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1. Genome-wide meta-analysis of variant-by-diuretic interactions as modulators of lipid traits in persons of European and African ancestry

Author

de las Fuentes, L., Sung, Y. J., Sitlani, C. M., Avery, C. L., Bartz, T. M., Keyser, C. de, Evans, D. S., Li, X., Musani, S. K., Ruiter, R., Smith, A. V., Sun, F., Trompet, S., Xu, H., Arnett, D. K., Bis, J. C., Broeckel, U., Busch, E. L., Chen, Y.-D. I., Correa, A., Cummings, S. R., Floyd, J. S., Ford, I., Guo, X., Harris, T. B., Ikram, M. A., Lange, L., Launer, L. J., Reiner, A. P., Schwander, K., Smith, N. L., Sotoodehnia, N., Stewart, J. D., Stott, D. J., Stürmer, T., Taylor, K. D., Uitterlinden, A., Vasan, R. S., Wiggins, K. L., Cupples, L. A., Gudnason, V., Heckbert, S. R., Jukema, J. W., Liu, Y., Psaty, B. M., Rao, D. C., Rotter, J. I., Stricker, B., Wilson, J. G., and Whitsel, E. A.

Published
2020
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2. Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group

Author

Floyd, J S, Sitlani, C M, Avery, C L, Noordam, R, Li, X, Smith, A V, Gogarten, S M, Li, J, Broer, L, Evans, D S, Trompet, S, Brody, J A, Stewart, J D, Eicher, J D, Seyerle, A A, Roach, J, Lange, L A, Lin, H J, Kors, J A, Harris, T B, Li-Gao, R, Sattar, N, Cummings, S R, Wiggins, K L, Napier, M D, Stürmer, T, Bis, J C, Kerr, K F, Uitterlinden, A G, Taylor, K D, Stott, D J, de Mutsert, R, Launer, L J, Busch, E L, Méndez-Giráldez, R, Sotoodehnia, N, Soliman, E Z, Li, Y, Duan, Q, Rosendaal, F R, Slagboom, P E, Wilhelmsen, K C, Reiner, A P, Chen, Y-DI, Heckbert, S R, Kaplan, R C, Rice, K M, Jukema, J W, Johnson, A D, Liu, Y, Mook-Kanamori, D O, Gudnason, V, Wilson, J G, Rotter, J I, Laurie, C C, Psaty, B M, Whitsel, E A, Cupples, L A, and Stricker, B H

Published
2018
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4. Meta-analyses identify DNA methylation associated with kidney function and damage

