The Experts below are selected from a list of 234 Experts worldwide ranked by ideXlab platform
Christy L. Avery - One of the best experts on this subject based on the ideXlab platform.
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a genome wide interaction analysis of tricyclic Tetracyclic Antidepressants and rr and qt intervals a pharmacogenomics study from the cohorts for heart and aging research in genomic epidemiology charge consortium
Journal of Medical Genetics, 2017Co-Authors: Christy L. Avery, Colleen M. Sitlani, Raymond Noordam, James D Stewart, Stephanie M Gogarten, Kerri L Wiggins, Stella Trompet, Helen R Warren, Fangui SunAbstract:Background Increased heart rate and a prolonged QT interval are important risk factors for cardiovascular morbidity and mortality, and can be influenced by the use of various medications, including tricyclic/Tetracyclic Antidepressants (TCAs). We aim to identify genetic loci that modify the association between TCA use and RR and QT intervals. Methods and results We conducted race/ethnic-specific genome-wide interaction analyses (with HapMap phase II imputed reference panel imputation) of TCAs and resting RR and QT intervals in cohorts of European (n=45 706; n=1417 TCA users), African (n=10 235; n=296 TCA users) and Hispanic/Latino (n=13 808; n=147 TCA users) ancestry, adjusted for clinical covariates. Among the populations of European ancestry, two genome-wide significant loci were identified for RR interval: rs6737205 in BRE (β=56.3, p interaction =3.9e −9 ) and rs9830388 in UBE2E2 (β=25.2, p interaction =1.7e −8 ). In Hispanic/Latino cohorts, rs2291477 in TGFBR3 significantly modified the association between TCAs and QT intervals (β=9.3, p interaction =2.55e −8 ). In the meta-analyses of the other ethnicities, these loci either were excluded from the meta-analyses (as part of quality control), or their effects did not reach the level of nominal statistical significance (p interaction >0.05). No new variants were identified in these ethnicities. No additional loci were identified after inverse-variance-weighted meta-analysis of the three ancestries. Conclusions Among Europeans, TCA interactions with variants in BRE and UBE2E2 were identified in relation to RR intervals. Among Hispanic/Latinos, variants in TGFBR3 modified the relation between TCAs and QT intervals. Future studies are required to confirm our results.
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Drug–gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval
The Pharmacogenomics Journal, 2014Co-Authors: Christy L. Avery, Colleen M. Sitlani, Dan E. Arking, Donna K. Arnett, Joshua C. Bis, Eric Boerwinkle, Brendan M. Buckley, A.j.m. De Craen, Y-d Ida Chen, Mark EijgelsheimAbstract:Variability in response to drug use is common and heritable, suggesting that genome-wide pharmacogenomics studies may help explain the ‘missing heritability’ of complex traits. Here, we describe four independent analyses in 33 781 participants of European ancestry from 10 cohorts that were designed to identify genetic variants modifying the effects of drugs on QT interval duration (QT). Each analysis cross-sectionally examined four therapeutic classes: thiazide diuretics (prevalence of use=13.0%), tri/Tetracyclic Antidepressants (2.6%), sulfonylurea hypoglycemic agents (2.9%) and QT-prolonging drugs as classified by the University of Arizona Center for Education and Research on Therapeutics (4.4%). Drug–gene interactions were estimated using covariable-adjusted linear regression and results were combined with fixed-effects meta-analysis. Although drug–single-nucleotide polymorphism (SNP) interactions were biologically plausible and variables were well-measured, findings from the four cross-sectional meta-analyses were null ( P _interaction>5.0 × 10^−8). Simulations suggested that additional efforts, including longitudinal modeling to increase statistical power, are likely needed to identify potentially important pharmacogenomic effects.
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Drug-gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval.
