Weighted statistics for aggregation and linkage analysis of human longevity in selected families: the Leiden Longevity Study.

Typically long-lived sibling pairs have been collected for linkage analysis of human longevity and information on life span of first-degree relatives is available to assess familial aggregation of life span. We propose a new weighted statistic for aggregation analysis, which tests for a relationship between a family history of excessive survival of the sibships of the long-lived pairs and the survival of their parents and their offspring. For linkage analysis, we derive a new weighted score statistic from a simple gamma frailty model, which assigns more weight to excessive long-lived pairs. We apply the methods to data from the Leiden Longevity Study, which consists of sibling pairs of age 90 years or above and their first-degree relatives. The pairs have been genotyped for microsatellite markers in a candidate region. Association was present between survival within the sibships and survival of the offspring, but not with the parental generation. For linkage analysis, weighting increased the value of the test statistic, but the result was not statistically significant. About the methods we conclude that the statistic for aggregation provides insight into clustering of life span and the statistic for linkage provides a new tool to include demographic information into the analysis.