Genes and longevity: a genetic-demographic approach reveals sex and age specific gene effects not shown by the case-control approach (APOE and HSP70.1 loci)

Association analyses between genevariability and human longevity carried out bycomparing gene frequencies between populationsamples of different ages (case/control design)may provide information on genes and pathwaysplaying a role in modulating survival at old ages.However, by dealing with cross-sectional data,the gene-frequency (GF) approach ignores cohorteffects in population mortality changes. The genetic-demographic (GD) approach adds demographicinformation to genetic data and allowsthe estimation of hazard rates and survival functionsfor candidate alleles and genotypes. Thusmortality changes in the cohort to which thecross-sectional sample belongs are taken intoaccount. In this work, we applied the GD methodto a dataset relevant to two genes, APOE andHSP70.1, previously shown to be related to longevityby the GF method. We show that the GD method reveals sex- and age-specific allelic effectsnot shown by the GF analysis. In addition, weprovide an algorithm for the implementation of anon-parametric GD analysis.