The pharmacogenomics journal, 2013Co-Authors: Christy L. Avery, Colleen M. Sitlani, Dan E. Arking, Donna K. Arnett, Joshua C. Bis, Eric Boerwinkle, Brendan M. Buckley, Y.-d. Ida Chen, A.j.m. De Craen, Mark EijgelsheimAbstract:Variability in response to drug use is common and heritable, suggesting that genome-wide pharmacogenomics studies may help explain the 'missing heritability' of complex traits. Here, we describe four independent analyses in 33 781 participants of European ancestry from 10 cohorts that were designed to identify genetic variants modifying the effects of drugs on QT interval duration (QT). Each analysis cross-sectionally examined four therapeutic classes: thiazide diuretics (prevalence of use=13.0%), tri/Tetracyclic Antidepressants (2.6%), sulfonylurea hypoglycemic agents (2.9%) and QT-prolonging drugs as classified by the University of Arizona Center for Education and Research on Therapeutics (4.4%). Drug-gene interactions were estimated using covariable-adjusted linear regression and results were combined with fixed-effects meta-analysis. Although drug-single-nucleotide polymorphism (SNP) interactions were biologically plausible and variables were well-measured, findings from the four cross-sectional meta-analyses were null (Pinteraction>5.0 × 10(-8)). Simulations suggested that additional efforts, including longitudinal modeling to increase statistical power, are likely needed to identify potentially important pharmacogenomic effects.
Colleen M. Sitlani - One of the best experts on this subject based on the ideXlab platform.
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a genome wide interaction analysis of tricyclic Tetracyclic Antidepressants and rr and qt intervals a pharmacogenomics study from the cohorts for heart and aging research in genomic epidemiology charge consortium
Journal of Medical Genetics, 2017Co-Authors: Christy L. Avery, Colleen M. Sitlani, Raymond Noordam, James D Stewart, Stephanie M Gogarten, Kerri L Wiggins, Stella Trompet, Helen R Warren, Fangui SunAbstract:Background Increased heart rate and a prolonged QT interval are important risk factors for cardiovascular morbidity and mortality, and can be influenced by the use of various medications, including tricyclic/Tetracyclic Antidepressants (TCAs). We aim to identify genetic loci that modify the association between TCA use and RR and QT intervals. Methods and results We conducted race/ethnic-specific genome-wide interaction analyses (with HapMap phase II imputed reference panel imputation) of TCAs and resting RR and QT intervals in cohorts of European (n=45 706; n=1417 TCA users), African (n=10 235; n=296 TCA users) and Hispanic/Latino (n=13 808; n=147 TCA users) ancestry, adjusted for clinical covariates. Among the populations of European ancestry, two genome-wide significant loci were identified for RR interval: rs6737205 in BRE (β=56.3, p interaction =3.9e −9 ) and rs9830388 in UBE2E2 (β=25.2, p interaction =1.7e −8 ). In Hispanic/Latino cohorts, rs2291477 in TGFBR3 significantly modified the association between TCAs and QT intervals (β=9.3, p interaction =2.55e −8 ). In the meta-analyses of the other ethnicities, these loci either were excluded from the meta-analyses (as part of quality control), or their effects did not reach the level of nominal statistical significance (p interaction >0.05). No new variants were identified in these ethnicities. No additional loci were identified after inverse-variance-weighted meta-analysis of the three ancestries. Conclusions Among Europeans, TCA interactions with variants in BRE and UBE2E2 were identified in relation to RR intervals. Among Hispanic/Latinos, variants in TGFBR3 modified the relation between TCAs and QT intervals. Future studies are required to confirm our results.
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Drug–gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval
The Pharmacogenomics Journal, 2014Co-Authors: Christy L. Avery, Colleen M. Sitlani, Dan E. Arking, Donna K. Arnett, Joshua C. Bis, Eric Boerwinkle, Brendan M. Buckley, A.j.m. De Craen, Y-d Ida Chen, Mark EijgelsheimAbstract:Variability in response to drug use is common and heritable, suggesting that genome-wide pharmacogenomics studies may help explain the ‘missing heritability’ of complex traits. Here, we describe four independent analyses in 33 781 participants of European ancestry from 10 cohorts that were designed to identify genetic variants modifying the effects of drugs on QT interval duration (QT). Each analysis cross-sectionally examined four therapeutic classes: thiazide diuretics (prevalence of use=13.0%), tri/Tetracyclic Antidepressants (2.6%), sulfonylurea hypoglycemic agents (2.9%) and QT-prolonging drugs as classified by the University of Arizona Center for Education and Research on Therapeutics (4.4%). Drug–gene interactions were estimated using covariable-adjusted linear regression and results were combined with fixed-effects meta-analysis. Although drug–single-nucleotide polymorphism (SNP) interactions were biologically plausible and variables were well-measured, findings from the four cross-sectional meta-analyses were null ( P _interaction>5.0 × 10^−8). Simulations suggested that additional efforts, including longitudinal modeling to increase statistical power, are likely needed to identify potentially important pharmacogenomic effects.
