The Association between Non-Alcohol Liver Fatty Disease and Coronary Artery Calcification: A Two-Sample Mendelian Randomization Study.

IF 8.4 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS European journal of preventive cardiology Pub Date : 2024-10-14 DOI:10.1093/eurjpc/zwae336
Liaoming He, Xieraili Tiemuerniyazi, Ziang Yang, Shengkang Huang, Lianxin Chen, Yifeng Nan, Yangwu Song, Wei Feng
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Abstract

Background: Although prior observational studies have suggested that patients with non-alcohol fatty liver disease (NAFLD) may have a higher risk of coronary artery calcification (CAC), these findings remain controversial. This study aimed to explore the causal association between NAFLD and CAC at genetic level by two-sample Mendelian randomization (MR) analysis.

Method: Utilizing summary-level data from multiple large-scale genome-wide association studies (GWAS) in European populations, a two-sample MR analysis was initially conducted to explore the potential causal association between NAFLD and CAC. The results of the MR analysis were pooled through random-effect meta-analysis. The inverse variance weighting (IVW) method served as the primary approach for MR analysis. Additionally, the weighted median, MR-Egger and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods was applied for sensitivity analysis. Summary-level data on liver fatty content was utilized for validation analysis, while summary-level data on cirrhosis served as positive control, further ensuring the validity and robustness of our findings. Reverse MR analysis was performed to assess the association between CAC and NAFLD, employing instrument variables derived from CAC.

Results: The MR analysis indicated that genetically predicted NAFLD had no effects on the risk of CAC (Beta: 0.01, 95% CI: -0.02 to 0.03, P = 0.74). Likewise, the reverse MR analysis found no significant genetic association between CAC and NAFLD (OR: 1.00, 95% CI: 0.96 to 1.06, P = 0.88). Validation analysis yielded consistent results, showing no significant association between fatty liver content and CAC.

Conclusion: Our two-sample MR analysis did not support that there is a causal association between NAFLD and CAC at genetic level. The association between NAFLD and CAC reported in some previous observational studies may rely on NAFLD complicated with metabolic disorders, rather than being directly linked to the hepatic steatosis.

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非酒精性肝脂肪疾病与冠状动脉钙化之间的关系:双样本孟德尔随机研究
背景:尽管之前的观察性研究表明,非酒精性脂肪肝(NAFLD)患者可能具有较高的冠状动脉钙化(CAC)风险,但这些研究结果仍存在争议。本研究旨在通过双样本孟德尔随机化(MR)分析探讨非酒精性脂肪肝与冠状动脉钙化之间在基因水平上的因果关系:利用欧洲人群中多个大规模全基因组关联研究(GWAS)的汇总数据,首先进行了双样本 MR 分析,以探讨非酒精性脂肪肝与 CAC 之间的潜在因果关系。MR 分析的结果通过随机效应荟萃分析进行了汇总。反方差加权(IVW)法是MR分析的主要方法。此外,加权中值法、MR-Egger 法和 MR-pleiotropy 残差和离群值法(MR-PRESSO)也被用于敏感性分析。肝脏脂肪含量的汇总数据用于验证分析,肝硬化的汇总数据作为阳性对照,进一步确保了我们研究结果的有效性和稳健性。我们利用从 CAC 衍生出的工具变量进行了反向 MR 分析,以评估 CAC 与非酒精性脂肪肝之间的关联:MR分析表明,遗传预测的非酒精性脂肪肝对CAC风险没有影响(Beta:0.01,95% CI:-0.02 至 0.03,P = 0.74)。同样,反向 MR 分析也发现 CAC 与非酒精性脂肪肝之间没有明显的遗传关联(OR:1.00,95% CI:0.96 至 1.06,P = 0.88)。验证分析结果一致,显示脂肪肝含量与CAC之间没有明显关联:我们的双样本 MR 分析并不支持非酒精性脂肪肝与 CAC 之间在基因水平上存在因果关系。以往一些观察性研究中报道的非酒精性脂肪肝与 CAC 之间的关联可能依赖于非酒精性脂肪肝并发代谢紊乱,而非与肝脏脂肪变性直接相关。
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来源期刊
European journal of preventive cardiology
European journal of preventive cardiology CARDIAC & CARDIOVASCULAR SYSTEMS-
CiteScore
12.50
自引率
12.00%
发文量
601
审稿时长
3-8 weeks
期刊介绍: European Journal of Preventive Cardiology (EJPC) is an official journal of the European Society of Cardiology (ESC) and the European Association of Preventive Cardiology (EAPC). The journal covers a wide range of scientific, clinical, and public health disciplines related to cardiovascular disease prevention, risk factor management, cardiovascular rehabilitation, population science and public health, and exercise physiology. The categories covered by the journal include classical risk factors and treatment, lifestyle risk factors, non-modifiable cardiovascular risk factors, cardiovascular conditions, concomitant pathological conditions, sport cardiology, diagnostic tests, care settings, epidemiology, pharmacology and pharmacotherapy, machine learning, and artificial intelligence.
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