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

当前位置： X-MOL 学术 › Pharmacogenomics J. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Genome-wide meta-analysis of variant-by-diuretic interactions as modulators of lipid traits in persons of European and African ancestry.
The Pharmacogenomics Journal ( IF 2.9 ) Pub Date : 2019-12-06 , DOI: 10.1038/s41397-019-0132-y
L de Las Fuentes ₁ , Y J Sung ₂ , C M Sitlani ₃ , C L Avery ₄ , T M Bartz ₅ , C de Keyser ₆ , D S Evans ₇ , X Li ₈ , S K Musani ₉ , R Ruiter ₆ , A V Smith _{10,

11} , F Sun ₁₂ , S Trompet _{13,

14} , H Xu ₁₂ , D K Arnett ₁₅ , J C Bis ₃ , U Broeckel ₁₆ , E L Busch _{17,

18} , Y-D I Chen ₈ , A Correa ₉ , S R Cummings ₇ , J S Floyd ₁₉ , I Ford ₂₀ , X Guo ₈ , T B Harris ₂₁ , M A Ikram ₆ , L Lange ₂₂ , L J Launer ₂₁ , A P Reiner _{23,

24} , K Schwander ₂ , N L Smith _{25,

26} , N Sotoodehnia _{19,

27} , J D Stewart _{4,

28} , D J Stott ₂₉ , T Stürmer _{4,

30} , K D Taylor ₈ , A Uitterlinden ₆ , R S Vasan _{31,

32} , K L Wiggins ₃ , L A Cupples _{12,

31} , V Gudnason _{10,

11} , S R Heckbert ₂₅ , J W Jukema _{13,

33} , Y Liu ₃₄ , B M Psaty _{35,

36} , D C Rao ₂ , J I Rotter ₈ , B Stricker ₆ , J G Wilson ₃₇ , E A Whitsel _{4,

38}

Affiliation

Cardiovascular Division, Department of Medicine, Washington University, St. Louis, MO, USA.
Division of Biostatistics, Washington University, St. Louis, MO, USA.
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Gillings School of Global Public Health, Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
Cardiovascular Health Research Unit, Departments of Medicine and Biostatistics, University of Washington, Seattle, WA, USA.
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Research Institute, California Pacific Medical Center, San Francisco, CA, USA.
Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
Icelandic Heart Association, Kopavogur, Iceland.
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
Dean's Office, University of Kentucky College of Public Health, Lexington, KY, USA.
Section of Genomic Pediatrics, Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Channing Division of Network Medicine, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, WA, USA.
Robertson Center for biostatistics, University of Glasgow, Glasgow, UK.
Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, MD, USA.
Department of Genetics, University of Colorado, Denver, Denver, CO, USA.
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
School of Public Health, Department of Epidemiology, University of Washington, Seattle, WA, USA.
Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, WA, USA.
Seattle Epidemiologic Research and Information Center (ERIC), VA Cooperative Studies Program, VA Puget Sound Health Care System, Seattle, WA, USA.
Cardiology, Department of Medicine, University of Washington, Seattle, WA, USA.
Carolina Population Center, University of North Carolina, Chapel Hill, NC, USA.
Institute of cardiovascular and medical sciences, Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom.
Center for Pharmacoepidemiology, University of North Carolina, Chapel Hill, NC, USA.
The Framingham Heart Study, Framingham, MA, USA.
Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
Division of Public Health Sciences, Department of Epidemiology and Prevention, Wake Forest University, Winston-, Salem, NC, USA.
Cardiovascular Health Research Unit, Departments of Epidemiology, Medicine, and Health Services, University of Washington, Seattle, WA, USA.
Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
Biophysics and Physiology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
School of Medicine, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.

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.

中文翻译：

对欧洲和非洲血统的人的脂质特征调节剂的变体与利尿剂相互作用的全基因组荟萃分析。

高血压（HTN）是心血管疾病发病和死亡的重要危险因素。代谢异常，包括不良胆固醇和甘油三酯 (TG) 谱，是 HTN 常见的合并症，并导致心血管疾病。用于治疗高血压和心力衰竭的利尿剂与空腹血脂浓度恶化有关。对 39,710 名欧洲血统 (EA) 个体和 9925 名非洲血统 (AA) 个体进行全基因组荟萃分析，以确定改变袢利尿剂或噻嗪类利尿剂使用对血脂浓度影响的遗传变异。纵向和横向数据都用于计算特定队列的相互作用结果，然后通过每个祖先的荟萃分析将其合并。这些特定于血统的结果通过跨血统荟萃分析进一步结合起来。 EA 数据分析确定了两个全基因组显着 (p < 5 × 10-8) 位点，其与 TG 浓度（包括 COL11A1）的单核苷酸变异 (SNV) 环利尿相互作用。 AA 数据分析确定了与 BMP2 相邻的一个全基因组显着位点，该位点与 SNV 环利尿剂对 TG 浓度有相互作用。跨祖先分析强化了两个位点（KIAA1217 和 BAALC）SNV 环利尿相互作用关联的证据。 SNV-噻嗪类利尿剂与 TG 浓度以及任一利尿剂与胆固醇浓度之间几乎没有显着的相互作用关联。确定了几个有希望的位点，这些位点可能涉及导致利尿治疗不良代谢副作用的生物途径。

更新日期：2019-12-06

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文