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 journalArticle

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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
Pages (from-to)106-112
Number of pages7
JournalPharmacogenomics Journal
Volume18
Issue number1
DOIs
Publication statusPublished - 01-01-2018

Fingerprint

Genome-Wide Association Study
Pharmacogenetics
Calcium Channel Blockers
Antihypertensive Agents
trandolapril
Quantitative Trait Loci
Meta-Analysis
Homozygote
Verapamil
Hispanic Americans
African Americans
Therapeutics
Joints
Alleles
Odds Ratio
Gene Expression

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Pharmacology

Cite this

Chang, S. W., McDonough, C. W., Gong, Y., Johnson, T. A., Tsunoda, T., Gamazon, E. R., ... Cooper-Dehoff, R. M. (2018). Genome-wide association study identifies pharmacogenomic loci linked with specific antihypertensive drug treatment and new-onset diabetes. Pharmacogenomics Journal, 18(1), 106-112. https://doi.org/10.1038/tpj.2016.67
Chang, S. W. ; McDonough, C. W. ; Gong, Y. ; Johnson, T. A. ; Tsunoda, T. ; Gamazon, E. R. ; Perera, M. A. ; Takahashi, A. ; Tanaka, T. ; Kubo, M. ; Pepine, C. J. ; Johnson, J. A. ; Cooper-Dehoff, R. M. / Genome-wide association study identifies pharmacogenomic loci linked with specific antihypertensive drug treatment and new-onset diabetes. In: Pharmacogenomics Journal. 2018 ; Vol. 18, No. 1. pp. 106-112.
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Chang, SW, McDonough, CW, Gong, Y, Johnson, TA, Tsunoda, T, Gamazon, ER, Perera, MA, Takahashi, A, Tanaka, T, Kubo, M, Pepine, CJ, Johnson, JA & Cooper-Dehoff, RM 2018, 'Genome-wide association study identifies pharmacogenomic loci linked with specific antihypertensive drug treatment and new-onset diabetes', Pharmacogenomics Journal, vol. 18, no. 1, pp. 106-112. https://doi.org/10.1038/tpj.2016.67

Genome-wide association study identifies pharmacogenomic loci linked with specific antihypertensive drug treatment and new-onset diabetes. / Chang, S. W.; McDonough, C. W.; Gong, Y.; Johnson, T. A.; Tsunoda, T.; Gamazon, E. R.; Perera, M. A.; Takahashi, A.; Tanaka, T.; Kubo, M.; Pepine, C. J.; Johnson, J. A.; Cooper-Dehoff, R. M.

In: Pharmacogenomics Journal, Vol. 18, No. 1, 01.01.2018, p. 106-112.

Research output: Contribution to journalArticle

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AU - Johnson, T. A.

AU - Tsunoda, T.

AU - Gamazon, E. R.

AU - Perera, M. A.

AU - Takahashi, A.

AU - Tanaka, T.

AU - Kubo, M.

AU - Pepine, C. J.

AU - Johnson, J. A.

AU - Cooper-Dehoff, R. M.

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