In addition to a sequencing technology and an appropriate sampling and study design, bioinformatic methods for analyzing the potentially massive amounts of sequence data likely to be generated in a study are needed, as are algorithms for accurately identifying rare variants and assigning genotypes to individuals from sequence data12, 27. Importantly, statistical analysis methods for relating rare variants to phenotypes of interest are needed. Association analyses involving rare variants are not as straightforward as analyses involving common variations since the power to detect an association between a single rare variant is low in even very large samples (Figure 1).14, 28, 29 Therefore, researchers have begun to develop data analysis strategies that assess the collective effects of multiple rare variants within and across genomic regions 13, 28, 30. This challenge of statistical analysis is the focus of this Review.
