This is a revised application for the development of a genetic resource in the English Longitudinal Study of Ageing (ELSA). This grant will focus on genes (APOE and the glucocorticoid receptor gene) that will provide information on the hypothesized pathways between social position and health. We will focus on three outcomes that vary with social position such that there is increased risk in lower social groups; cardiovascular status (using metabolic syndrome score), cognitive performance and physical performance. ELSA is a cohort study of health, social and economic issues and their inter-relationships in aging, funded by the National Institute on Aging and the British Government. Although modeled on the Health and Retirement Study, ELSA is uniquely suited for genetic studies because alongside a wealth of social, psychosocial, economic and health data it crucially includes biological and performance data not available in comparative US studies. Current funding provides support until September 2005, including for collection of blood samples in 2004. This application seeks a study enhancement to create a DNA repository. The richness of the psychosocial and economic data, together with well characterized phenotypes will create a world class program exploring the contribution of candidate polymorphisms to the pathways involved in accelerated aging or increased levels of age related impairments in lower social groups. An initial program of examining 8 polymorphisms on the APOE gene will provide an estimate of the effect of well-studied polymorphisms on endophenotypes and definitive estimates of the importance of the less studied and new markers. Additionally, we plan to examine 6 polymorphisms in the glucocorticoid receptor gene, which is part of the hypothalamic-pituitary-adrenal axis. Examination of these genes will allow us to explore pathways important in social determinants of health and investigate the contribution of candidate genes. The repository will serve as the basis for the specified research questions and will provide genetic information for other studies concentrating on other research questions. ? ?
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