Author

Schlosser, P. (Pascal), Tin, A. (Adrienne), Matias-Garcia, P. R. (Pamela R.), Thio, C. H. (Chris H. L.), Joehanes, R. (Roby), Liu, H. (Hongbo), Weihs, A. (Antoine), Yu, Z. (Zhi), Hoppmann, A. (Anselm), Grundner-Culemann, F. (Franziska), Min, J. L. (Josine L.), Adeyemo, A. A. (Adebowale A.), Agyemang, C. (Charles), Arnlov, J. (Johan), Aziz, N. A. (Nasir A.), Baccarelli, A. (Andrea), Bochud, M. (Murielle), Brenner, H. (Hermann), Breteler, M. M. (Monique M. B.), Carmeli, C. (Cristian), Chaker, L. (Layal), Chambers, J. C. (John C.), Cole, S. A. (Shelley A.), Coresh, J. (Josef), Corre, T. (Tanguy), Correa, A. (Adolfo), Cox, S. R. (Simon R.), de Klein, N. (Niek), Delgado, G. E. (Graciela E.), Domingo-Relloso, A. (Arce), Eckardt, K.-U. (Kai-Uwe), Ekici, A. B. (Arif B.), Endlich, K. (Karlhans), Evans, K. L. (Kathryn L.), Floyd, J. S. (James S.), Fornage, M. (Myriam), Franke, L. (Lude), Fraszczyk, E. (Eliza), Gao, X. (Xu), Gao, X. (Xin), Ghanbari, M. (Mohsen), Ghasemi, S. (Sahar), Gieger, C. (Christian), Greenland, P. (Philip), Grove, M. L. (Megan L.), Harris, S. E. (Sarah E.), Hemani, G. (Gibran), Henneman, P. (Peter), Herder, C. (Christian), Horvath, S. (Steve), Hou, L. (Lifang), Hurme, M. A. (Mikko A.), Hwang, S.-J. (Shih-Jen), Järvelin, M.-R. (Marjo-Riitta), Kardia, S. L. (Sharon L. R.), Kasela, S. (Silva), Kleber, M. E. (Marcus E.), Koenig, W. (Wolfgang), Kooner, J. S. (Jaspal S.), Kramer, H. (Holly), Kronenberg, F. (Florian), Kuhnel, B. (Brigitte), Lehtimaki, T. (Terho), Lind, L. (Lars), Liu, D. (Dan), Liu, Y. (Yongmei), Lloyd-Jones, D. M. (Donald M.), Lohman, K. (Kurt), Lorkowski, S. (Stefan), Lu, A. T. (Ake T.), Marioni, R. E. (Riccardo E.), Marz, W. (Winfried), McCartney, D. L. (Daniel L.), Meeks, K. A. (Karlijn A. C.), Milani, L. (Lili), Mishra, P. P. (Pashupati P.), Nauck, M. (Matthias), Navas-Acien, A. (Ana), Nowak, C. (Christoph), Peters, A. (Annette), Prokisch, H. (Holger), Psaty, B. M. (Bruce M.), Raitakari, O. T. (Olli T.), Ratliff, S. M. (Scott M.), Reiner, A. P. (Alex P.), Rosas, S. E. (Sylvia E.), Schottker, B. (Ben), Schwartz, J. (Joel), Sedaghat, S. (Sanaz), Smith, J. A. (Jennifer A.), Sotoodehnia, N. (Nona), Stocker, H. R. (Hannah R.), Stringhini, S. (Silvia), Sundstrom, J. (Johan), Swenson, B. R. (Brenton R.), Tellez-Plaza, M. (Maria), van Meurs, J. B. (Joyce B. J.), van Vliet-Ostaptchouk, J. V. (Jana V.), Venema, A. (Andrea), Verweij, N. (Niek), Walker, R. M. (Rosie M.), Wielscher, M. (Matthias), Winkelmann, J. (Juliane), Wolffenbuttel, B. H. (Bruce H. R.), Zhao, W. (Wei), Zheng, Y. (Yinan), Loh, M. (Marie), Snieder, H. (Harold), Levy, D. (Daniel), Waldenberger, M. (Melanie), Susztak, K. (Katalin), Kottgen, A. (Anna), Teumer, A. (Alexander), Schlosser, P. (Pascal), Tin, A. (Adrienne), Matias-Garcia, P. R. (Pamela R.), Thio, C. H. (Chris H. L.), Joehanes, R. (Roby), Liu, H. (Hongbo), Weihs, A. (Antoine), Yu, Z. (Zhi), Hoppmann, A. (Anselm), Grundner-Culemann, F. (Franziska), Min, J. L. (Josine L.), Adeyemo, A. A. (Adebowale A.), Agyemang, C. (Charles), Arnlov, J. (Johan), Aziz, N. A. (Nasir A.), Baccarelli, A. (Andrea), Bochud, M. (Murielle), Brenner, H. (Hermann), Breteler, M. M. (Monique M. B.), Carmeli, C. (Cristian), Chaker, L. (Layal), Chambers, J. C. (John C.), Cole, S. A. (Shelley A.), Coresh, J. (Josef), Corre, T. (Tanguy), Correa, A. (Adolfo), Cox, S. R. (Simon R.), de Klein, N. (Niek), Delgado, G. E. (Graciela E.), Domingo-Relloso, A. (Arce), Eckardt, K.-U. (Kai-Uwe), Ekici, A. B. (Arif B.), Endlich, K. (Karlhans), Evans, K. L. (Kathryn L.), Floyd, J. S. (James S.), Fornage, M. (Myriam), Franke, L. (Lude), Fraszczyk, E. (Eliza), Gao, X. (Xu), Gao, X. (Xin), Ghanbari, M. (Mohsen), Ghasemi, S. (Sahar), Gieger, C. (Christian), Greenland, P. (Philip), Grove, M. L. (Megan L.), Harris, S. E. (Sarah E.), Hemani, G. (Gibran), Henneman, P. (Peter), Herder, C. (Christian), Horvath, S. (Steve), Hou, L. (Lifang), Hurme, M. A. (Mikko A.), Hwang, S.-J. (Shih-Jen), Järvelin, M.-R. (Marjo-Riitta), Kardia, S. L. (Sharon L. R.), Kasela, S. (Silva), Kleber, M. E. (Marcus E.), Koenig, W. (Wolfgang), Kooner, J. S. (Jaspal S.), Kramer, H. (Holly), Kronenberg, F. (Florian), Kuhnel, B. (Brigitte), Lehtimaki, T. (Terho), Lind, L. (Lars), Liu, D. (Dan), Liu, Y. (Yongmei), Lloyd-Jones, D. M. (Donald M.), Lohman, K. (Kurt), Lorkowski, S. (Stefan), Lu, A. T. (Ake T.), Marioni, R. E. (Riccardo E.), Marz, W. (Winfried), McCartney, D. L. (Daniel L.), Meeks, K. A. (Karlijn A. C.), Milani, L. (Lili), Mishra, P. P. (Pashupati P.), Nauck, M. (Matthias), Navas-Acien, A. (Ana), Nowak, C. (Christoph), Peters, A. (Annette), Prokisch, H. (Holger), Psaty, B. M. (Bruce M.), Raitakari, O. T. (Olli T.), Ratliff, S. M. (Scott M.), Reiner, A. P. (Alex P.), Rosas, S. E. (Sylvia E.), Schottker, B. (Ben), Schwartz, J. (Joel), Sedaghat, S. (Sanaz), Smith, J. A. (Jennifer A.), Sotoodehnia, N. (Nona), Stocker, H. R. (Hannah R.), Stringhini, S. (Silvia), Sundstrom, J. (Johan), Swenson, B. R. (Brenton R.), Tellez-Plaza, M. (Maria), van Meurs, J. B. (Joyce B. J.), van Vliet-Ostaptchouk, J. V. (Jana V.), Venema, A. (Andrea), Verweij, N. (Niek), Walker, R. M. (Rosie M.), Wielscher, M. (Matthias), Winkelmann, J. (Juliane), Wolffenbuttel, B. H. (Bruce H. R.), Zhao, W. (Wei), Zheng, Y. (Yinan), Loh, M. (Marie), Snieder, H. (Harold), Levy, D. (Daniel), Waldenberger, M. (Melanie), Susztak, K. (Katalin), Kottgen, A. (Anna), and Teumer, A. (Alexander)

