesday in the New England Journal of Medicine.
"This is an important step forward in understanding the biology of the development of aortic stenosis," said senior author Wendy Post, from the US Johns Hopkins University School of Medicine.
She said the latest findings could lead to the development of targeted medications to slow the progression of the disease, which can cause chest pain and shortness of breath, and can in some cases require surgery.
The gene in question is involved in the production of a type of cholesterol particle called lipoprotein (a), which circulates in the blood.
"Increased levels of lipoprotein (a) have been previously associated with aortic valve disease. However, prior studies could not differentiate whether it was simply a marker or a causal factor," said lead author Catherine Campbell, of Kaiser Permanente.
"Our results provide the first evidence for a causal relationship."
The researchers studied 2.5 million gene variants among more than 6900 people of white European heritage, and they found that the particular variant was strongly associated with the aortic calcium deposits.
The scientists then confirmed the link in studies with three other groups - more than 2000 people of Hispanic origin, about 2500 African-Americans, and more than 700 Germans.
They also demonstrated that the gene variant was linked to a future risk of developing the heart condition, using data from nearly 40,000 people in Sweden and Denmark.
Other risk factors for developing aortic stenosis include advancing age, high blood pressure, obesity, high cholesterol levels and smoking. Men are at higher risk than women.