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Author Notes:

Digna R. Velez Edwards, PhD, MS, Institute of Medicine and Public Health, Departments of Obstetrics and Gynecology and Biomedical Informatics, Vanderbilt Genetics Institute, Vanderbilt Epidemiology Center, 2525 West End Avenue, Suite 600, Nashville, TN 37203, USA. Tel: +1 615 322 1288; fax: +1 615 936 24 03. Email: digna.r.velez.edwards@vumc.org

J.M.K. wrote the manuscript and researched and analyzed the data. J.N.H., A.G., and E.S.T. researched data, contributed to data analysis, and reviewed and edited the manuscript. C.P.K., Y.V.S., P.W.F.W., and C.J.O. contributed to study design and reviewed and edited the manuscript. T.L.E., A.M.H., and D.R.V.E. designed the study, assisted with data analysis, and reviewed and edited the manuscript. D.R.V.E. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

L.E. and D.R.V.E. were supported by NIH/NHLBI grant HL121429. This research is based on data from the Million Veteran Program, Office of Research and Development, Veterans Health Administration, and was supported by funding from the Department of Veterans Affairs Office of Research and Development, Million Veteran Program Grant I01BX003360 to A.M.H. J.M.K. is supported by the Vanderbilt Genomic Medicine Training Program, funded by T32HG008341 (PI: JC Denny). J.N.H. is supported by the Vanderbilt Molecular and Genetic Epidemiology of Cancer (MAGEC) training program, funded by T32C7A160056 (PI: X-O Shu). The work was in part supported by the Building Interdisciplinary Research Careers in Women’s Healthcareer development program’s 2K12HD043483-17 (PI: KE Hartmann) to A.G. Y.V.S. and P.W.F.W. were funded by the Veterans Affairs Merit Award I01-01BX003340 (PI: PWF Wilson). Y.V.S. was supported by NIH grant NR013520. This work was supported using resources and facilities of the VA Informatics and Computing Infrastructure (VINCI), VA HSR RES 13-457. This publication does not represent the views of the Department of Veterans Affairs or the United States Government.

Subjects:

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Peripheral Vascular Disease
  • Cardiovascular System & Cardiology
  • admixture
  • blood pressure
  • genetic ancestry
  • hypertension
  • resistant hypertension
  • GENOME-WIDE ASSOCIATION
  • CARDIOVASCULAR RISK-FACTORS
  • BLOOD-PRESSURE
  • AFRICAN-AMERICANS
  • IMPUTATION
  • BIOBANK

Associations of biogeographic ancestry with hypertension traits

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Journal Title:

JOURNAL OF HYPERTENSION

Volume:

Volume 39, Number 4

Publisher:

, Pages 633-642

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Objectives:Ethnic disparities in hypertension prevalence are well documented, though the influence of genetic ancestry is unclear. The aim of this study was to evaluate associations of geographic genetic ancestry with hypertension and underlying blood pressure traits.Methods:We tested genetically inferred ancestry proportions from five 1000 Genomes reference populations (GBR, PEL, YRI, CHB, and LWK) for association with four continuous blood pressure (BP) traits (SBP, DBP, PP, MAP) and the dichotomous outcomes hypertension and apparent treatment-resistant hypertension in 220 495 European American, 59 927 African American, and 21 273 Hispanic American individuals from the Million Veteran Program. Ethnicity stratified results were meta-analyzed to report effect estimates per 10% difference for a given ancestry proportion in all samples.Results:Percentage GBR was negatively associated with BP (P = 2.13 × 10-19, 7.92 × 10-8, 4.41 × 10-11, and 3.57 × 10-13 for SBP, DBP, PP, and MAP, respectively; coefficient range -0.10 to -0.21 mmHg per 10% increase in ancestry proportion) and was protective against hypertension [P = 2.59 × 10-5, odds ratio (OR) = 0.98] relative to other ancestries. YRI percentage was positively associated with BP (P = 1.63 × 10-23, 1.94 × 10-26, 0.012, and 3.26 × 10-29 for SBP, DBP, PP, and MAP, respectively; coefficient range 0.06-0.32 mmHg per 10% increase in ancestry proportion) and was positively associated with hypertension risk (P = 3.10 × 10-11, OR = 1.04) and apparent treatment-resistant hypertension risk (P = 1.86 × 10-4, OR = 1.04) compared with other ancestries. Percentage PEL was inversely associated with DBP (P = 2.84 × 10-5, beta = -0.11 mmHg per 10% increase in ancestry proportion).Conclusion:These results demonstrate that risk for BP traits varies significantly by genetic ancestry. Our findings provide insight into the geographic origin of genetic factors underlying hypertension risk and establish that a portion of BP trait ethnic disparities are because of genetic differences between ancestries.

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This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/rdf).
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