The common variant common disease hypothesis proposes that genetic susceptibility to common conditions and diseases like hypertension and diabetes is largely due to alleles that have moderate frequency in the population [42]. The ‘rare variant hypothesis’ in contrast, argues that a significant proportion of inherited susceptibility to relatively common chronic diseases is due to the cumulative effects of many low frequency dominantly and independently acting variants of a variety of different genes, and that each of these variants confers a moderate increase in relative disease risk [29]. For many diseases, it is not yet clear which of these hypotheses, or both, will be applicable. Current genome-wide association studies (GWAS) are capable of testing for association with many, even a million, relatively common SNPs, but do not comprehensively test for association with rare variants. Current studies may therefore neglect the effects of this important set of genetic variants [29]. Healthy aging is an uncommon phenotype (we estimate that <12% of individuals born will go on to achieve our definition of healthy aging). Rare variants, with more substantial genetic effects, are generally
