Discovery and Replication Case:Control Sample Sets.

<p>Contributing project totals in discovery and replication phases. The totals represent the number of high quality datasets derived from samples.</p

Manhattan Plot of SNP based CNV Statistics. (A)Deletions and (B)Duplications.

<p>Manhattan Plot of SNP based CNV Statistics. (A)Deletions and (B)Duplications.</p

Representative Interactions of the Lifespan Longevity Associated Genes Identified.

<p>Gene-gene interactions of independently significant loci. Additional genes implicated by interacting with genes in significantly associated longevity loci. Alternative splicing gene function annotation enrichment of significant loci suggests diverse genetic perturbation with a common biological role. Extension of this functional category to other genes annotated by functional studies with interactions to associated genes implicates potential for screening diverse etiology.</p

Principle Components Analysis of Pediatric and Geriatric Cohorts.

<p>Discovery U.S. Pediatric vs. Icelandic Geriatric A) Principle components (PC) 1 vs. 2 shows distinct clusters likely due to sporadic differential profiles of a specific subset of SNPs between arrays. Since CNV calling is based on multiple neighboring SNPs and differential clustering SNPs are randomly distributed, CNV discovery should not experience significant bias. B) PC2 vs. 3 representing population structure showing some overlap of pediatric and geriatric cohorts C) SNP genotype allele frequency differences genome wide showing close correlation. Replication U.S. Pediatric vs. U.S. Geriatric D) Replication of U.S. pediatric and U.S. geriatric PC1 vs. PC2 showing high overlap unlike panel A U.S. pediatric and Icelandic geriatric E) Geriatric replication cohort in isolation for clarity F) Population structure of pediatric subjects with significantly associated risk CNVs for short lifespan showing broad normal distribution minimizing test statistic inflation for rare variants opposed to tight clustering(37) G) Pediatric replication cohort in isolation for clarity.</p

CNVs Enriched in Pediatric Individuals.

*<p>Gene not overlapped so closest proximal gene annotated. Gene delimiters were defined based on UCSC genes table reference including exons and introns. Any direct overlap of any segment of the gene delimiters is considered a hit such that complete overlap of the gene is not required. Combined p-values were calculated using Fisher’s method.</p

CNVs Enriched in Geriatric Individuals.

<p>CNVs Enriched in Geriatric Individuals.</p

Independent Technology Validation of Presence of CNV Events to Confirm CNVs Detected by Illumina Array.

<p>Error bars denote the standard deviation of quadruplicate runs.</p