DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Diabetes in response to antihypertensive drug treatment (treatment strategy interaction). The EFO term response to antihypertensive drug, diabetes mellitus, hypertension, response to beta blocker, response to calcium channel blocker was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: response to antihypertensive drug, diabetes mellitus, hypertension, response to beta blocker, response to calcium channel blocker

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

SW Chang, CW McDonough, Y Gong, TA Johnson, T Tsunoda, ER Gamazon, MA Perera, A Takahashi, T Tanaka, M Kubo, CJ Pepine, JA Johnson, RM Cooper-DeHoff

TITLE:

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

JOURNAL:

The pharmacogenomics journal Sep 2016, Vol None, pp. None

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.The Pharmacogenomics Journal advance online publication, 27 September 2016; doi:10.1038/tpj.2016.67. PUBMED: 27670767
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