Mendelian randomization study on the causal effects of omega-3 fatty acids on rheumatoid arthritis

Zhu, Gaizhi; Zhou, Shi‐Ping; Xu, Yiyao; Gao, Ran; Li, Huan; Zhai, Bing; Liu, Xiaoling; He, Youdi; Wang, Xiaoqian; Han, Gencheng; Su, Wenting; Wang, Renxi

doi:10.1007/s10067-022-06052-y

“…In MR studies, the effect relationship between exposure and outcome is not affected or distorted by confounders and reverse causal associations, which has unique advantages for causal inference of exposure factors [ 24 ]. The mature development of GWAS has laid the foundation for the development of MR research and also has opened a new door for the study of lung cancer risk [ 25 ]. This study adopted large-scale GWAS summary data to explore the causal relationship between omega-3 fatty acids and risk of lung cancer with MR approaches.…”

Section: Discussionmentioning

confidence: 99%

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

Liu

¹

,

Peng

²

,

Tao

³

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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“…All estimates of MR analyses were multiplied by 1.1 and then converted to odds ratio (OR) to quantify the risk of GICs per 10% increase in log‐transformed level of adiponectin. F ‐statistics was used to assess the strength of relationship between instrumental variables and phenotype, and calculated using the following Equation 25 :

F=\frac{R^2/k}{\left(1‐{R}^2\right)/\left(n‐k‐1\right)},

where R 2 is the proportion of adiponectin variance, k is the number of instruments used in the model, and n is the sample size. We used the I 2 ‐GX statistic that calculated from MR‐Egger regression model to estimate the potential relative (dilution) bias due to measurement error 26 .…”

Section: Methodsmentioning

confidence: 99%

Adiponectin and the risk of gastrointestinal cancers in East Asians: Mendelian randomization analysis

Jiang

¹

,

Hu

²

,

Wang

³

et al. 2022

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Background Adiponectin is an important adipocytokine and has been associated with the risks of gastrointestinal cancers (GICs). Mendelian randomization (MR) analysis is needed to assess the causal relationships between adiponectin and GICs. Methods We retrieved the summary data of genome‐wide association studies for adiponectin and six types of GICs in East Asians. A series of quality control steps were performed to select the eligible genetic instrumental tools. Horizontal pleiotropy and between‐SNP heterogeneity were tested to choose the primary MR method. We also conducted sensitivity analyses to test the robustness of the main findings. Results We detected neither heterogeneity nor horizontal pleiotropy for the eligible SNPs in all of the MR analyses. Inverse variance weighted (IVW) was therefore used as the primary method, and suggested that per 10% increase in log‐transformed adiponectin level was significantly associated with a decreased risk of gastric cancer (odds ratio [OR] = 0.88, 95% CI 0.81, 0.96), whereas with an increased risk of hepatocellular carcinoma (OR = 1.26, 95% CI 1.09, 1.44) and of biliary tract cancer (OR = 1.54, 95% CI 1.12, 2.12). However, only the association between adiponectin and HCC risk was statistically significant after correction for multiple testing. No statistically significant association was detected between adiponectin and esophageal (OR = 1.05, 95% CI 0.89, 1.23), pancreatic (OR = 1.04, 95% CI 0.78, 1.37), and colorectal cancers (OR = 1.00, 95% CI 0.93, 1.07). Sensitivity analyses did not find contradictory results. Conclusion High level of adiponectin may have a causal effect on and can serve as a biomarker for the carcinogenesis of gastric cancer, hepatocellular carcinoma, and biliary tract cancer.

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“…3 , 4 MR study has been widely used to assess the causal link between an exposure and an outcome. [3][4][5][6][7] To assess the effect of COVID-19 on endometrial cancer, we performed the present two-sample MR study as followed.First, we extracted genetic instrumental variants (IVs) from COVID-19 GWAS. To date, the largest COVID-19 GWAS was reported by the COVID-19 Host Genetics Initiative in 2020.…”

mentioning

confidence: 99%

“… 3 , 4 MR study has been widely used to assess the causal link between an exposure and an outcome. 3 , 4 , 5 , 6 , 7 To assess the effect of COVID-19 on endometrial cancer, we performed the present two-sample MR study as followed.…”

mentioning

confidence: 99%

Genetic variation associated with COVID-19 is also associated with endometrial cancer

Gao¹,

Xu²,

Zhu³

et al. 2022

Journal of Infection

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Genetic variation associated with COVID-19 is also associated with endometrial cancerDear editor, In this journal, Cai and colleagues described that uterine corpus endometrial carcinoma, esophageal carcinoma, kidney renal papillary cell carcinoma, lung adenocarcinoma, kidney chromophobe, and prostate adenocarcinoma were at the high risk of COVID-19 infection. 1 Recently, in this journal, Qiu and colleagues reported that the high expression of SARS-CoV-2 cell receptors might lead to higher COVID-19 infection rates in cancer patients. 2 However, it is still unclear whether COVID-19 infection is a risk factor for endometrial cancer.Mendelian randomization (MR) study, based on the principle that genetic variants are randomly allocated at meiosis, is independent of many factors that bias observational studies. 3 , 4 MR study has been widely used to assess the causal link between an exposure and an outcome. [3][4][5][6][7] To assess the effect of COVID-19 on endometrial cancer, we performed the present two-sample MR study as followed.First, we extracted genetic instrumental variants (IVs) from COVID-19 GWAS. To date, the largest COVID-19 GWAS was reported by the COVID-19 Host Genetics Initiative in 2020. 8 Primarily, this GWAS is to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic. The summary dataset of COVID-19 GWAS (14,134 cases and 1284,876 controls from European ancestry) is available in https://gwas.mrcieu. ac.uk/datasets/ebi-a-GCST010780 . We selected three independent genome-wide significant variants as COVID-19 genetic IVs using the following criteria 1 : p value ( < 5 × 10 −8 ) on COVID-19; 2 linkage disequilibrium (LD) (r 2 < 0.001) between SNPs 3 ; The F-statistics of all selected IVs (F-statistic > 10) were all above the threshold of weak instruments of F-statistic < 10. 9 The main characteristics of three selected COVID-19 genetic IVs are shown in Suppl. Table 1 .Second, we extracted three selected COVID-19 genetic IVs from endometrial cancer GWAS dataset. To date, the largest endome-

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Mendelian randomization study on the causal effects of omega-3 fatty acids on rheumatoid arthritis

Cited by 36 publications

References 42 publications

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

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

Adiponectin and the risk of gastrointestinal cancers in East Asians: Mendelian randomization analysis

Genetic variation associated with COVID-19 is also associated with endometrial cancer

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