Because we recently obtained Illumina Human660W-Quad and Human- OmniExpress GWAS data for participants in the LLS, we were able to in- vestigate potential substructure. First, in PLINK version 1.07 (http://pngu. mgh.harvard.edu/purcell/plink/) (27) for 10,000 random SNPs, IBS (identity- by-state) estimates for all pairs of subjects in the samples were computed. Next, we performed a multidimensional scaling (mds) analysis on the N × N matrix of genome-wide IBS pairwise distances, using the mds-plot option in conjunction with clustering. The C1 values were plotted against C2 values to identify clustering among the subjects and controls (Fig. S2). We conclude that there is no substructure among the participants of the LLS to an extent that would affect our conclusions.

ACKNOWLEDGMENTS. We thank all participants of the Leiden Longevity Study, Leiden 85 Plus Study, and Netherlands Twin Register. This study was supported by a grant from the Innovation Oriented Research Program on Genomics (SenterNovem IGE05007), the Centre for Medical Systems Biology, and the National Institute for Healthy Ageing (Grant 05060810), all in the framework of the Netherlands Genomics Initiative/Netherlands Organiza- tion for Scientific Research. The data collection of the Netherlands Twin Register is supported by the Netherlands Organization for Scientific Re- search (Grants NWO904-61-090, NWO904-61-193, NWO480-04-004, and NWO400-05-717), Center for Medical Systems Biology (NWO Genomics), and Spinozapremie (Grant NWO-SPI 56-464-14192).

Leiden 85 Plus Study. In the Leiden 85 Plus Study, two prospective population- based cohorts consisting of inhabitants of Leiden aged 85 y and older were followed.Between1987and1989(cohort1),673subjectsaged85yandolder of Dutch ancestry and white ethnicity were enrolled and followed up for survival for 17 y; during this time, 672 subjects (99.9%) died. Between 1997 and 1999, 563 subjects were enrolled in the month of their 85th birthday (cohort 2) and followed up for survival for 10 y; during this time, 453 subjects (81%) died. Subjects were visited at their home, and there were no exclusion

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