@article {5978,
	title = {Drug-gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval.},
	journal = {Pharmacogenomics J},
	volume = {14},
	year = {2014},
	month = {2014 Feb},
	pages = {6-13},
	abstract = {<p>Variability in response to drug use is common and heritable, suggesting that genome-wide pharmacogenomics studies may help explain the {\textquoteright}missing heritability{\textquoteright} 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 {\texttimes} 10(-8)). Simulations suggested that additional efforts, including longitudinal modeling to increase statistical power, are likely needed to identify potentially important pharmacogenomic effects.</p>},
	keywords = {Computer Simulation, Cross-Sectional Studies, Drug-Related Side Effects and Adverse Reactions, Electrocardiography, European Continental Ancestry Group, Gene-Environment Interaction, Genome-Wide Association Study, Humans, Linear Models, Long QT Syndrome, Markov Chains, Pharmacogenetics, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable},
	issn = {1473-1150},
	doi = {10.1038/tpj.2013.4},
	author = {Avery, C L and Sitlani, C M and Arking, D E and Arnett, D K and Bis, J C and Boerwinkle, E and Buckley, B M and Ida Chen, Y-D and de Craen, A J M and Eijgelsheim, M and Enquobahrie, D and Evans, D S and Ford, I and Garcia, M E and Gudnason, V and Harris, T B and Heckbert, S R and Hochner, H and Hofman, A and Hsueh, W-C and Isaacs, A and Jukema, J W and Knekt, P and Kors, J A and Krijthe, B P and Kristiansson, K and Laaksonen, M and Liu, Y and Li, X and Macfarlane, P W and Newton-Cheh, C and Nieminen, M S and Oostra, B A and Peloso, G M and Porthan, K and Rice, K and Rivadeneira, F F and Rotter, J I and Salomaa, V and Sattar, N and Siscovick, D S and Slagboom, P E and Smith, A V and Sotoodehnia, N and Stott, D J and Stricker, B H and St{\"u}rmer, T and Trompet, S and Uitterlinden, A G and van Duijn, C and Westendorp, R G J and Witteman, J C and Whitsel, E A and Psaty, B M}
}
