The underlying genetic factors that influence determinants of urinary SS, such as calcium excretion, are poorly defined. This project addresses these gaps in knowledge by identifying genetic associations with urinary lithogenic factors. To do so we have assembles a multidisciplinary team including epidemiologists, geneticists, basic scientists and clinicians. A key and unique resource for our proposal is the Rochester, MN cohort of the Genetic Epidemiology Network of Arteriopathy (GENOA), which has conducted genome-wide linkage and association studies to identify genes influencing blood pressure, and the cerebral, cardiac, and peripheral vascular complications of HTN. Members of the well-characterized GENOA cohort are being phenotyped for kidney stone risk via 24-hr urine collections in which measure lithogenic factors including calcium, oxalate, citrate, and uric acid excretion, as well as overall crystallization inhibition. Modifiers such as diet intake will also be carefully quantified using appropriate urinary biomarker indices of key diet components (sodium, potassium, protein, net gastrointestinal alkali absorption), supplemented by detailed food frequency questionnaires and diet diaries to compare diet components best assessed by these methods (calcium, oxalate). Extensive pre-existing SNP data available for the GENOA cohort will be used to analyze 11 candidate genes as well as to perform genome-wide association studies to define genetic determinants of urinary lithogenicity. Together, these studies will determine if polymorphic variation at specific geneomic loci or in previously implicated NL candidate genes influence urinary lithogenic factors (e.g., 24 hr-hr excretion of calcium, oxalate, citrate, or uric acid; ULM). In this supplement we request funds for increased study coordinator time (additional 0.75 FTE). This will increase our capacity to rapidly recruit patients for their study visits. With additional support, we will be able to roughly double our pace of recruiting, and thereby slightly increase our recruitment target to 1200 subjects yet still allow at least one full year for analyses before a renewal application is due. This accelerated timeframe will also allow time within the current funding period for additional genotyping of SNPs and candidate genes as indicated by initial analyses.