Genome-wide meta-analysis of SNP and antihypertensive medication interactions on left ventricular traits in African Americans

Research output: Contribution to journalArticle

Authors

  • Anh N. Do
  • Wei Zhao
  • Abigail S. Baldridge
  • Laura M. Raffield
  • Kerri L. Wiggins
  • Hemant K. Tiwari
  • Nita Limdi
  • Degui Zhi
  • Colleen M. Sitlani
  • Kent D. Taylor
  • Bruce M. Psaty
  • Jennifer A. Brody
  • Donald Lloyd-Jones
  • Leslie A. Lange
  • James G. Wilson
  • Jennifer A. Smith
  • Sharon L.R. Kardia
  • Thomas H. Mosley
  • Ramachandran S. Vasan

External Institution(s)

  • University of Alabama at Birmingham
  • University of Michigan, Ann Arbor
  • Northwestern University
  • University of North Carolina at Chapel Hill
  • University of Washington
  • University of Texas Health Science Center at Houston
  • Har-borview Medical Center
  • Kaiser Permanente
  • University of Colorado Denver
  • University of Mississippi
  • Boston University

Details

Original languageEnglish (US)
Article numbere00788
JournalMolecular Genetics and Genomic Medicine
Volume7
Issue number10
StatusPublished - Oct 1 2019
Peer-reviewedYes

Abstract

Background: Left ventricular (LV) hypertrophy affects up to 43% of African Americans (AAs). Antihypertensive treatment reduces LV mass (LVM). However, interindividual variation in LV traits in response to antihypertensive treatments exists. We hypothesized that genetic variants may modify the association of antihypertensive treatment class with LV traits measured by echocardiography. Methods: We evaluated the main effects of the three most common antihypertensive treatments for AAs as well as the single nucleotide polymorphism (SNP)-by-drug interaction on LVM and relative wall thickness (RWT) in 2,068 participants across five community-based cohorts. Treatments included thiazide diuretics (TDs), angiotensin converting enzyme inhibitors (ACE-Is), and dihydropyridine calcium channel blockers (dCCBs) and were compared in a pairwise manner. We performed fixed effects inverse variance weighted meta-analyses of main effects of drugs and 2.5 million SNP-by-drug interaction estimates. Results: We observed that dCCBs versus TDs were associated with higher LVM after adjusting for covariates (p = 0.001). We report three SNPs at a single locus on chromosome 20 that modified the association between RWT and treatment when comparing dCCBs to ACE-Is with consistent effects across cohorts (smallest p = 4.7 × 10−8, minor allele frequency range 0.09–0.12). This locus has been linked to LV hypertrophy in a previous study. A marginally significant locus in BICD1 (rs326641) was validated in an external population. Conclusions: Our study identified one locus having genome-wide significant SNP-by-drug interaction effect on RWT among dCCB users in comparison to ACE-I users. Upon additional validation in future studies, our findings can enhance the precision of medical approaches in hypertension treatment.

    Research areas

  • GWAS, antihypertensive treatment, left ventricular trait, pharmacogenetics

Citation formats

APA

Do, A. N., Zhao, W., Baldridge, A. S., Raffield, L. M., Wiggins, K. L., Shah, S. J., ... Irvin, M. R. (2019). Genome-wide meta-analysis of SNP and antihypertensive medication interactions on left ventricular traits in African Americans. Molecular Genetics and Genomic Medicine, 7(10), [e00788]. https://doi.org/10.1002/mgg3.788

Harvard

Do, AN, Zhao, W, Baldridge, AS, Raffield, LM, Wiggins, KL, Shah, SJ, Aslibekyan, S, Tiwari, HK, Limdi, N, Zhi, D, Sitlani, CM, Taylor, KD, Psaty, BM, Sotoodehnia, N, Brody, JA, Rasmussen-Torvik, LJ, Lloyd-Jones, D, Lange, LA, Wilson, JG, Smith, JA, Kardia, SLR, Mosley, TH, Vasan, RS, Arnett, DK & Irvin, MR 2019, 'Genome-wide meta-analysis of SNP and antihypertensive medication interactions on left ventricular traits in African Americans', Molecular Genetics and Genomic Medicine, vol. 7, no. 10, e00788. https://doi.org/10.1002/mgg3.788