Complicating matters further, numerous rare variants may be detected in a gene or region but they may have disparate effects on phenotype. Common variants have typically been analysed individually 23,48, but with one or two carriers of each rare variant, pooling them using specific criteria becomes attractive47,49,50. Pooling variants of similar class increases the effective MAF of the class and reduces the number of tests performed, but raises several other questions (Box 1).
