基于肺功能的遗传工具变量与冠心病风险的关联：一项两样本孟德尔随机化研究。

Association of Genetic Instrumental Variables for Lung Function on Coronary Artery Disease Risk: A 2-Sample Mendelian Randomization Study.

机构信息

School of Public Health, University of Hong Kong, Hong Kong Special Administrative Region, China (S.L.A.Y.); and MRC Integrative Epidemiology Unit (M.- C.B., D.A.L.) and Population Health Sciences (M.-C.B., D.A.L.), Bristol Medical School, University of Bristol, United Kingdom.

出版信息

Circ Genom Precis Med. 2018 Apr;11(4):e001952. doi: 10.1161/CIRCGEN.117.001952.

DOI:10.1161/CIRCGEN.117.001952

PMID:29650766

Abstract

BACKGROUND

Lung function, assessed by forced expiratory volume in 1 second (FEV) and forced vital capacity (FVC), is inversely associated with coronary artery disease (CAD), but these associations could be because of confounding or reversed causality. We conducted a 2-sample Mendelian randomization study, using publicly available data from relevant genome-wide association studies, to examine the role of FEV or FVC on CAD.

METHODS

We used the most recent genome-wide association studies on lung function to extract genetic instruments related to FEV and FVC (n=92 749). Data on the association between genetic instruments and CAD were obtained from Coronary Artery Disease Genome wide Replication and Meta-analysis plus The Coronary Artery Disease Genetics 1000 Genomes-based genome-wide association studies (60 801 CAD cases and 123 504 controls). We used inverse-variance weighting with a multiplicative random effect to estimate the genetic instrumented association of FEV and FVC on CAD. Sensitivity analyses included weighted median and MR-Egger methods.

RESULTS

Each SD greater FEV was associated with a lower risk of CAD (odds ratio, 0.78 per SD; 95% confidence interval, 0.62-0.98) with a similar magnitude for FVC on CAD risk (odds ratio, 0.82 per SD; 95% confidence interval, 0.64-1.06). Estimates for FEV were similar when using MR-Egger method (odds ratio, 0.80 per SD; 95% confidence interval, 0.33-1.94) although the magnitude was smaller for weighted median method (odds ratio, 0.93 per SD; 95% confidence interval, 0.75-1.17). Estimates for FVC in the sensitivity analyses were attenuated (median) or changed direction (MR-Egger).

CONCLUSIONS

Our study suggested an inverse relation between FEV and CAD, but for FVC, evidence is less clear.

摘要

背景

第一秒用力呼气量（FEV）和用力肺活量（FVC）评估的肺功能与冠状动脉疾病（CAD）呈负相关，但这些关联可能是由于混杂或反向因果关系所致。我们进行了一项两样本孟德尔随机化研究，使用来自相关全基因组关联研究的公开可用数据，研究 FEV 或 FVC 对 CAD 的作用。

方法

我们使用最新的肺功能全基因组关联研究来提取与 FEV 和 FVC 相关的遗传工具（n=92749）。从冠状动脉疾病全基因组复制和荟萃分析 plus 冠状动脉疾病遗传学 1000 基因组全基因组关联研究中获得遗传工具与 CAD 之间关联的数据（60801 例 CAD 病例和 123504 例对照）。我们使用逆方差加权和乘法随机效应来估计 FEV 和 FVC 对 CAD 的遗传工具关联。敏感性分析包括加权中位数和 MR-Egger 方法。

结果

每个 FEV 的标准差增加与 CAD 风险降低相关（比值比，每标准差 0.78；95%置信区间，0.62-0.98），FVC 对 CAD 风险的影响也相似（比值比，每标准差 0.82；95%置信区间，0.64-1.06）。虽然加权中位数方法的幅度较小（比值比，每标准差 0.93；95%置信区间，0.75-1.17），但使用 MR-Egger 方法时，FEV 的估计值相似（比值比，每标准差 0.80；95%置信区间，0.33-1.94）。敏感性分析中 FVC 的估计值减弱（中位数）或改变方向（MR-Egger）。