The efficiency of genetic analysis of DNA from aged siblings to detect chromosomal regions implicated in longevity

Studies of the frequencies of different alleles in young adults and aged in dividuals have implicated several genes, such as ApoE and ACE, in longevity . However such association studies can easily give rise to spurious results through unsuspected population subdivision, and an approach making use of genetic relationships among relatives is desirable. We have studied the eff ectiveness of non-parametric genetic analysis to detect different types of loci affecting longevity. The non-parametric method has high statistical po wer to detect infrequent recessive alleles that are required for, or signif icantly increase the probability of, survival to advanced age. Statistical power is reduced if a proportion of carriers of the alternative allele is a llowed to survive. The method is least effective in detecting alleles that occur at low frequency in young individuals and that subsequently experienc e high mortality, as is the case for carriers of the epsilon 4 allele of Ap oE. Genotyping errors will also reduce the value of the NPL statistic in a linear fashion with the error rate and the number of loci genotyped. We hav e also used the method to analyse genotypes of seven highly polymorphic mar kers near the ApoE gene in a sample of 188 sibships of nonagenarians and ce ntenarians (n = 434) and their children (n = 124), however no excess sharin g of alleles was detected. (C) 2000 Elsevier Science Ireland Ltd. All right s reserved.