Genome-wide association study identifies pharmacogenomic loci linked with specific antihypertensive drug treatment and new-onset diabetes

S. W. Chang, C. W. McDonough, Y. Gong, T. A. Johnson, T. Tsunoda, E. R. Gamazon, M. A. Perera, A. Takahashi, T. Tanaka, M. Kubo, C. J. Pepine, J. A. Johnson, R. M. Cooper-DeHoff

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

We conducted a discovery genome-wide association study with expression quantitative trait loci (eQTL) annotation of new-onset diabetes (NOD) among European Americans, who were exposed to a calcium channel blocker-based strategy (CCB strategy) or a β-blocker-based strategy (β-blocker strategy) in the INternational VErapamil SR Trandolapril STudy. Replication of the top signal from the SNP∗treatment interaction analysis was attempted in Hispanic and African Americans, and a joint meta-analysis was performed (total 334 NOD cases and 806 matched controls). PLEKHH2 rs11124945 at 2p21 interacted with antihypertensive exposure for NOD (meta-analysis P=5.3 × 10 ' ' 8). rs11124945 G allele carriers had lower odds for NOD when exposed to the β-blocker strategy compared with the CCB strategy (Odds ratio OR=0.38(0.24' '0.60), P=4.0 × 10 ' ' 5), whereas A/A homozygotes exposed to the β-blocker strategy had increased odds for NOD compared with the CCB strategy (OR=2.02(1.39' '2.92), P=2.0 × 10 ' ' 4). eQTL annotation of the 2p21 locus provides functional support for regulating gene expression.

Original languageEnglish (US)
Pages (from-to)106-112
Number of pages7
JournalPharmacogenomics Journal
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2018

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

Fingerprint Dive into the research topics of 'Genome-wide association study identifies pharmacogenomic loci linked with specific antihypertensive drug treatment and new-onset diabetes'. Together they form a unique fingerprint.

Cite this