Abstract

Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.

Published
2021

5. Genome-wide meta-analysis of variant-by-diuretic interactions as modulators of lipid traits in persons of European and African ancestry

Author

de las Fuentes, L., primary, Sung, Y. J., additional, Sitlani, C. M., additional, Avery, C. L., additional, Bartz, T. M., additional, Keyser, C. de, additional, Evans, D. S., additional, Li, X., additional, Musani, S. K., additional, Ruiter, R., additional, Smith, A. V., additional, Sun, F., additional, Trompet, S., additional, Xu, H., additional, Arnett, D. K., additional, Bis, J. C., additional, Broeckel, U., additional, Busch, E. L., additional, Chen, Y.-D. I., additional, Correa, A., additional, Cummings, S. R., additional, Floyd, J. S., additional, Ford, I., additional, Guo, X., additional, Harris, T. B., additional, Ikram, M. A., additional, Lange, L., additional, Launer, L. J., additional, Reiner, A. P., additional, Schwander, K., additional, Smith, N. L., additional, Sotoodehnia, N., additional, Stewart, J. D., additional, Stott, D. J., additional, Stürmer, T., additional, Taylor, K. D., additional, Uitterlinden, A., additional, Vasan, R. S., additional, Wiggins, K. L., additional, Cupples, L. A., additional, Gudnason, V., additional, Heckbert, S. R., additional, Jukema, J. W., additional, Liu, Y., additional, Psaty, B. M., additional, Rao, D. C., additional, Rotter, J. I., additional, Stricker, B., additional, Wilson, J. G., additional, and Whitsel, E. A., additional

Published
2019
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6. Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology

