Genome-wide association study of white-coat effect in hypertensive patients

Background: White-coat effect (WCE) confounds diagnosis and treatment of hypertension. The prevalence of white-coat hypertension is higher in Europe and Asia compared to other continents suggesting that genetic factors could play a role. Methods: To study genetic variation affecting WCE, we conducted a two-stage genome-wide association study involving 1343 Finnish subjects. For the discovery stage, we used Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (n = 206), providing the mean WCE values from up to four separate office/ambulatory recordings conducted on placebo. Associations with p values <1 × 10^-5 were included in the replication step in three independent cohorts: Haemodynamics in Primary and Secondary Hypertension (DYNAMIC) (n = 182), Finn-Home study (n = 773) and Dietary, Lifestyle and Genetic Determinants of Obesity and Metabolic Syndrome (DILGOM) (n = 182). Results: No single nucleotide polymorphisms reached genome-wide significance for association with either systolic or diastolic WCE. However, two loci provided suggestive evidence for association. A known coronary artery disease risk locus rs2292954 in SPG7 associated with systolic WCE (discovery p value = 2.2 × 10^-6, replication p value = 0.03 in Finn-Home, meta-analysis p value 2.6 × 10^-4), and rs10033652 in RASGEF1B with diastolic WCE (discovery p value = 4.9 × 10^-6, replication p value = 0.04 in DILGOM, meta-analysis p value = 5.0 × 10^-3). Conclusion: This study provides evidence for two novel candidate genes, SPG7 and RASGEF1B, associating with WCE. Our results need to be validated in even larger studies carried out in other populations.