The true debate over the source of genetic variation for disease is not one of “is it rare or common variants”, or even of “how much does each class contribute”, but rather “how do they work together” 111. An interesting thought experiment is to ask whether a population of individuals who are only polymorphic for common variants differ in their common disease risk; or conversely whether rare variants are sufficient to explain the observed distribution of risk in the absence of common variants. The result of both experiments is likely to be negative, but the challenge is to devise strategies to test the hypotheses.