Author

Seyerle, A A, primary, Sitlani, C M, additional, Noordam, R, additional, Gogarten, S M, additional, Li, J, additional, Li, X, additional, Evans, D S, additional, Sun, F, additional, Laaksonen, M A, additional, Isaacs, A, additional, Kristiansson, K, additional, Highland, H M, additional, Stewart, J D, additional, Harris, T B, additional, Trompet, S, additional, Bis, J C, additional, Peloso, G M, additional, Brody, J A, additional, Broer, L, additional, Busch, E L, additional, Duan, Q, additional, Stilp, A M, additional, O'Donnell, C J, additional, Macfarlane, P W, additional, Floyd, J S, additional, Kors, J A, additional, Lin, H J, additional, Li-Gao, R, additional, Sofer, T, additional, Méndez-Giráldez, R, additional, Cummings, S R, additional, Heckbert, S R, additional, Hofman, A, additional, Ford, I, additional, Li, Y, additional, Launer, L J, additional, Porthan, K, additional, Newton-Cheh, C, additional, Napier, M D, additional, Kerr, K F, additional, Reiner, A P, additional, Rice, K M, additional, Roach, J, additional, Buckley, B M, additional, Soliman, E Z, additional, de Mutsert, R, additional, Sotoodehnia, N, additional, Uitterlinden, A G, additional, North, K E, additional, Lee, C R, additional, Gudnason, V, additional, Stürmer, T, additional, Rosendaal, F R, additional, Taylor, K D, additional, Wiggins, K L, additional, Wilson, J G, additional, Chen, Y-DI, additional, Kaplan, R C, additional, Wilhelmsen, K, additional, Cupples, L A, additional, Salomaa, V, additional, van Duijn, C, additional, Jukema, J W, additional, Liu, Y, additional, Mook-Kanamori, D O, additional, Lange, L A, additional, Vasan, R S, additional, Smith, A V, additional, Stricker, B H, additional, Laurie, C C, additional, Rotter, J I, additional, Whitsel, E A, additional, Psaty, B M, additional, and Avery, C L, additional

Published
2017
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7. Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group

Author

Floyd, J S, primary, Sitlani, C M, additional, Avery, C L, additional, Noordam, R, additional, Li, X, additional, Smith, A V, additional, Gogarten, S M, additional, Li, J, additional, Broer, L, additional, Evans, D S, additional, Trompet, S, additional, Brody, J A, additional, Stewart, J D, additional, Eicher, J D, additional, Seyerle, A A, additional, Roach, J, additional, Lange, L A, additional, Lin, H J, additional, Kors, J A, additional, Harris, T B, additional, Li-Gao, R, additional, Sattar, N, additional, Cummings, S R, additional, Wiggins, K L, additional, Napier, M D, additional, Stürmer, T, additional, Bis, J C, additional, Kerr, K F, additional, Uitterlinden, A G, additional, Taylor, K D, additional, Stott, D J, additional, de Mutsert, R, additional, Launer, L J, additional, Busch, E L, additional, Méndez-Giráldez, R, additional, Sotoodehnia, N, additional, Soliman, E Z, additional, Li, Y, additional, Duan, Q, additional, Rosendaal, F R, additional, Slagboom, P E, additional, Wilhelmsen, K C, additional, Reiner, A P, additional, Chen, Y-DI, additional, Heckbert, S R, additional, Kaplan, R C, additional, Rice, K M, additional, Jukema, J W, additional, Johnson, A D, additional, Liu, Y, additional, Mook-Kanamori, D O, additional, Gudnason, V, additional, Wilson, J G, additional, Rotter, J I, additional, Laurie, C C, additional, Psaty, B M, additional, Whitsel, E A, additional, Cupples, L A, additional, and Stricker, B H, additional

Published
2016
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8. Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology

