Experience with current genotyping technologies would suggest that rare variants are more difficult to type than SNPs, and thus stringent quality control procedures are required to avoid increased false-positive error rates as a result of genotype misspecification. To increase power, an obvious step would be to combine results of rare variant studies through meta-analysis. Although each study may genotype different loci, we can combine results on the level of the functional unit. This may reduce, or even eliminate, the need for imputation, which may be potentially prone to bias because the spectrum of rare variants is more diverse than that of SNPs, even between populations sharing relatively recent common ancestry, and therefore more difficult to predict [Anderson et al., 2008]. This highlights the need for replication in large samples from closely related populations to confirm rare variant association signals.
