Crandall, & Atzmon, 2010). Not all investigations of genetic resistance in subjects at-risk for but without disease have yielded similar successes. For example, recently a genome sequencing study of 454 “wellderly” subjects over 80 with no chronic disease, failed to identify protective variants (Erikson et al., 2016). Thus, a framework for investigating genetic resistance is needed to avoid further reliance on serendipitous discovery or secondary analyses in samples not ascertained to study resistance. The need for innovative study design is more pronounced in prevention trials, where the use of random samples of hundreds of thousands of subjects to identify tens of resistant subjects is infeasible.
