Dataset Information

Mendelian Randomization Study of Causal Relationship between Omega-3 Fatty Acids and Risk of Lung Cancer.

ABSTRACT:

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 < 5E - 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.

SUBMITTER: Liu X

PROVIDER: S-EPMC9173898 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mendelian Randomization Study of Causal Relationship between Omega-3 Fatty Acids and Risk of Lung Cancer.

Liu Xin X Peng Yanzhi Y Tao Ru R Meng Ling L Li Xuehua X

BioMed research international 20220531

<h4>Objective</h4>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.<h4>Methods</h4>This study acquired omega-3 fatty acid data from the UK Biobank and data of lung cancer patients from the Consortium and ...[more]

PMID: 35686230

Similar Datasets

Project description:BackgroundOmega-3 and omega-6 may be protective factors for cholelithiasis. However, this relationship has not yet been demonstrated clearly. Therefore, we attempted to identify these causal relationships.Materials and methodsThe omega-3/6 fatty acid discovery dataset was obtained from UK Biobank and contained 114,999 individuals. The validation set was derived from an independent genome-wide association study (GWAS) and contained 13,544 individuals. The cholelithiasis dataset was derived from FinnGen and contained 19,023 cases and 195,144 controls. The inverse variance weighting (IVW) method was used as the main method of analysis in this study. Multiple methods of analysis were also used in the repeated methods, including the MR-Egger, weighted median, MR-pleiotropic residual sum (MR-PRESSO), outliers, and maximum likelihood methods. In addition, we used multiple sensitivity analyses to identify the potential pleiotropy.ResultIn the discovery stage, the results of the random effect IVW analysis showed that higher omega-3 levels were correlated inversely with the risk of cholelithiasis (β = -0.22, 95% CI [-0.32 to -0.12], P = 1.49 × 10-5). When the replication analysis was performed using another set of instrumental variables (IVs), the causal relationship between omega-3 fatty acids and cholelithiasis remained stable (β = -0.42, 95% CI [-0.66 to -0.18], P = 5.49 × 10-4), except for the results obtained using the MR-Egger method, which were not significant. The results of the IVW approach showed that each SD increase in omega-6 levels was associated negatively with the risk of cholelithiasis, both in the discovery (β = -0.21, 95% CI [-0.35 to -0.06], P = 4.37 × 10-3) and the validation phases (β = -0.21, 95% CI [-0.40 to -0.02], P = 3.44 × 10-2).ConclusionThe results of our MR study suggest that omega-3/6 is associated with cholelithiasis risk. Attention to the risk of cholelithiasis in individuals with low serum omega-3/6 levels is necessary.

Project description:BackgroundLung cancer is a highly prevalent neoplastic disease in various regions of the world, but the mechanism of its occurrence, development, and metastasis is not clear. Different hormone levels have different potential roles in the occurrence, development, and metastasis of lung cancer, but the association between hormone levels and lung cancer is not clear.ObjectiveThis study aims to explore the causal relationship between hormone levels and lung cancer using Mendelian randomization. Sensitivity and heterogeneity tests were conducted to ensure the reliability of the results, offering insights into the prevention, diagnosis, and treatment of lung cancer.MethodsWe employed a two-sample Mendelian randomization (MR) analysis using large-scale publicly available genome-wide association studies (GWAS) data to assess the causal relationship between hormone levels and lung cancer. We explored the causal relationship between 15 hormones and three subtypes of lung cancer. The inverse variance weighted (IVW) method was used as the primary analysis, while MR-Egger, weighted median, weighted mode, and simple median were applied as supplementary methods. Sensitivity and heterogeneity tests were conducted to ensure the robustness of the findings.ResultsWe identified six hormone levels to be significantly associated with lung squamous cell carcinoma (LUSC): total testosterone, oestradiol, thyrotropin-releasing hormone, insulin, parathyroid hormone, and glucocorticoid. Among them, total testosterone, estradiol, and thyrotropin-releasing hormone were negatively correlated with morbidity. Insulin, prolactin levels, and parathyroid hormone were positively correlated with morbidity. Five hormone levels were significantly associated with lung adenocarcinoma (LUAD): luteinizing hormone, thyroid hormones, insulin, prolactin levels, and parathyroid hormone. Luteinizing hormone and thyroid hormones were negatively correlated with morbidity, while insulin, prolactin levels, and parathyroid hormone were positively correlated with morbidity. Similarly, five hormone levels were linked to small cell lung cancer (SCLC): total testosterone, luteinizing hormone, estradiol, PTHrP, and insulin. Total testosterone and luteinizing hormone were negatively correlated with morbidity, while estradiol, Parathyroid Hormone-Related Peptide (PTHrP), and insulin were positively correlated with morbidity. Several hormones were associated with different subtypes of lung cancer. Insulin was significantly associated with all three types of lung cancer. Testosterone showed positive effects in LUSC and SCLC, and estradiol had varying effects, with a negative correlation in SCLC and a positive correlation in LUSC. Testosterone and estradiol were not significantly associated with LUAD. Luteinizing hormone showed positive effects in LUAD and SCLC, and parathyroid hormone showed negative effects in LUSC and LUAD.ConclusionThis study demonstrates significant causal relationships between specific hormone levels and various types of lung cancer, providing valuable insights for prevention, diagnosis, and treatment strategies of lung cancer.

