Research suggests "mosaic" of gene defects 'boosts fat in blood'
Together they raise the risk of harmful amounts of triglycerides, which like the "bad" form of cholesterol are linked to heart disease and strokes.
Very high levels of the fatty substances lead to a disease called hypertriglyceridoemia (HTG).
As well as endangering the heart, the condition is also associated with obesity, diabetes and pancreatitis.
Researchers writing in the journal Nature Genetics today showed that a combination of several genetic faults significantly increased people's risk of the disease.
Two different techniques were used to uncover the genetic basis of HTG in more than 500 patients. One was based on DNA microarrays, or "gene chips" that home in on known common genetic mutations.
The other involved sweeping the whole genetic code for evidence of previously unknown rare variants associated with disease.
The four genes, APOA5, GCKR, LPL and APOB, influence levels of lipids - fatty molecules - in the blood.
Several common and rare mutations were identified that appeared to affect the genes and were related to having HTG.
The rare variants together were found in 28 per cent of HTG patients - about twice the rate seen in healthy individuals.
Study leader Dr Robert Hegele, from the University of Western Ontario in Canada, said: "It's instructive that one single gene is not solely responsible for high triglyceride levels, but rather a mosaic of both common and rare variations in several genes.
"It means that to get a full picture of a patient's genetic risk, you need to consider both common and rare variants in many genes simultaneously, and to use methods that will detect both types of variation."