Materials and Methods

StudyPopulation.Atotalsampleof1,031unrelatedGermanLLIwasstudiedthat were recruited from different geographic regions throughout Germany. Nona- genariansandcentenarianswerebetween95and110yearsofageatthetimeof recruitment (mean age: 98.4 years). The gender ratio was 74.1% females vs. 25.9%males.Asubsetcomprised388centenarians(meanage:101.6years).The 731Germanyoungercontrolsubjectswerebetween60and75yearsofage(mean age:67.2years).Therearenomortalitydataavailableforthecontrols.However, basedoncurrentpredictionsonly1.5%ofall60-year-oldand1.8%ofall75-year- old German females will become 100 years. For males, the probability is even lower (Human Mortality Database; www.demogr.mpg.de). Hence, we can esti- mate that only (cid:4)13 of our younger controls (of 731) will become centenarians themselves, a negligible proportion that does not affect power. In Germany geneticdifferentiationinpopulationstructureisconsideredtobeverylow(20). Moreover, the recruited controls match the LLI as closely as possible in terms of ancestry,gender,andgeographicaloriginwithinthecountry(13),thusminimiz- ing any systematic genetic differences between the samples that might arise becauseofverylowlevelsofundetectedpopulationstructure.Thegoodmatch- ing is reflected in a genomic inflation factor (cid:2)of 1.02 (centenarian group) and 1.00 (LLI sample), respectively, using PLINK version 1.01 (21) (http://pngu.mgh.

PowercalculationswereperformedbyusingthePSPowerandSampleSize Program (26) (http://medipe.psu.ac.th/episoft/pssamplesize). Single-marker association analyses with adjustment for gender and APOE, and OR statistics were conducted by logistic regression in R, version 5.2.1 (ref. 27 and www.R- project.org).

ACKNOWLEDGMENTS. We thank all study participants for their coopera- tion and the laboratory personnel of the Institute of Clinical Molecular Biology, the members of the Popgen Biobank, and the staff of the Biolog- ical Resource Center of the Fondation Jean Dausset–Centre d’E´tude du Polymorphisme Humain for excellent technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft Excellence Cluster Inflammation at Interfaces, the German Federal Ministry of Science and Education through an Explorative Project of the National Genome Re- search Network, the French Ministe`re de l’Enseignement Supe´rieur et de la Recherche, and the Genetics of Healthy Aging Consortium, 6. Framework Program of the European Commission.

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