Project description:ObjectiveObservational research has indicated a potential link between dietary salt intake and susceptibility to dementia. However, it is important to note that these types of studies are prone to the issues of reverse causation and residual confounding. Therefore, we conducted a two-sample Mendelian randomization (MR) study to explore the causality.MethodTo explore the causal relationship between them, this Mendelian randomization (MR) study incorporated summary statistics of dietary salt intake and dementia. We estimated the causality between salt intake and the risk of overall dementia and various subtypes of dementia, including Alzheimer's disease (AD), Vascular dementia (VaD), and Lewy body dementia (LBD). The inverse variance-weighted (IVW) method was the major MR analysis. To conduct sensitivity analyses, we employed various MR methods, the pleiotropy residual sum and outlier (MR-PRESSO) method, and the leave-one-out approach. The MR-Egger intercept and Cochran's Q test were conducted to test pleiotropy and heterogeneity respectively.ResultsA suggestive association was observed for genetically predicted higher dietary salt intake and increased risk of overall dementia in the European ancestry [odds ratio (OR): 1.542; 95% confidence interval (95% CI): 1.095-2.169; P = 0.013]. The causal relationship between dietary salt intake and overall dementia is robust with respect to the choice of statistical methods and is validated through extensive sensitivity analyses that guard against various model assumption violations. Meanwhile, no clear heterogeneity or pleiotropy was identified. However, we failed to detect a causal effect of dietary salt intake on the risk of various dementia subtypes.ConclusionThe results of this research present strong evidence that established a significant association between dietary salt intake and the likelihood of developing dementia. These findings reinforce the notion that the amount of dietary salt intake plays a crucial role in determining the risk of acquiring this cognitive condition. By establishing a definitive correlation, this study highlights the importance of reducing salt consumption as a preventive measure against dementia.

Project description:IntroductionDespite numerous observational studies reporting a positive correlation between polyunsaturated fatty acids (PUFAs) and the risk of sepsis and mortality, the causation of such an association has yet to be firmly established. Thus, our study aimed to undertake the Mendelian randomization (MR) approach to scrutinize the potential causalities of PUFAs with sepsis and mortality risk.MethodsWe conducted the MR investigation using genome-wide association study (GWAS) summary statistics of PUFAs [including omega-3 fatty acids (omega-3), omega-6 fatty acids (omega-6), the ratio of omega-6 to omega-3 fatty acids (omega-6:3), docosahexaenoic acid (DHA), linoleic acid (LA)], sepsis, and sepsis mortality. We utilized the GWAS summary data from the UK Biobank. To establish reliable causality, we employed the inverse-variance weighted (IVW) method as the primary analytical approach, together with four additional MR methods. In addition, we performed heterogeneity and horizontal pleiotropy assessments using Cochrane's Q test and MR-Egger intercept test, respectively. Finally, we performed a series of sensitivity analyses to enhance the precision and veracity of our findings.ResultsThe IVW method showed that genetically predicted omega-3 [odd ratio (OR) 0.914, 95% confidence interval (CI) 0.845-0.987, P = 0.023] and DHA (OR 0.893, 95% CI 0.815-0.979, P = 0.015) were suggestively linked to a decreased risk of sepsis. Furthermore, genetically predicted DHA (OR 0.819, 95% CI 0.681-0.986, P = 0.035) was suggestively associated with a reduced risk of sepsis-related death. Conversely, the omega-6:3 ratio (OR 1.177, 95% CI 1.011-1.371, P = 0.036) was suggestively linked to an increased risk of sepsis-induced mortality. On the basis of the MR-Egger intercept assessment, it appears that our MR examination was not influenced by any horizontal pleiotropy (all P > 0.05). Moreover, the reliability of the estimated causal association was confirmed by the sensitivity analyses.ConclusionOur study supported the casual effect between PUFAs and susceptibility to sepsis and sepsis-related death. Our findings underline the importance of specific PUFAs levels, particularly for individuals with a genetic susceptibility to sepsis. Further research is needed to confirm these findings and investigate the underlying mechanisms.

Dataset Information

Mendelian Randomization Study of Causal Relationship between Omega-3 Fatty Acids and Risk of Lung Cancer.

Objective

Methods

Results

Conclusion

Publications

Mendelian Randomization Study of Causal Relationship between Omega-3 Fatty Acids and Risk of Lung Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets