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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Abstract
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 |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Maffia, Professor Pasquale and Welsh, Professor Paul and Guzik, Professor Tomasz and Sattar, Professor Naveed and Siedlinski, Mr Mateusz |
| 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 > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
| Journal Name: | Circulation |
| Publisher: | American Heart Association |
| ISSN: | 0009-7322 |
| 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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