双向孟德尔随机化研究提供的血压对背痛和背痛对 II 型糖尿病的因果效应证据。

Evidence of causal effects of blood pressure on back pain and back pain on type II diabetes provided by a bidirectional Mendelian randomization study.

机构信息

Division of Rehabilitation Care Services, VA Puget Sound Health Care System, 1660 S. Columbian Way, 98108, Seattle, USA; Seattle Epidemiologic Research and Information Center, VA Puget Sound Health Care System, 1660 S. Columbian Way, 98108, Seattle, USA; Department of Rehabilitation Medicine, University of Washington, 325 Ninth Avenue, 98104, Seattle, USA; Clinical Learning, Evidence, and Research (CLEAR) Center, University of Washington, 325 Ninth Avenue, 98104, Seattle, USA.

Department of Natural Sciences, Novosibirsk State University, Pirogova Street 2, 630090,Novosibirsk, Russia; Laboratory of Recombination and Segregation Analysis, Institute of Cytology and Genetics, 630090, Novosibirsk, Russia.

出版信息

Spine J. 2023 Aug;23(8):1161-1171. doi: 10.1016/j.spinee.2023.04.001. Epub 2023 Apr 14.

DOI:10.1016/j.spinee.2023.04.001

Abstract

BACKGROUND CONTEXT

Cardiovascular risk factors (hypertension, dyslipidemia, and type II diabetes) have been proposed as risk factors for back pain. However, few longitudinal studies have found significant associations between cardiovascular risk factors and back pain, and these may be explained by confounding or reverse causation.

PURPOSE

To examine potential causal effects of cardiovascular risk factors on back pain, and vice versa.

STUDY DESIGN

Bidirectional Mendelian randomization (MR) study.

PATIENT SAMPLES

Genome-wide association studies (GWAS) with sample sizes between 173,082 and 1,028,947 participants.

OUTCOME MEASURES

Outcomes included (1) back pain associated with health care use (BP-HC) in the forward MR; and (2) seven cardiovascular phenotypes in the reverse MR, including 2 measurements used for the evaluation of hypertension (diastolic blood pressure and systolic blood pressure), 4 phenotypes related to dyslipidemia (LDL cholesterol, HDL cholesterol, total cholesterol, and triglycerides), and type II diabetes.

METHODS

We used summary statistics from large, publicly available GWAS for BP-HC and the 7 cardiovascular phenotypes to obtain genetic instrumental variables. We examined MR evidence for causal associations using inverse-variance weighted (IVW) analysis, Causal Analysis Using Summary Effect (CAUSE), and sensitivity analyses.

RESULTS

In forward MR analyses of seven cardiovascular phenotypes, diastolic blood pressure was associated with BP-HC across all analyses (IVW estimate: OR = 1.10 per 10.5 mm Hg increase [1.04-1.17], p-value = .001), and significant associations of systolic blood pressure with BP-HC were also found (IVW estimate: OR = 1.09 per 19.3 mm Hg increase [1.04-1.15], p-value = .0006). In reverse MR analyses, only type II diabetes was associated with BP-HC across all analyses (IVW estimate: OR = 1.40 [1.13-1.73], p-value = .002).

CONCLUSIONS

These findings from analyses of large, population-based samples indicate that higher blood pressure increases the risk of BP-HC, and BP-HC itself increases the risk of type II diabetes.

摘要

背景

心血管危险因素（高血压、血脂异常和 2 型糖尿病）已被提出作为腰痛的危险因素。然而，很少有纵向研究发现心血管危险因素与腰痛之间存在显著关联，这些关联可能是由混杂因素或反向因果关系所解释。

目的

研究心血管危险因素对腰痛的潜在因果影响，反之亦然。

研究设计

双向 Mendelian 随机化（MR）研究。

患者样本

全基因组关联研究（GWAS），样本量在 173082 至 1028947 名参与者之间。

结局测量

结局包括（1）前瞻性 MR 中与医疗保健使用相关的腰痛（BP-HC）；以及（2）反向 MR 中的 7 种心血管表型，包括用于评估高血压的 2 项测量（舒张压和收缩压）、4 种与血脂异常相关的表型（LDL 胆固醇、HDL 胆固醇、总胆固醇和甘油三酯）和 2 型糖尿病。

方法

我们使用来自大型、公开可用的 GWAS 中与 BP-HC 和 7 种心血管表型相关的汇总统计数据，获得遗传工具变量。我们使用逆方差加权（IVW）分析、基于汇总效应的因果分析（CAUSE）和敏感性分析来检查因果关联的 MR 证据。

结果

在对 7 种心血管表型的前瞻性 MR 分析中，舒张压在所有分析中均与 BP-HC 相关（IVW 估计值：每增加 10.5mmHg，比值比为 1.10 [1.04-1.17]，p 值=0.001），且收缩压与 BP-HC 之间也存在显著关联（IVW 估计值：每增加 19.3mmHg，比值比为 1.09 [1.04-1.15]，p 值=0.0006）。在反向 MR 分析中，仅 2 型糖尿病在所有分析中与 BP-HC 相关（IVW 估计值：比值比为 1.40 [1.13-1.73]，p 值=0.002）。