Evidence of genetic enrichment for exceptional survival using a family approach: the Leiden Longevity Study.

We conducted a sib pair study in very old subjects for the purpose of mapping longevity loci. In the present analysis, we explore whether our recruitment strategy has resulted in a population enriched for a heritable component for exceptional longevity. Our study includes families with at least two long-living siblings (men aged 89 years or above; women aged 91 years or above). Data were collected on date of birth and, if applicable, date of death of parents, brothers and sisters, offspring, and spouses of the long-living participants. Standardised mortality ratios (SMRs) compared with the general Dutch population, were calculated. The SMR for all siblings of the long-living participants was 0.66 (95% CI 0.60-0.73). A similar survival benefit was also observed in the parents (SMR=0.76, 95% CI 0.66-0.87) and in the offspring of the long-living subjects (SMR=0.65, 95% CI 0.51-0.80). The SMR of the spouses of the long-living subjects was 0.95 (95% CI 0.82-1.12). The familial clustering of extended survival is unlikely to be caused by ascertainment bias, because in all analyses the long-living participants were excluded. Moreover, it is also unlikely to be caused by environmental factors, because the spouses of the long-living participants had a mortality risk comparable with the general Dutch population, whereas they share the same environment. We conclude that our sample is genetically enriched for extreme survival.