from application) This project involves the collection, extraction, storage and analysis of DNA samples from approximately 800 living complete twin-pairs who are members of the National Academy of Sciences-National Research Council World War II twin registry. Twins will be selected from complete pairs who responded to a recent epidemiologic mail questionnaire between September 1998 and December 1999 when the participants were at a mean age of 74. Twin-pairs recruited will be those where one or both co-twins indicated they did not have (or ever had) any cardiovascular disease (heart attack, coronary surgery, stroke, or hypertension), diabetes mellitus, or prostate cancer. Such individuals are hypothesized to have a better complement of genes related to good health and aging, and a greater probability of longevity. Genome wide scanning of DNA markers will be undertaken for fraternal (DZ) twins concordant for freedom from the above diseases using sib-pair methods. Regions suggestive of linkage will be further analyzed and fine mapping performed using DZ pairs discordant for the trait as defined above. The discordant DZ pairs serve as a complement to the analysis of concordant pairs and provide an independent confirmatory sample. A group of identical (MZ) twins will also be collected for co-twin-control studies of potential environmental influences. The DNA collected will serve as a repository for future studies on diseases related to aging and longevity, and for confirmation of linkages suggested by other sources. The DNA samples will also be a resource for follow-up genetic epidemiologic studies on the twins' middle aged offspring. For genes of interest, the rate of change in physiologic measures associated with aging can be compared between siblings who did and did not receive the same set of genes from their twin dads.
