replication of the initial observations from the Danish case-control study, two German samples of 1,613 unrelated long-lived individuals (age 95-110) and 1,140 middle-aged controls (mean age 67.2) were used. The participants were identified through local registry offices and from the Federal Administrative Office. They were recruited from the different geographic regions of Germany and were all of German ancestry (Nebel et al. 2005). Approval was received from the Ethics Committee of the University Hospital Schleswig-Holstein. For replication of initial findings from theThe SNPs were analyzed, and the P-set value was corrected for multiple testing based on the number of SNPs in each gene. In the replication study, genotype data from the Leiden 85-plus Study were used to perform survival analysis using a sex-adjusted Cox proportional hazard model in Stata 11.1. Kaplan Meier plots were generated for the Dutch and Danish cohorts in Stata 11.1. For all analyses, a nominal significance level of 0.05 was set, and correction for multiple testing was performed using the permutation approach with max(T) permutation mode set at 10,000 permutations for analyses carried out in Plink and R software. LD estimates for APOE SNPs were obtained using Plink software, and the LD data were used in HaploView software (http://www.broadinstitute.org/haploview/haploview; Barrett et al. 2005) to generate an APOE LD plot. The expression measurements of IL6 data were analyzed using linear regression of C and rs2069827 genotype data in STATA 11.1 statistical program, adjusting for age at blood sampling (the latter was initially observed to be a confounder). The assumptions of normal distribution and equal variance were tested for Ct by Shapiro Wilk and Breusch Pagan/Cook Weisberg tests. A box plot of mean Ct by rs2069827 genotype groups was generated in STATA 11.1. In the Danish longitudinal study, two survival variables were applied to explore the genetic contribution to surviving for a short period versus a longer period during the ninth decade of life. The distribution of survival times was right-skewed (data not shown); hence, a cutoff with respect to survival data on the oldest-old Danes was performed.