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Drug-gene interactions and the search for missing heritability: A cross-sectional pharmacogenomics study of the QT interval
'Springer Science and Business Media LLC', 2014Co-Authors: Cl Avery, Colleen M. Sitlani, Dan E. Arking, Joshua C. Bis, Y.-d. Ida Chen, Boerwinkle E, Dk Arnett, Bm Buckley, De Craen Ajm, Eijgelsheim MAbstract:Variability in response to drug use is common and heritable, suggesting that genome-wide pharmacogenomics studies may help explain the 'missing heritability' of complex traits. Here, we describe four independent analyses in 33 781 participants of European ancestry from 10 cohorts that were designed to identify genetic variants modifying the effects of drugs on QT interval duration (QT). Each analysis cross-sectionally examined four therapeutic classes: thiazide diuretics (prevalence of use=13.0%), tri/Tetracyclic Antidepressants (2.6%), sulfonylurea hypoglycemic agents (2.9%) and QT-prolonging drugs as classified by the University of Arizona Center for Education and Research on Therapeutics (4.4%). Drug-gene interactions were estimated using covariable-adjusted linear regression and results were combined with fixed-effects meta-analysis. Although drug-single-nucleotide polymorphism (SNP) interactions were biologically plausible and variables were well-measured, findings from the four cross-sectional meta-analyses were null (P interaction >5.0 × 10 -8). Simulations suggested that additional efforts, including longitudinal modeling to increase statistical power, are likely needed to identify potentially important pharmacogenomic effects. © 2014 Macmillan Publishers Limited All rights reserved
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Drug-gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval.
The pharmacogenomics journal, 2013Co-Authors: Christy L. Avery, Colleen M. Sitlani, Dan E. Arking, Donna K. Arnett, Joshua C. Bis, Eric Boerwinkle, Brendan M. Buckley, Y.-d. Ida Chen, A.j.m. De Craen, Mark EijgelsheimAbstract:Variability in response to drug use is common and heritable, suggesting that genome-wide pharmacogenomics studies may help explain the 'missing heritability' of complex traits. Here, we describe four independent analyses in 33 781 participants of European ancestry from 10 cohorts that were designed to identify genetic variants modifying the effects of drugs on QT interval duration (QT). Each analysis cross-sectionally examined four therapeutic classes: thiazide diuretics (prevalence of use=13.0%), tri/Tetracyclic Antidepressants (2.6%), sulfonylurea hypoglycemic agents (2.9%) and QT-prolonging drugs as classified by the University of Arizona Center for Education and Research on Therapeutics (4.4%). Drug-gene interactions were estimated using covariable-adjusted linear regression and results were combined with fixed-effects meta-analysis. Although drug-single-nucleotide polymorphism (SNP) interactions were biologically plausible and variables were well-measured, findings from the four cross-sectional meta-analyses were null (Pinteraction>5.0 × 10(-8)). Simulations suggested that additional efforts, including longitudinal modeling to increase statistical power, are likely needed to identify potentially important pharmacogenomic effects.
Mark Eijgelsheim - One of the best experts on this subject based on the ideXlab platform.
