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 language | English |
|---|---|
| Pages (from-to) | 106-112 |
| Number of pages | 7 |
| Journal | Pharmacogenomics Journal |
| Volume | 18 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 01-01-2018 |
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All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Genetics
- Pharmacology
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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 journal › Article
TY - JOUR
T1 - Genome-wide association study identifies pharmacogenomic loci linked with specific antihypertensive drug treatment and new-onset diabetes
AU - Chang, S. W.
AU - McDonough, C. W.
AU - Gong, Y.
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.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84988703075&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84988703075&partnerID=8YFLogxK
U2 - 10.1038/tpj.2016.67
DO - 10.1038/tpj.2016.67
M3 - Article
C2 - 27670767
AN - SCOPUS:84988703075
VL - 18
SP - 106
EP - 112
JO - Pharmacogenomics Journal
JF - Pharmacogenomics Journal
SN - 1470-269X
IS - 1
ER -