clusters with 8 or more centenarians are included. Several of the signatures discovered in the replication set match signatures in the discovery set: The pattern of R1 matches C1, R2 matches C2, R4

Table S1 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. This includes details about call rate by array type and phenotype, details of QC, statistical analysis. ‘‘Functional annotation’’ worksheet includes functional annotation of the 281 SNPs. (XLS)

age of events, and the y-axis reports the event-free survival distribution. Only subjects with events were included in the analysis. The caption below each plot indicates the disease and the p-value to test significance differences using the log-rank test. Median ages of onsets are in the insets. Subjects in cluster C1 had a significant delay in the onset of dementia and stroke, compared to other clusters. They also delayed onset of cancer compared to centenarians with signatures C2, C3 and C5, but not differently from centenarians with signature C6, and delayed cardiovascular disease compared to centenarians with other signatures but not differently from centenarians with signature C3. Ages of onset of other diseases also differ between other clusters. (TIF)

defined as angina, congestive heart failure, peripheral circulatory disease or myocardial infarction; pulmonary disease is asthma, chronic bronchitis or emphysema; hypertension: systolic blood pressure .140 mm Hg and/or diastolic blood pressure .90 mm Hg or on medication for HTN. (DOCX)

Table S3 Rate of disease associated variants carried by centenarians and controls, and p-value from Student’s T

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. (TIF)

test. Risk alleles were derived from the GWAS catalogue at the NHGRI (downloaded in April 2011) and the Human Genome Mutation Database. The boxplots displays the rate of risk alleles carried by centenarians (blue) and controls (red). The disease described are: lupus, cholesterol level (Chol), macular degenera- tion (MD), Parkinson’s Disease (PD), Chron’s disease (chr), diabetes (diab), cardiovascular disease (CVD), cance (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 include cholesterol, BMI, obesity etc, and GWAS.cc is the group of risk alleles found from case/control GWASs so include for example cancer, PD, MD etc, cod is for coding variants from the HGMD, and all is the full set of 1214 variants. (DOCX)

Figure S19 Predictive value of the SNP rs2075650 in TOMM40/APOE in the discovery set. The table reports 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 S4 List of 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 that are denoted with a question mark.

Acknowledgments

Figure S21 Agreement of allele frequencies in different

We thank the subjects and family members participating in the New England Centenarian Study and the Elixir Pharmaceuticals Centenarian Study.

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 C) shows the allele frequency in 241 controls typed with array HumanHap370 (x-axis) and 863 with Human- Hap 550 (y-axis). (TIF)

Author Contributions

Conceived and designed the experiments: PS CB MS MM JH TP. Performed the experiments: CB EM AD KW JH. Analyzed the data: PS NS SH DD AD KW JH. Contributed reagents/materials/analysis tools: AP JW RM SA. Wrote the paper: PS NS MS MM JH TP.

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