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Drug–gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval
The Pharmacogenomics Journal, 2014Co-Authors: Christy L. Avery, Colleen M. Sitlani, Dan E. Arking, Donna K. Arnett, Joshua C. Bis, Eric Boerwinkle, Brendan M. Buckley, A.j.m. De Craen, Y-d Ida Chen, Mark EijgelsheimAbstract:Variability in response to drug use is common and heritable, suggesting that genome-wide pharmacogenomics studies may help explain the ‘missing heritability’ of complex traits. Here, we describe four independent analyses in 33 781 participants of European ancestry from 10 cohorts that were designed to identify genetic variants modifying the effects of drugs on QT interval duration (QT). Each analysis cross-sectionally examined four therapeutic classes: thiazide diuretics (prevalence of use=13.0%), tri/Tetracyclic Antidepressants (2.6%), sulfonylurea hypoglycemic agents (2.9%) and QT-prolonging drugs as classified by the University of Arizona Center for Education and Research on Therapeutics (4.4%). Drug–gene interactions were estimated using covariable-adjusted linear regression and results were combined with fixed-effects meta-analysis. Although drug–single-nucleotide polymorphism (SNP) interactions were biologically plausible and variables were well-measured, findings from the four cross-sectional meta-analyses were null ( P _interaction>5.0 × 10^−8). Simulations suggested that additional efforts, including longitudinal modeling to increase statistical power, are likely needed to identify potentially important pharmacogenomic effects.
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Drug-gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval.
The pharmacogenomics journal, 2013Co-Authors: Christy L. Avery, Colleen M. Sitlani, Dan E. Arking, Donna K. Arnett, Joshua C. Bis, Eric Boerwinkle, Brendan M. Buckley, Y.-d. Ida Chen, A.j.m. De Craen, Mark EijgelsheimAbstract:Variability in response to drug use is common and heritable, suggesting that genome-wide pharmacogenomics studies may help explain the 'missing heritability' of complex traits. Here, we describe four independent analyses in 33 781 participants of European ancestry from 10 cohorts that were designed to identify genetic variants modifying the effects of drugs on QT interval duration (QT). Each analysis cross-sectionally examined four therapeutic classes: thiazide diuretics (prevalence of use=13.0%), tri/Tetracyclic Antidepressants (2.6%), sulfonylurea hypoglycemic agents (2.9%) and QT-prolonging drugs as classified by the University of Arizona Center for Education and Research on Therapeutics (4.4%). Drug-gene interactions were estimated using covariable-adjusted linear regression and results were combined with fixed-effects meta-analysis. Although drug-single-nucleotide polymorphism (SNP) interactions were biologically plausible and variables were well-measured, findings from the four cross-sectional meta-analyses were null (Pinteraction>5.0 × 10(-8)). Simulations suggested that additional efforts, including longitudinal modeling to increase statistical power, are likely needed to identify potentially important pharmacogenomic effects.
Raymond Noordam - One of the best experts on this subject based on the ideXlab platform.
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a genome wide interaction analysis of tricyclic Tetracyclic Antidepressants and rr and qt intervals a pharmacogenomics study from the cohorts for heart and aging research in genomic epidemiology charge consortium
Journal of Medical Genetics, 2017Co-Authors: Christy L. Avery, Colleen M. Sitlani, Raymond Noordam, James D Stewart, Stephanie M Gogarten, Kerri L Wiggins, Stella Trompet, Helen R Warren, Fangui SunAbstract:Background Increased heart rate and a prolonged QT interval are important risk factors for cardiovascular morbidity and mortality, and can be influenced by the use of various medications, including tricyclic/Tetracyclic Antidepressants (TCAs). We aim to identify genetic loci that modify the association between TCA use and RR and QT intervals. Methods and results We conducted race/ethnic-specific genome-wide interaction analyses (with HapMap phase II imputed reference panel imputation) of TCAs and resting RR and QT intervals in cohorts of European (n=45 706; n=1417 TCA users), African (n=10 235; n=296 TCA users) and Hispanic/Latino (n=13 808; n=147 TCA users) ancestry, adjusted for clinical covariates. Among the populations of European ancestry, two genome-wide significant loci were identified for RR interval: rs6737205 in BRE (β=56.3, p interaction =3.9e −9 ) and rs9830388 in UBE2E2 (β=25.2, p interaction =1.7e −8 ). In Hispanic/Latino cohorts, rs2291477 in TGFBR3 significantly modified the association between TCAs and QT intervals (β=9.3, p interaction =2.55e −8 ). In the meta-analyses of the other ethnicities, these loci either were excluded from the meta-analyses (as part of quality control), or their effects did not reach the level of nominal statistical significance (p interaction >0.05). No new variants were identified in these ethnicities. No additional loci were identified after inverse-variance-weighted meta-analysis of the three ancestries. Conclusions Among Europeans, TCA interactions with variants in BRE and UBE2E2 were identified in relation to RR intervals. Among Hispanic/Latinos, variants in TGFBR3 modified the relation between TCAs and QT intervals. Future studies are required to confirm our results.
