The genotype data of the 31 SNPs in the genes ADARB1 and 114 SNPs in ADARB2 were individually analyzed using Bayesian logistic regression [32] to fit dominant and recessive models of inheritance adjusted by gender. The marginal posterior distributions of the ORs were estimated using the implementation of Gibbs sampling in WinBugs 1.4 [50]. The 2.5th and 97.5th percentile were used to estimate 95% credible intervals (CI) for the ORs. The Gibbs sampler was run for at least 10,000 iterations and the last 10,000 simulated values were used to estimate these parameters.

18 significant SNPs were identified (Table 3), which is more than twice the number expected by chance in 145 independent tests, and two SNPs remained significant even after correcting for the threshold for the number of tests. An association that was significant in the aggregated NECS and SICS data was deemed replicated in either the AJCS or JCS studies if the same SNP was significant (Bayes significance, 0.05) with the same genetic model and consistent effects. The results are in Tables 4, 5, 6, and 7.

We conducted a similar analysis stratified by gender, but the limited sample sizes did not produce strongly significant results.

HaploView 4.1 was used to create the LD heatmaps, and LD displays were generated using the D9 color scheme where white represents D9=0, red represents D9=1, and different shades of red represent 0<D9<1 (Figures 1 and 4).

To synchronize worms for lifespan measurements in C. elegans, eggs were isolated (N2, adr-1, adr-2, adr-1;adr-2, rde-1, rde-4, adr-1;adr-2;rde-1) and synchronized by hatching overnight in the absence of food at 20C. Synchronized L1 larvae were counted and platedcomponents in controls of the SICS, which also display a SW European genetic background. The principal component analysis suggests that the NECS and SICS centenarians are genetically distinct from each other and from the Illumina controls, while sharing genetic ancestry with their respective controls. The population substructure observed in the controls should be taken into account in association studies of exceptional longevity in these cohorts. doi:10.1371/journal.pone.0008210.g005The text appears to be a mix of different sections, and it is unclear what the overall context is. As such, it is difficult to make meaningful corrections without additional information. Please provide more context or specify which section(s) require proofreading and improvement.Al. (2013) Genes, aging, and longevity in humans: problems, advantages, and perspectives. Free Radic Res 47(10): 749-64.

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