@article {8260,
	title = {Genome-wide meta-analysis of variant-by-diuretic interactions as modulators of lipid traits in persons of European and African ancestry.},
	journal = {Pharmacogenomics J},
	year = {2019},
	month = {2019 Dec 06},
	abstract = {<p>Hypertension (HTN) is a significant risk factor for cardiovascular morbidity and mortality. Metabolic abnormalities, including adverse cholesterol and triglycerides (TG) profiles, are frequent comorbid findings with HTN and contribute to cardiovascular disease. Diuretics, which are used to treat HTN and heart failure, have been associated with worsening of fasting lipid concentrations. Genome-wide meta-analyses with 39,710 European-ancestry (EA) individuals and 9925 African-ancestry (AA) individuals were performed to identify genetic variants that modify the effect of loop or thiazide diuretic use on blood lipid concentrations. Both longitudinal and cross sectional data were used to compute cohort-specific interaction results, which were then combined through meta-analysis in each ancestry. These ancestry-specific results were further combined through trans-ancestry meta-analysis. Analysis of EA data identified two genome-wide significant (p < 5 {\texttimes} 10) loci with single nucleotide variant (SNV)-loop diuretic interaction on TG concentrations (including COL11A1). Analysis of AA data identified one genome-wide significant locus adjacent to BMP2 with SNV-loop diuretic interaction on TG concentrations. Trans-ancestry analysis strengthened evidence of association for SNV-loop diuretic interaction at two loci (KIAA1217 and BAALC). There were few significant SNV-thiazide diuretic interaction associations on TG concentrations and for either diuretic on cholesterol concentrations. Several promising loci were identified that may implicate biologic pathways that contribute to adverse metabolic side effects from diuretic therapy.</p>},
	issn = {1473-1150},
	doi = {10.1038/s41397-019-0132-y},
	author = {de Las Fuentes, L and Sung, Y J and Sitlani, C M and Avery, C L and Bartz, T M and Keyser, C de and Evans, D S and Li, X and Musani, S K and Ruiter, R and Smith, A V and Sun, F and Trompet, S and Xu, H and Arnett, D K and Bis, J C and Broeckel, U and Busch, E L and Chen, Y-D I and Correa, A and Cummings, S R and Floyd, J S and Ford, I and Guo, X and Harris, T B and Ikram, M A and Lange, L and Launer, L J and Reiner, A P and Schwander, K and Smith, N L and Sotoodehnia, N and Stewart, J D and Stott, D J and St{\"u}rmer, T and Taylor, K D and Uitterlinden, A and Vasan, R S and Wiggins, K L and Cupples, L A and Gudnason, V and Heckbert, S R and Jukema, J W and Liu, Y and Psaty, B M and Rao, D C and Rotter, J I and Stricker, B and Wilson, J G and Whitsel, E A}
}
