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Background  Recently, 34 genes had been associated with differential expression relative to blood pressure (BP)/ hypertension (HTN). We hypothesize that some of the genes associated with BP/HTN are also associated with BP response to antihypertensive treatment with thiazide diuretics.    Methods  We assessed these 34 genes for association with differential expression to BP response to thiazide diuretics with RNA sequencing in whole blood samples from 150 hypertensive participants from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) and PEAR-2 studies. PEAR white and PEAR-2 white and black participants ( n  = 50 for each group) were selected based on the upper and lower quartile of BP response to hydrochlorothiazide (HCTZ) and to chlorthalidone.    Results   FOS, DUSP1  and  PPP1R15A  were differentially expressed across all cohorts (meta-analysis  p -value < 2.0 × 10 − 6 ), and responders to HCTZ or chlorthalidone presented up-regulated transcripts. Rs11065987 in chromosome 12, a  trans -eQTL for expression of  FOS ,  PPP1R15A  and other genes, is also associated with BP response to HCTZ in PEAR whites (SBP: β = − 2.1;  p  = 1.7 × 10 − 3 ; DBP: β = − 1.4;  p  = 2.9 × 10 − 3 ).    Conclusions  These findings suggest  FOS, DUSP1  and  PPP1R15A  as potential molecular determinants of antihypertensive response to thiazide diuretics.    Trial registration   NCT00246519 ,  NCT01203852   www.clinicaltrials.govElectronic supplementary material  The online version of this article (10.1186/s12920-018-0370-x) contains supplementary material, which is available to authorized users.

Blood pressure signature genes and blood pressure response to thiazide diuretics: results from the PEAR and PEAR-2 studies