{"title":"The Association between Non-Alcohol Liver Fatty Disease and Coronary Artery Calcification: A Two-Sample Mendelian Randomization Study.","authors":"Liaoming He, Xieraili Tiemuerniyazi, Ziang Yang, Shengkang Huang, Lianxin Chen, Yifeng Nan, Yangwu Song, Wei Feng","doi":"10.1093/eurjpc/zwae336","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Method: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":12051,"journal":{"name":"European journal of preventive cardiology","volume":null,"pages":null},"PeriodicalIF":8.4000,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of preventive cardiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/eurjpc/zwae336","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
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.
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.