Author

Seyerle, A A, Sitlani, C M, Noordam, R, Gogarten, S M, Li, J, Li, X, Evans, D S, Sun, F, Laaksonen, M A, Isaacs, A, Kristiansson, K, Highland, H M, Stewart, J D, Harris, T B, Trompet, S, Bis, J C, Peloso, G M, Brody, J A, Broer, L, Busch, E L, Duan, Q, Stilp, A M, O'Donnell, C J, Macfarlane, P W, Floyd, J S, Kors, J A, Lin, H J, Li-Gao, R, Sofer, T, Méndez-Giráldez, R, Cummings, S R, Heckbert, S R, Hofman, A, Ford, I, Li, Y, Launer, L J, Porthan, K, Newton-Cheh, C, Napier, M D, Kerr, K F, Reiner, A P, Rice, K M, Roach, J, Buckley, B M, Soliman, E Z, de Mutsert, R, Sotoodehnia, N, Uitterlinden, A G, North, K E, Lee, C R, Gudnason, V, Stürmer, T, Rosendaal, F R, Taylor, K D, Wiggins, K L, Wilson, J G, Chen, Y-DI, Kaplan, R C, Wilhelmsen, K, Cupples, L A, Salomaa, V, van Duijn, C, Jukema, J W, Liu, Y, Mook-Kanamori, D O, Lange, L A, Vasan, R S, Smith, A V, Stricker, B H, Laurie, C C, Rotter, J I, Whitsel, E A, Psaty, B M, and Avery, C L

Abstract

Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, trans-ethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populations (N=78?199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment. Although no loci achieved genome-wide significance (P<5 × 10-8), we found suggestive evidence (P<5 × 10-6) for SNPs modifying the thiazide-QT association at 22 loci, including ion transport loci (for example, NELL1, KCNQ3). The biologic plausibility of our suggestive results and simulations demonstrating modest power to detect interaction effects at genome-wide significant levels indicate that larger studies and innovative statistical methods are warranted in future efforts evaluating thiazide–SNP interactions.

Published
2018
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9. The association of statin therapy with the risk of recurrent venous thrombosis.

Author

Smith NL, Harrington LB, Blondon M, Wiggins KL, Floyd JS, Sitlani CM, McKnight B, Larson EB, Rosendaal FR, Heckbert SR, and Psaty BM

Subjects
Administration, Oral, Adolescent, Adult, Aged, Aged, 80 and over, Anticoagulants therapeutic use, Cardiovascular Diseases therapy, Contraceptives, Oral therapeutic use, Estrogens therapeutic use, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prevalence, Proportional Hazards Models, Pulmonary Embolism drug therapy, Recurrence, Risk Factors, Thrombosis drug therapy, Venous Thrombosis metabolism, Young Adult, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Venous Thrombosis drug therapy, Venous Thrombosis prevention & control
Abstract

Unlabelled: Essentials A lowered risk of recurrent venous thrombosis (VT) with statin treatment is controversial. Among observational inception cohort of 2,798 adults with incident VT, 457 had recurrent VT. Time-to-event models with time-varying statin use and adjustment for potential confounders was used for analysis. Compared to nonuse, current statin use was associated with 26% lower risk of recurrent VT. Click to hear Prof. Büller's perspective on Anticoagulant Therapy in the Treatment of Venous Thromboembolism, Summary: Background Meta-analyses of randomized controlled trials suggest that treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) lowers the risk of incident venous thrombosis (VT), particularly among those without prevalent clinical cardiovascular disease (CVD). Whether this is true for the prevention of recurrent VT is debated. We used an observational inception cohort to estimate the association of current statin use with the risk of recurrent VT. Methods and Results The study setting was a large healthcare organization with detailed medical record and pharmacy information at cohort entry and throughout follow-up. We followed 2798 subjects 18-89 years of age who experienced a validated incident VT between January 1, 2002, and December 31, 2010, for a first recurrent VT, validated by medical record review. During follow-up, 457 (16%) developed a first recurrent VT. In time-to-event models incorporating time-varying statin use and adjusting for potential confounders, current statin use was associated with a 26% lower risk of recurrent VT: hazard ratio 0.74, 95% confidence interval 0.59-0.94. Among cohort members free of CVD (n = 2134), current statin use was also associated with a lower risk (38%) of recurrent VT: hazard ratio 0.62, 95% confidence interval 0.45-0.85. We found similar results when restricting to new users of statins and in subgroups of different statin types and doses. Conclusions In a population-based cohort of subjects who had experienced an incident VT, statin use, compared with nonuse, was associated with a clinically relevant lower risk of recurrent VT. These findings suggest a potential secondary benefit of statins among patients who have experienced an incident VT., (© 2016 International Society on Thrombosis and Haemostasis.)

Published
2016
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