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Genome-wide meta-analysis of variant-by-diuretic interactions as modulators of lipid traits in persons of European and African ancestry.
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; Whitsel, E A.
Afiliação
  • de Las Fuentes L; Cardiovascular Division, Department of Medicine, Washington University, St. Louis, MO, USA. lfuentes@wustl.edu.
  • Sung YJ; Division of Biostatistics, Washington University, St. Louis, MO, USA.
  • Sitlani CM; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Avery CL; Gillings School of Global Public Health, Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
  • Bartz TM; Cardiovascular Health Research Unit, Departments of Medicine and Biostatistics, University of Washington, Seattle, WA, USA.
  • Keyser C; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Evans DS; Research Institute, California Pacific Medical Center, San Francisco, CA, USA.
  • Li X; Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Musani SK; Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
  • Ruiter R; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Smith AV; Icelandic Heart Association, Kopavogur, Iceland.
  • Sun F; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
  • Trompet S; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
  • Xu H; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
  • Arnett DK; Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
  • Bis JC; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
  • Broeckel U; Dean's Office, University of Kentucky College of Public Health, Lexington, KY, USA.
  • Busch EL; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Chen YI; Section of Genomic Pediatrics, Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Correa A; Channing Division of Network Medicine, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
  • Cummings SR; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Floyd JS; Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Ford I; Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
  • Guo X; Research Institute, California Pacific Medical Center, San Francisco, CA, USA.
  • Harris TB; Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, WA, USA.
  • Ikram MA; Robertson Center for biostatistics, University of Glasgow, Glasgow, UK.
  • Lange L; Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Launer LJ; Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, MD, USA.
  • Reiner AP; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Schwander K; Department of Genetics, University of Colorado, Denver, Denver, CO, USA.
  • Smith NL; Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, MD, USA.
  • Sotoodehnia N; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Stewart JD; School of Public Health, Department of Epidemiology, University of Washington, Seattle, WA, USA.
  • Stott DJ; Division of Biostatistics, Washington University, St. Louis, MO, USA.
  • Stürmer T; Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, WA, USA.
  • Taylor KD; Seattle Epidemiologic Research and Information Center (ERIC), VA Cooperative Studies Program, VA Puget Sound Health Care System, Seattle, WA, USA.
  • Uitterlinden A; Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, WA, USA.
  • Vasan RS; Cardiology, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Wiggins KL; Gillings School of Global Public Health, Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
  • Cupples LA; Carolina Population Center, University of North Carolina, Chapel Hill, NC, USA.
  • Gudnason V; Institute of cardiovascular and medical sciences, Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom.
  • Heckbert SR; Gillings School of Global Public Health, Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
  • Jukema JW; Center for Pharmacoepidemiology, University of North Carolina, Chapel Hill, NC, USA.
  • Liu Y; Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Psaty BM; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Rao DC; The Framingham Heart Study, Framingham, MA, USA.
  • Rotter JI; Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
  • Stricker B; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Wilson JG; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
  • Whitsel EA; The Framingham Heart Study, Framingham, MA, USA.
Pharmacogenomics J ; 20(3): 482-493, 2020 06.
Article em En | MEDLINE | ID: mdl-31806883
ABSTRACT
Hypertension (HTN) is a significant risk factor for cardiovascular morbidity and mortality. Metabolic abnormalities, including adverse cholesterol and triglycerides (TG) profiles, are frequent comorbid findings with HTN and contribute to cardiovascular disease. Diuretics, which are used to treat HTN and heart failure, have been associated with worsening of fasting lipid concentrations. Genome-wide meta-analyses with 39,710 European-ancestry (EA) individuals and 9925 African-ancestry (AA) individuals were performed to identify genetic variants that modify the effect of loop or thiazide diuretic use on blood lipid concentrations. Both longitudinal and cross sectional data were used to compute cohort-specific interaction results, which were then combined through meta-analysis in each ancestry. These ancestry-specific results were further combined through trans-ancestry meta-analysis. Analysis of EA data identified two genome-wide significant (p < 5 × 10-8) loci with single nucleotide variant (SNV)-loop diuretic interaction on TG concentrations (including COL11A1). Analysis of AA data identified one genome-wide significant locus adjacent to BMP2 with SNV-loop diuretic interaction on TG concentrations. Trans-ancestry analysis strengthened evidence of association for SNV-loop diuretic interaction at two loci (KIAA1217 and BAALC). There were few significant SNV-thiazide diuretic interaction associations on TG concentrations and for either diuretic on cholesterol concentrations. Several promising loci were identified that may implicate biologic pathways that contribute to adverse metabolic side effects from diuretic therapy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Negro ou Afro-Americano / População Branca / Diuréticos / Hipertensão Tipo de estudo: Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Negro ou Afro-Americano / População Branca / Diuréticos / Hipertensão Tipo de estudo: Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article