Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium

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Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease : A Pharmacogenomics Study from the CHARGE Consortium. / Bis, Joshua C; Sitlani, Colleen; Irvin, Ryan; Avery, Christy L; Smith, Albert Vernon; Sun, Fangui; Evans, Daniel S; Musani, Solomon K; Li, Xiaohui; Trompet, Stella; Krijthe, Bouwe P; Harris, Tamara B; Quibrera, P Miguel; Brody, Jennifer A; Demissie, Serkalem; Davis, Barry R; Wiggins, Kerri L; Tranah, Gregory J; Lange, Leslie A; Sotoodehnia, Nona; Stott, David J; Franco, Oscar H; Launer, Lenore J; Stürmer, Til; Taylor, Kent D; Cupples, L Adrienne; Eckfeldt, John H; Smith, Nicholas L; Liu, Yongmei; Wilson, James G; Heckbert, Susan R; Buckley, Brendan M; Ikram, M Arfan; Boerwinkle, Eric; Chen, Yii-Der Ida; de Craen, Anton J M; Uitterlinden, Andre G; Rotter, Jerome I; Ford, Ian; Hofman, Albert; Sattar, Naveed; Slagboom, P Eline; Westendorp, Rudi G J; Gudnason, Vilmundur; Vasan, Ramachandran S; Lumley, Thomas; Cummings, Steven R; Taylor, Herman A; Post, Wendy; Jukema, J Wouter; Stricker, Bruno H; Whitsel, Eric A; Psaty, Bruce M; Arnett, Donna.

In: PLOS ONE, Vol. 10, No. 10, e0140496, 30.10.2015, p. 1-13.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Bis, JC, Sitlani, C, Irvin, R, Avery, CL, Smith, AV, Sun, F, Evans, DS, Musani, SK, Li, X, Trompet, S, Krijthe, BP, Harris, TB, Quibrera, PM, Brody, JA, Demissie, S, Davis, BR, Wiggins, KL, Tranah, GJ, Lange, LA, Sotoodehnia, N, Stott, DJ, Franco, OH, Launer, LJ, Stürmer, T, Taylor, KD, Cupples, LA, Eckfeldt, JH, Smith, NL, Liu, Y, Wilson, JG, Heckbert, SR, Buckley, BM, Ikram, MA, Boerwinkle, E, Chen, Y-DI, de Craen, AJM, Uitterlinden, AG, Rotter, JI, Ford, I, Hofman, A, Sattar, N, Slagboom, PE, Westendorp, RGJ, Gudnason, V, Vasan, RS, Lumley, T, Cummings, SR, Taylor, HA, Post, W, Jukema, JW, Stricker, BH, Whitsel, EA, Psaty, BM & Arnett, D 2015, 'Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium', PLOS ONE, vol. 10, no. 10, e0140496, pp. 1-13. https://doi.org/10.1371/journal.pone.0140496

APA

Bis, J. C., Sitlani, C., Irvin, R., Avery, C. L., Smith, A. V., Sun, F., ... Arnett, D. (2015). Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium. PLOS ONE, 10(10), 1-13. [e0140496]. https://doi.org/10.1371/journal.pone.0140496

Vancouver

Bis JC, Sitlani C, Irvin R, Avery CL, Smith AV, Sun F et al. Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium. PLOS ONE. 2015 Oct 30;10(10):1-13. e0140496. https://doi.org/10.1371/journal.pone.0140496

Author

Bis, Joshua C ; Sitlani, Colleen ; Irvin, Ryan ; Avery, Christy L ; Smith, Albert Vernon ; Sun, Fangui ; Evans, Daniel S ; Musani, Solomon K ; Li, Xiaohui ; Trompet, Stella ; Krijthe, Bouwe P ; Harris, Tamara B ; Quibrera, P Miguel ; Brody, Jennifer A ; Demissie, Serkalem ; Davis, Barry R ; Wiggins, Kerri L ; Tranah, Gregory J ; Lange, Leslie A ; Sotoodehnia, Nona ; Stott, David J ; Franco, Oscar H ; Launer, Lenore J ; Stürmer, Til ; Taylor, Kent D ; Cupples, L Adrienne ; Eckfeldt, John H ; Smith, Nicholas L ; Liu, Yongmei ; Wilson, James G ; Heckbert, Susan R ; Buckley, Brendan M ; Ikram, M Arfan ; Boerwinkle, Eric ; Chen, Yii-Der Ida ; de Craen, Anton J M ; Uitterlinden, Andre G ; Rotter, Jerome I ; Ford, Ian ; Hofman, Albert ; Sattar, Naveed ; Slagboom, P Eline ; Westendorp, Rudi G J ; Gudnason, Vilmundur ; Vasan, Ramachandran S ; Lumley, Thomas ; Cummings, Steven R ; Taylor, Herman A ; Post, Wendy ; Jukema, J Wouter ; Stricker, Bruno H ; Whitsel, Eric A ; Psaty, Bruce M ; Arnett, Donna. / Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease : A Pharmacogenomics Study from the CHARGE Consortium. In: PLOS ONE. 2015 ; Vol. 10, No. 10. pp. 1-13.

