Genetic and environmental factors play an important role in the etiology of nephrolithiasis. This project will build on and extend our previous efforts (examining environmental risk factors for stone formation) by allowing us to study the risk of stone formation associated with specific genes and gene-environment interactions. We will take advantage of previously collected data in three large cohort studies: Nurses' Health Study I (n=121,000 women), Nurses'Health Study II (n=116,000 women), and Health Professionals Follow-up Study (n=51,000 men). Over a period of 14 to 24 years, information has been collected prospectively on important exposures including diet, family history, body size measures, past medical history, and medications. We have confirmed over 1600 incident cases of kidney stones in each cohort and are in the process of identifying additional incident cases (DK59583, PI Curhan). Further, we have collected 24-hour urine samples from over 3000 cases and controls and will collect another ~1000 over the next three years;the majority of participants have performed two collections. Using a nested case-control design, the primary objective of this project is to examine the role of specific genetic risk factors for incident nephrolithiasis. The secondary objective is to explore interactions between the genetic factors, dietary factors (particularly calcium intake) and risk of incident stone formation. The final objective is to examine the impact of these genetic factors and gene-environment interactions on 24-hour urinary excretion of relevant lithogenic factors. This project will interact with each of the other projects and cores. Polymorphisms and haplotypes from Projects 1-3, as well as additional gene candidates identified from the Genetics Core, will greatly enhance the scope and depth of this study, and will increase the likelihood of identifying clinically meaningful associations between genetic factors/diet, the urinary supersaturation of calcium salts/and kidney stone formation. A P-value of 0.001 will be used as the threshold for statistical significance to reduce the likelihood of false-positive associations. These findings should provide insight into new approaches for prevention of stone formation.
| Mandal, Asim K; Mercado, Adriana; Foster, Andria et al. (2017) Uricosuric targets of tranilast. Pharmacol Res Perspect 5:e00291 |
| Pirastu, Nicola; Joshi, Peter K; de Vries, Paul S et al. (2017) GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk. Nat Commun 8:1584 |
| Canales, Benjamin K; Smith, Jennifer A; Weiner, I David et al. (2017) Polymorphisms in Renal Ammonia Metabolism Genes Correlate With 24-Hour Urine pH. Kidney Int Rep 2:1111-1121 |
| Ibrahim-Verbaas, C A; Bressler, J; Debette, S et al. (2016) GWAS for executive function and processing speed suggests involvement of the CADM2 gene. Mol Psychiatry 21:189-197 |
| Cornelis, Marilyn C; Flint, Alan; Field, Alison E et al. (2016) A genome-wide investigation of food addiction. Obesity (Silver Spring) 24:1336-41 |
| Huang, Tao; Qi, Qibin; Zheng, Yan et al. (2015) Genetic Predisposition to Central Obesity and Risk of Type 2 Diabetes: Two Independent Cohort Studies. Diabetes Care 38:1306-11 |
| Zimmermann, E; Ängquist, L H; Mirza, S S et al. (2015) Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults. Obes Rev 16:327-340 |
| Gottlieb, D J; Hek, K; Chen, T-H et al. (2015) Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study. Mol Psychiatry 20:1232-9 |
| Ferraro, Pietro Manuel; Curhan, Gary C; Sorensen, Mathew D et al. (2015) Physical activity, energy intake and the risk of incident kidney stones. J Urol 193:864-8 |
| Taylor, Eric N; Hoofnagle, Andrew N; Curhan, Gary C (2015) Calcium and phosphorus regulatory hormones and risk of incident symptomatic kidney stones. Clin J Am Soc Nephrol 10:667-75 |
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