White blood cells and blood pressure: a Mendelian randomization study

Siedlinski, M. et al. (2020) White blood cells and blood pressure: a Mendelian randomization study. Circulation, 141(16), pp. 1307-1317. (doi: 10.1161/CIRCULATIONAHA.119.045102) (PMID:32148083) (PMCID:PMC7176352)

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Background: High blood pressure (BP) is a risk factor for cardiovascular morbidity and mortality. While BP is regulated by the function of kidney, vasculature and sympathetic nervous system, recent experimental data suggest that immune cells may play a role in hypertension. Methods: We studied the relationship between major white blood cell types and blood pressure in the UK Biobank population and employed Mendelian randomization (MR) analyses using the ∼750,000 UK-Biobank/International Consortium of Blood Pressure-Genome-Wide Association Studies to examine which leukocyte populations may be causally linked to BP. Results: A positive association between quintiles of lymphocyte, monocyte, neutrophil counts and increased systolic (SBP), diastolic (DBP) and pulse pressure (PP) was observed (e.g. adjusted SBP mean±SE for 1st vs 5th quintile respectively: 140.13±0.08 vs. 141.62±0.07 mmHg for lymphocyte, 139.51±0.08 vs. 141.84±0.07 mmHg for monocyte, and 137.96±0.08 vs. 142.71±0.07 mmHg for neutrophil counts, all p<10-50). Using 121 SNPs in MR implemented through the inverse-variance weighted (IVW) approach, we identified a potential causal relationship of lymphocyte count with SBP and DBP (causal estimates: 0.69 (95%CI: 0.19-1.20) and 0.56 (95%CI: 0.23-0.90) of mmHg per 1 SD genetically elevated lymphocyte count, respectively), which was directionally concordant to the observational findings. These IVW estimates were consistent with other, robust MR methods. Interestingly, the exclusion of rs3184504 SNP in the SH2B3 locus attenuated the magnitude of the signal in some of the MR analyses. MR in the reverse direction found evidence of positive effects of BP indices on counts of monocytes, neutrophils and eosinophils, but not lymphocytes or basophils. Subsequent MR testing of lymphocyte count in the context of genetic correlation with renal function or resting and post-exercise heart rate demonstrated a positive association of lymphocyte count with urinary albumin to creatinine ratio. Conclusions: Observational and genetic analyses demonstrate a concordant, positive and potentially causal relationship of lymphocyte count with SBP and DBP.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Maffia, Professor Pasquale and Sattar, Professor Naveed and Welsh, Dr Paul and Siedlinski, Mr Mateusz and Guzik, Professor Tomasz
Authors: Siedlinski, M., Jozefczuk, E., Xu, X., Teumer, A., Evangelou, E., Schnabel, R. B., Welsh, P., Maffia, P., Erdmann, J., Tomaszewski, M., Caulfield, M. J., Sattar, N., Holmes, M. V., and Guzik, T. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Circulation
Publisher:American Heart Association
ISSN (Online):1524-4539
Published Online:09 March 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Circulation 141(16):1307-1317
Publisher Policy:Reproduced under a Creative Commons License

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