Bibtex

@article{a064fec3caec43149f7bb57289eaba16,
title = "Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium",
abstract = "BACKGROUND: Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals.METHODS: Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases).RESULTS: Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction > 5.0×10-8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (Pinteraction ≥ 0.01). Our results suggest that there are no major pharmacogenetic influences of common SNPs on the relationship between blood pressure medications and the risk of incident CVD.",
author = "Bis, {Joshua C} and Colleen Sitlani and Ryan Irvin and Avery, {Christy L} and Smith, {Albert Vernon} and Fangui Sun and Evans, {Daniel S} and Musani, {Solomon K} and Xiaohui Li and Stella Trompet and Krijthe, {Bouwe P} and Harris, {Tamara B} and Quibrera, {P Miguel} and Brody, {Jennifer A} and Serkalem Demissie and Davis, {Barry R} and Wiggins, {Kerri L} and Tranah, {Gregory J} and Lange, {Leslie A} and Nona Sotoodehnia and Stott, {David J} and Franco, {Oscar H} and Launer, {Lenore J} and Til St{\"u}rmer and Taylor, {Kent D} and Cupples, {L Adrienne} and Eckfeldt, {John H} and Smith, {Nicholas L} and Yongmei Liu and Wilson, {James G} and Heckbert, {Susan R} and Buckley, {Brendan M} and Ikram, {M Arfan} and Eric Boerwinkle and Chen, {Yii-Der Ida} and {de Craen}, {Anton J M} and Uitterlinden, {Andre G} and Rotter, {Jerome I} and Ian Ford and Albert Hofman and Naveed Sattar and Slagboom, {P Eline} and Westendorp, {Rudi G J} and Vilmundur Gudnason and Vasan, {Ramachandran S} and Thomas Lumley and Cummings, {Steven R} and Taylor, {Herman A} and Wendy Post and Jukema, {J Wouter} and Stricker, {Bruno H} and Whitsel, {Eric A} and Psaty, {Bruce M} and Donna Arnett",
year = "2015",
month = "10",
day = "30",
doi = "10.1371/journal.pone.0140496",
language = "English",
volume = "10",
pages = "1--13",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

RIS

TY - JOUR

T1 - Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease

T2 - A Pharmacogenomics Study from the CHARGE Consortium

AU - Bis, Joshua C

AU - Sitlani, Colleen

AU - Irvin, Ryan

AU - Avery, Christy L

AU - Smith, Albert Vernon

AU - Sun, Fangui

AU - Evans, Daniel S

AU - Musani, Solomon K

AU - Li, Xiaohui

AU - Trompet, Stella

AU - Krijthe, Bouwe P

AU - Harris, Tamara B

AU - Quibrera, P Miguel

AU - Brody, Jennifer A

AU - Demissie, Serkalem

AU - Davis, Barry R

AU - Wiggins, Kerri L

AU - Tranah, Gregory J

AU - Lange, Leslie A

AU - Sotoodehnia, Nona

AU - Stott, David J

AU - Franco, Oscar H

AU - Launer, Lenore J

AU - Stürmer, Til

AU - Taylor, Kent D

AU - Cupples, L Adrienne

AU - Eckfeldt, John H

AU - Smith, Nicholas L

AU - Liu, Yongmei

AU - Wilson, James G

AU - Heckbert, Susan R

AU - Buckley, Brendan M

AU - Ikram, M Arfan

AU - Boerwinkle, Eric

AU - Chen, Yii-Der Ida

AU - de Craen, Anton J M

AU - Uitterlinden, Andre G

AU - Rotter, Jerome I

AU - Ford, Ian

AU - Hofman, Albert

AU - Sattar, Naveed

AU - Slagboom, P Eline

AU - Westendorp, Rudi G J

AU - Gudnason, Vilmundur

AU - Vasan, Ramachandran S

AU - Lumley, Thomas

AU - Cummings, Steven R

AU - Taylor, Herman A

AU - Post, Wendy

AU - Jukema, J Wouter

AU - Stricker, Bruno H

AU - Whitsel, Eric A

AU - Psaty, Bruce M

AU - Arnett, Donna

PY - 2015/10/30

Y1 - 2015/10/30

N2 - BACKGROUND: Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals.METHODS: Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases).RESULTS: Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction > 5.0×10-8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (Pinteraction ≥ 0.01). Our results suggest that there are no major pharmacogenetic influences of common SNPs on the relationship between blood pressure medications and the risk of incident CVD.

AB - BACKGROUND: Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals.METHODS: Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases).RESULTS: Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction > 5.0×10-8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (Pinteraction ≥ 0.01). Our results suggest that there are no major pharmacogenetic influences of common SNPs on the relationship between blood pressure medications and the risk of incident CVD.

U2 - 10.1371/journal.pone.0140496

DO - 10.1371/journal.pone.0140496

M3 - Journal article

VL - 10

SP - 1

EP - 13

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 10

M1 - e0140496

ER -

ID: 147133088