Table S1 is a list of 281 SNPs included in the genetic risk model. This is an excel file with 3 worksheets: README worksheet describes the column contents; 281 SNPs worksheet describes the list of 281 SNPs used in the ensemble genetic risk models including details about call rate by array type and phenotype, details of QC, statistical analysis. Functional annotation worksheet includes functional annotation of the 281 SNPs.

Figure S19 reports on the posterior probability of exceptional and average longevity for different genotypes of rs2075650. The ROC analysis shows that this SNP alone cannot optimize the trade-off between sensitivity and specificity. The area under the curve is 0.62 compared to 0.95 when 281 SNPs are used in the model (Figure S7, top, left panel). Note that some threshold on the posterior probability can produce an accuracy that is worse than random classification.

Table S3 lists the rate of disease-associated variants carried by centenarians and controls, and p-value from Students T test. Risk alleles were derived from the GWAS catalogue at the NHGRI (downloaded in April 2011) and the Human Genome Mutation Database. The boxplots display the rate of risk alleles carried by centenarians (blue) and controls (red). The diseases described are: lupus, cholesterol level (Chol), macular degeneration (MD), Parkinson's Disease (PD), Chrons disease (chr), diabetes (diab), cardiovascular disease (CVD), cancer (canc)r, Alzheimer's (AD), GWAS.pt is the group of alleles related to personality disorders that were found in GWAS, gwas.qt is the group of alleles related to QTL from GWASs and includes cholesterol, BMI, obesity, etc., and GWAS.cc is the group of risk alleles found from case/control GWASs so includes for example cancer, PD, MD etc., cod is for coding variants from the HGMD, and all is the full set of 1214 variants.

Table S4 lists disease-associated SNPs that showed significant differences in the discovery sets. Highlighted in grey are the SNPs with risk alleles that are less common in centenarians. Some SNPs had unreported risk alleles in the original publications denoted with a question mark.

The two pedigrees show examples of familial longevity although the genetic risk profiles of the two centenarian probands (red arrows) show no enrichment of longevity-associated variants. This could indicate that such families have more private or rare variants not captured by either the genotyping or the model. Figure S21 shows the agreement of allele frequencies in different centenarians genotyped with array HumanHap370 (x-axis) and 168 centenarians genotyped with the HumanHap 1 M (y-axis). Panel B shows the allele frequency in 151 controls typed with array HumanHap330 (x-axis) and 863 with HumanHap 550 (y-axis). Panel C shows the allele frequency in 241 controls typed with array HumanHap370 (x-axis) and 863 with Human- Hap 550 (y-axis).

The study was conceived and designed by PS CB MS MM JH TP. The experiments were performed by CB EM AD KW JH. The data was analyzed by PS NS SH DD AD KW JH. AP JW RM SA contributed reagents/materials/analysis tools. The paper was written by PS NS MS MM JH TP.