Asthma is a chronic, life-threatening disease that affects more than 300 million people worldwide. Dulera (MF/F) is a fixed-dose combination of mometasone furoate (MF), an inhaled corticosteroid (ICS), and formoterol fumarate (F), a long-acting beta agonist (LABA), used in the treatment of persistent asthma. MF has a relatively high affinity for glucocorticoid receptors (GR); therefore, it has the ability to stimulate GR-mediated transactivation of gene expression, including enhancing the expression of anti-inflammatory proteins and decreasing pro-inflammatory protein synthesis [Tan 2008; Umland 2002; Panek 2015]. The primary objective of this genome-wide association study (GWAS) was to evaluate whether there is a genetic predictor associated with loss of asthma control and future risk of severe asthma exacerbation; and if so, evaluate any treatment-related differences. The secondary objective was to identify genetic predictors of differentiated treatment response related to FEV1 and Asthma Disease Activity Score. A total of 943 non-Hispanic whites who provided genetic consent and had valid genotype data were included in this analysis from four similarly designed Dulera (MF/F) Phase III trials (P04073, P04334, P04431, and P04139). The clinical endpoints examined included loss of asthma control, protocol-defined severe asthma exacerbation (SAEx) and its subcomponents, changes in FEV1 or % predicted FEV1 at week 12 or 26, and changes in asthma disease activity score (ADAS-4 or ADAS-6 [Greenberg 2012]) at week 12 or 26. The genetic main effect and the genetic by treatment interaction effect were jointly evaluated. No significant association of genetics with loss of asthma control, SAEx or SAEx subcomponent was found. Rs12189168 in the human GR gene NR3C1 showed genome-wide significance (p-value 1.46x10-9) with changes in FEV1. NR3C1 maps to 5q31, a region genetically linked to asthma. In addition, several SNPs from the gene region CLOCK/PDCL2 (clock circadian regulator / phosducin-like protein 2) reached statistical significance (p-value < 5x10-8) with changes in ADAS-4. The CLOCK gene may be responsible for changes in airway physiology and inflammation associated with marked circadian variability in daily asthma symptoms [Durrington 2014].