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.

中文翻译：

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白细胞和血压：孟德尔随机化研究。

背景高血压(BP)是心血管发病率和死亡率的危险因素。虽然血压受肾脏、脉管系统和交感神经系统的功能调节，但最近的实验数据表明免疫细胞可能在高血压中发挥作用。方法我们研究了英国生物银行人群中主要白细胞类型与血压之间的关系，并使用约 750 000 英国生物银行/国际血压全基因组关联研究联盟的孟德尔随机化 (MR) 分析来检查哪些白细胞数量可能与 BP 有因果关系。结果 观察到淋巴细胞、单核细胞和中性粒细胞计数的五分位数与收缩压、舒张压和脉压升高之间呈正相关（例如，第 1 和第 5 个五分位数的调整收缩压平均值±SE：淋巴细胞分别为 140.13±0.08 和 141.62±0.07 mmHg，单核细胞为 139.51±0.08 对 141.84±0.07 毫米汞柱，以及 137.807 和 137.80 毫米汞柱对 137.80 毫米汞柱和 137.96 毫米汞柱对 137.96 毫米汞柱; 所有 P<10-50）。使用 MR 中的 121 个单核苷酸多态性，通过逆方差加权方法实施，我们确定了淋巴细胞计数与收缩压和舒张压之间的潜在因果关系（因果估计：0.69 [95% CI，0.19-1.20] 和 0.56 [95 % CI, 0.23-0.90] mm Hg 每 1 SD 基因升高的淋巴细胞计数，分别），这与观察结果方向一致。这些逆方差加权估计与其他稳健的 MR 方法一致。SH2B3 基因座中 rs3184504 SNP 的排除减弱了一些 MR 分析中的信号幅度。相反方向的 MR 发现 BP 指数对单核细胞、中性粒细胞和嗜酸性粒细胞计数的积极影响的证据，但对淋巴细胞或嗜碱性粒细胞的计数没有影响。随后在与肾功能或静息心率和运动后心率相关的背景下对淋巴细胞计数进行的 MR 检测表明，淋巴细胞计数与尿白蛋白与肌酐比值呈正相关。结论 观察和遗传分析表明，淋巴细胞计数与收缩压和舒张压之间存在一致的、积极的和潜在的因果关系。和嗜酸性粒细胞，但不是淋巴细胞或嗜碱性粒细胞。随后在与肾功能或静息心率和运动后心率相关的背景下对淋巴细胞计数进行的 MR 检测表明，淋巴细胞计数与尿白蛋白与肌酐比值呈正相关。结论 观察和遗传分析表明，淋巴细胞计数与收缩压和舒张压之间存在一致的、积极的和潜在的因果关系。和嗜酸性粒细胞，但不是淋巴细胞或嗜碱性粒细胞。随后在与肾功能或静息心率和运动后心率相关的背景下对淋巴细胞计数进行的 MR 检测表明，淋巴细胞计数与尿白蛋白与肌酐比值呈正相关。结论 观察和遗传分析表明，淋巴细胞计数与收缩压和舒张压之间存在一致的、积极的和潜在的因果关系。