Rare variant hypothesis for multifactorial inheritance: susceptibility to colorectal adenomas as a model.

The rare variant hypothesis postulates that genetic susceptibility to colorectal neoplasia within the general population is due to a number of low frequency variants in a variety of different genes. Each variant confers a moderate, but detectable, increase in relative risk of developing the disease. Recent evidence suggests that a quarter of patients with multiple adenomatous polyps are due to rare but functionally important variants in just five genes