These results show that a large proportion of genomic regions that harbor one or more rare variants that contribute to disease is likely to create “synthetic” signals of association [6]. If the region carries an excessively large number of causal variants, this expectation decreases, but for intermediate numbers of (causal) rare variants, detection of many such regions appears inevitable due largely to the fact that increasing the number of rare causal variants increases the size of the disease class in that region.
