Causal Relationship Between Lung Function and Atrial Fibrillation: A Two Sample Univariable and Multivariable, Bidirectional Mendelian Randomization Study

Zhang, Qiaoyun; Zhang, Xiaoyu; Zhang, Jie; Wang, Biyan; Meng, Xiaoni; Tian, Qiuyue; Zhang, Jinxia; Jiang, Mengyang; Zhang, Yiqiang; Zheng, Deqiang; Wu, Lijuan; Wang, Wei; Wang, Baoguo; Wang, Youxin

doi:10.3389/fcvm.2021.769198

Cited by 8 publications

(7 citation statements)

References 54 publications

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“…43 Horizontal pleiotropy can be biased when SNPs are associated with confounding factors through pathways that do not involve fatty acids. 44 However, our results using MR-Egger, weighted median, and weighted mode methods had less impact on horizontal multiplicity, with results similar to IVW estimates. 45 In addition, the exclusion of SNPs that were highly significantly associated with causative factors of BD had little effect on the estimates.…”

Section: Discussionsupporting

confidence: 63%

Assessment of causal relationships between omega-3 and omega-6 polyunsaturated fatty acids in bipolar disorder: a 2-sample bidirectional mendelian randomization study

Zhang

Lin

et al. 2023

Food Funct.

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Section: Discussionsupporting

confidence: 63%

Assessment of causal relationships between omega-3 and omega-6 polyunsaturated fatty acids in bipolar disorder: a 2-sample bidirectional mendelian randomization study

Zhang

Lin

et al. 2023

Food Funct.

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“…Unsurprisingly, our MR analysis did not draw causal inferences consistent with observational studies, which was similar to our previously published negative results for causal inference of lung function and atrial fibrillation [ 52 ]. First, a possible reason is the heterogeneity adjusting for potential confounders or concomitant and secondary risk factors (e.g., surgery, cancer, lower extremity varices, immobilization, bronchial superinfection or right ventricular failure [ 51 ]).…”

Section: Discussionsupporting

confidence: 88%

Genetic association and causal inference between lung function and venous thromboembolism

Zhang

et al. 2023

Respir Res

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Background Previous studies have indicated that lower lung function is related to a higher risk of venous thromboembolism (VTE). However, causal inferences may be affected by confounders, coheritability or reverse causality. We aimed to explore the causal association between lung function and VTE. Methods Summary data from public genome-wide association studies (GWAS) for lung function and VTE were obtained from published meta-analysis studies and the FinnGen consortium, respectively. Independent genetic variables significantly related to exposure were filtered as proxy instruments. We adopted linkage disequilibrium score regression (LDSC) and two-sample Mendelian randomization (MR) analyses to infer the genetic backgrounds and causal associations between different lung functions and VTE events. Results LDSC showed a genetic correlation between forced expiratory volume in one second (FEV1) and deep vein thrombosis (DVT) (rg = − 0.189, P = 0.005). In univariate MR (UVMR), there was suggestive evidence for causal associations of genetically predicted force vital capacity (FVC) with DVT (odds ratio (OR) 0.774; 95% confidence interval (CI) 0.641–0.934) via forwards analysis and genetically predicted pulmonary embolism (PE) with FVC (OR 0.989; 95% CI 0.979–0.999) via reverse analysis. Multivariate MR (MVMR) analyses of lung function-specific SNPs suggested no significant direct effects of lung function on VTE, and vice versa. Of note is the borderline causal effect of PE on FEV1 (OR 0.921; 95% CI 0.848–1.000). Conclusions Our findings identified a coheritability of FEV1 (significant) and FVC (suggestive) with DVT. There was no convincing causal relationship between lung function and the risk of VTE events. The borderline causal effect of PE on FEV1 and the significant genetic correlation of FEV1 with DVT may have clinical implications for improving the quality of existing prevention and intervention strategies.

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“…Vertical pleiotropy will occur if a variant shows direct correlations to exposure on the same biological pathway as well as another phenotype, which cannot result in a violation of the IV assumption and can provide a unique causal pathway from genetic variation to outcomes through exposure [ 37 ]. Horizontal pleiotropy can produce bias when SNPs presented associations with confounders via pathways that did not involve omega-3 fatty acids [ 38 ]. Nevertheless, our results from MR-Egger, weighted median, and weighted mode approaches with less effect on horizontal pleiotropy showed similarity to IVW estimates [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

[Retracted] Mendelian Randomization Study of Causal Relationship between Omega‐3 Fatty Acids and Risk of Lung Cancer

Liu

Peng

Tao

et al. 2022

BioMed Research International

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Objective. Evidence suggests that omega-3 fatty acid intake exerts a protective effect on lung cancer, but its causal association with risk of lung cancer remains uncertain. This study attempts to clarify the causal effect of omega-3 fatty acids on lung cancer utilizing genome-wide association study (GWAS) data with Mendelian randomization (MR) approach. Methods. This study acquired omega-3 fatty acid data from the UK Biobank and data of lung cancer patients from the Consortium and International Lung Cancer Consortium (ILCCO). Single-nucleotide polymorphisms (SNPs) associated with omega-3 fatty acids were screened as instrumental variables (IVs) in line with the criteria of p < 5 E − 8 , linkage disequilibrium R 2 > 0.001 and distance < 10000 kb. Through inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode, causal association between omega-3 fatty acids and risk of lung cancer was evaluated. Cochran’s Q test was applied for a heterogeneity test. The pleiotropy and horizontal pleiotropy among IVs were evaluated via MR-Egger regression intercept analysis. Results. Totally, 42 SNPs associated with omega-3 fatty acids were identified as IVs. According to the results of IVW (OR (95% CI): 0.899 (0.817, 0.990), p = 0.03 ), MR-Egger (OR (95% CI): 0.856 (0.750, 0.977), p = 0.026 ), weighted median (OR (95% CI): 0.899 (0.817, 0.990), p = 0.001 ), simple mode (OR (95% CI): 0.901 (-0.678, 1.199), p = 0.478 ), and weighted mode (OR (95% CI): 0.859 (0.782, 0.944), p = 0.003 ), omega-3 fatty acids showed a causal association with low risk of lung cancer. No genetic pleiotropy or horizontal pleiotropy was found according to MR-Egger regression intercept analysis. Conclusion. Our findings provide sufficient evidence that omega-3 fatty acids are causal protective factors of lung cancer. Despite this, further work is required for elucidating the potential mechanisms.

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Causal Relationship Between Lung Function and Atrial Fibrillation: A Two Sample Univariable and Multivariable, Bidirectional Mendelian Randomization Study

Cited by 8 publications

References 54 publications

Assessment of causal relationships between omega-3 and omega-6 polyunsaturated fatty acids in bipolar disorder: a 2-sample bidirectional mendelian randomization study

Assessment of causal relationships between omega-3 and omega-6 polyunsaturated fatty acids in bipolar disorder: a 2-sample bidirectional mendelian randomization study

Genetic association and causal inference between lung function and venous thromboembolism

[Retracted] Mendelian Randomization Study of Causal Relationship between Omega‐3 Fatty Acids and Risk of Lung Cancer

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