Physical activity reduces the effect of adiposity genetic liability on hypertension risk in the UK Biobank cohort

Background and Purpose: Hypertension is a leading risk factor for cardiovascular disease (CVD) and is modulated by genetic variants. This study aimed to assess the effect of gene and environmental interaction focusing on adiposity genetic liability and physical activity on hypertension among European and African ancestry individuals within the UK Biobank (UKB). Methods: Participants were 230,115 individuals of European ancestry and 3,239 individuals of African ancestry from UKB. Genetic liability for adiposity were estimated using previously published data including the list of genetic variants and effect sizes for body mass index (BMI), waist-hip ratio (WHR) and waist circumference (WC) using Plink software. The outcome was defined as stage 2 hypertension (systolic blood pressure ? 140 mmHg, diastolic blood pressure ? 90 mmHg, or the use of anti-hypertensive medications). The association between adiposity genetic liability and the outcome was assessed across categories of self-reported physical activity using logistic regression. Results: Among European ancestry participants, there was up to a 20% hypertension risk difference between participants with a combination of high genetic liability and low physical activity compared with participants with a combination of low genetic liability and high physical activity (P <0.001). There was an interaction effect of physical activity on the association between BMI genetic liability and hypertension (P interaction=0.04). There was no evidence of an association between adiposity genetic liability and hypertension in individuals of African ancestry (P > 0.05). Conclusion: This study suggests that engaging in physical activity may reduce the risk of stage 2 hypertension among European ancestry individuals who carry high genetic liability for adiposity. This cannot be inferred for individuals of African ancestry, possibly due to the low African ancestry sample size within the UKB. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement R.P. holds a fellowship supported by Rutherford Fund from Medical Research Council (MR/R026505/1 and MR/R026505/2). UKB genotyping was supported by the British Heart Foundation (grant SP/13/2/30111) for Large-scale comprehensive genotyping of UKB for cardiometabolic traits and diseases: UK CardioMetabolic Consortium. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (or Ethics Committee) of Brunel University London, College of Health, Medicine and Life Sciences (27684-LR-Jan/2021- 29901-1). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Not applicable