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White Blood Cells and Blood Pressure: A Mendelian Randomization Study.

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 used 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, and neutrophil counts, and increased systolic BP, diastolic BP, and pulse pressure was observed (eg, adjusted systolic BP mean±SE for 1st versus 5th quintile respectively: 140.13±0.08 versus 141.62±0.07 mm?Hg for lymphocyte, 139.51±0.08 versus 141.84±0.07 mm?Hg for monocyte, and 137.96±0.08 versus 142.71±0.07 mm?Hg for neutrophil counts; all P<10-50). Using 121 single nucleotide polymorphisms in MR, implemented through the inverse-variance weighted approach, we identified a potential causal relationship of lymphocyte count with systolic BP and diastolic BP (causal estimates: 0.69 [95% CI, 0.19-1.20] and 0.56 [95% CI, 0.23-0.90] of mm?Hg per 1 SD genetically elevated lymphocyte count, respectively), which was directionally concordant to the observational findings. These inverse-variance weighted estimates were consistent with other robust MR methods. 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 postexercise heart rate demonstrated a positive association of lymphocyte count with urine albumin-to-creatinine ratio. CONCLUSIONS:Observational and genetic analyses demonstrate a concordant, positive and potentially causal relationship of lymphocyte count with systolic BP and diastolic BP.

SUBMITTER: Siedlinski M

PROVIDER: S-EPMC7176352 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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White Blood Cells and Blood Pressure: A Mendelian Randomization Study.

Siedlinski Mateusz M Jozefczuk Ewelina E Xu Xiaoguang X Teumer Alexander A Evangelou Evangelos E Schnabel Renate B RB Welsh Paul P Maffia Pasquale P Erdmann Jeanette J Tomaszewski Maciej M Caulfield Mark J MJ Sattar Naveed N Holmes Michael V MV Guzik Tomasz J TJ

Circulation 20200309 16

<h4>Background</h4>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.<h4>Methods</h4>We studied the relationship between major white blood cell types and blood pressure in the UK Biobank population and used Mendelian randomization (MR) analyses using the ≈750 000 UK-Biobank/Internationa ...[more]

PMID: 32148083

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Project description:BackgroundPositive associations between the risk of schizophrenia and the level of white blood cells (WBC) count have been suggested by observational studies. However, the causality of this association is still unclear.MethodsWe used a group of bidirectional two-sample Mendelian randomization (MR) analyses to estimate the causal relationship between schizophrenia and WBC count traits (i.e., WBC count, lymphocyte count, neutrophil count, basophil count, eosinophil count, and monocyte count). The threshold of FDR-adjusted P < 0.05 was considered as showing potential evidence of a causal effect. Instrument variables were included based on the genome-wide significance threshold (P < 5 × 10- 8) and linkage disequilibrium (LD) clumping (r2 < 0.01). In total, 81, 95, 85, 87, 76, and 83 schizophrenia-related single nucleotide polymorphisms (SNPs) were used as genetic instruments from Psychiatric Genomics Consortium for six WBC count traits, respectively. And in reverse MR analysis, 458, 206, 408, 468, 473, and 390 variants extracted from six WBC count traits were utilized as genetic instruments, which were obtained from a recent large-scale Genome-Wide Association Study (GWAS).ResultsGenetically predicted schizophrenia was positively associated with the level of WBC count [odds ratio (OR) 1.017, 95% confidence interval (CI) 1.008-1.026; P = 7.53 × 10- 4], basophil count (OR 1.014, 95%CI 1.005-1.022; P = 0.002), eosinophil count (OR 1.021, 95%CI 1.011-1.031; P = 2.77 × 10- 4), monocyte count (OR 1.018, 95%CI 1.009-1.027; P = 4.60 × 10- 4), lymphocyte count (OR 1.021, 95%CI 1.012-1.030; P = 4.51 × 10- 5), and neutrophil count (OR 1.013, 95%CI 1.005-1.022; P = 0.004). WBC count traits are not associated with the risk of schizophrenia in our reverse MR results.ConclusionSchizophrenia is associated with elevated levels of WBC count (i.e., higher WBC count, lymphocyte count, neutrophil count, basophil count, eosinophil count, and monocyte count).

Project description:Objective To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal.Design Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable.Setting CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.Participants Data from 22 studies with 171?213 participants, and an additional 10 published prospective studies with 26?119 participants included in the observational analysis.Main outcome measures The instrumental variable estimation was conducted using the ratio of coefficients approach. Using meta-analysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized.Results Compared with the CC genotype (CC is associated with complete lactase deficiency), the CT/TT genotype (TT is associated with lactose persistence, and CT is associated with certain lactase deficiency) of LCT-13910 (lactase persistence gene) rs4988235 was associated with higher dairy consumption (0.23 (about 55 g/day), 95% confidence interval 0.17 to 0.29) serving/day; P<0.001) and was not associated with systolic blood pressure (0.31, 95% confidence interval -0.05 to 0.68 mm Hg; P=0.09) or risk of hypertension (odds ratio 1.01, 95% confidence interval 0.97 to 1.05; P=0.27). Using LCT-13910 rs4988235 as the instrumental variable, genetically determined dairy consumption was not associated with systolic blood pressure (?=1.35, 95% confidence interval -0.28 to 2.97 mm Hg for each serving/day) or risk of hypertension (odds ratio 1.04, 0.88 to 1.24). Moreover, meta-analysis of the published clinical trials showed that higher dairy intake has no significant effect on change in systolic blood pressure for interventions over one month to 12 months (intervention compared with control groups: ?=-0.21, 95% confidence interval -0.98 to 0.57 mm Hg). In observational analysis, each serving/day increase in dairy consumption was associated with -0.11 (95% confidence interval -0.20 to -0.02 mm Hg; P=0.02) lower systolic blood pressure but not risk of hypertension (odds ratio 0.98, 0.97 to 1.00; P=0.11).Conclusion The weak inverse association between dairy intake and systolic blood pressure in observational studies was not supported by a comprehensive instrumental variable analysis and systematic review of existing clinical trials.

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White Blood Cells and Blood Pressure: A Mendelian Randomization Study.

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White Blood Cells and Blood Pressure: A Mendelian Randomization Study.

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