Andres Ricardo Perez Riera - One of the best experts on this subject based on the ideXlab platform.
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brugada syndrome report of the second consensus conference
Heart Rhythm, 2005Co-Authors: Charles Antzelevitch, Pedro Brugada, Martin Borggrefe, Josep Brugada, Ramon Brugada, Domenico Corrado, Ihor Gussak, Herve Lemarec, Koonlawee Nademanee, Andres Ricardo Perez RieraAbstract:Since its introduction as a clinical entity in 1992, the Brugada syndrome has progressed from being a rare disease to one that is second only to automobile accidents as a cause of death among young adults in some countries. Electrocardiographically characterized by a distinct ST-segment elevation in the right precordial leads, the syndrome is associated with a high risk for sudden cardiac death in young and otherwise healthy adults, and less frequently in infants and children. Patients with a spontaneously appearing Brugada ECG have a high risk for sudden arrhythmic death secondary to ventricular tachycardia/fibrillation. The ECG manifestations of Brugada syndrome are often dynamic or concealed and may be unmasked or modulated by sodium channel blockers, a febrile state, vagotonic agents, alpha-adrenergic agonists, beta-adrenergic blockers, tricyclic or Tetracyclic Antidepressants, a combination of glucose and insulin, hypo- and hyperkalemia, hypercalcemia, and alcohol and cocaine toxicity. In recent years, an exponential rise in the number of reported cases and a striking proliferation of articles defining the clinical, genetic, cellular, ionic, and molecular aspects of the disease have occurred. The report of the first consensus conference, published in 2002, focused on diagnostic criteria. The present report, which emanated from the second consensus conference held in September 2003, elaborates further on the diagnostic criteria and examines risk stratification schemes and device and pharmacological approaches to therapy on the basis of the available clinical and basic science data
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brugada syndrome report of the second consensus conference endorsed by the heart rhythm society and the european heart rhythm association
Circulation, 2005Co-Authors: Charles Antzelevitch, Pedro Brugada, Martin Borggrefe, Josep Brugada, Ramon Brugada, Domenico Corrado, Ihor Gussak, Herve Lemarec, Koonlawee Nademanee, Andres Ricardo Perez RieraAbstract:Since its introduction as a clinical entity in 1992, the Brugada syndrome has progressed from being a rare disease to one that is second only to automobile accidents as a cause of death among young adults in some countries. Electrocardiographically characterized by a distinct ST-segment elevation in the right precordial leads, the syndrome is associated with a high risk for sudden cardiac death in young and otherwise healthy adults, and less frequently in infants and children. Patients with a spontaneously appearing Brugada ECG have a high risk for sudden arrhythmic death secondary to ventricular tachycardia/fibrillation. The ECG manifestations of Brugada syndrome are often dynamic or concealed and may be unmasked or modulated by sodium channel blockers, a febrile state, vagotonic agents, α-adrenergic agonists, β-adrenergic blockers, tricyclic or Tetracyclic Antidepressants, a combination of glucose and insulin, hypo- and hyperkalemia, hypercalcemia, and alcohol and cocaine toxicity. In recent years, an exponential rise in the number of reported cases and a striking proliferation of articles defining the clinical, genetic, cellular, ionic, and molecular aspects of the disease have occurred. The report of the first consensus conference, published in 2002, focused on diagnostic criteria. The present report, which emanated from the second consensus conference held in September 2003, elaborates further on the diagnostic criteria and examines risk stratification schemes and device and pharmacological approaches to therapy on the basis of the available clinical and basic science data.