Genetic association of circulating C-reactive protein levels with idiopathic pulmonary fibrosis: a two-sample Mendelian randomization study

Respiratory Research, Год журнала: 2023, Номер 24(1)

Опубликована: Янв. 9, 2023

Several observational studies have found that idiopathic pulmonary fibrosis (IPF) is often accompanied by elevated circulating C-reactive protein (CRP) levels. However, the causal relationship between them remains to be determined. Therefore, our study aimed explore effect of CRP levels on IPF risk two-sample Mendelian randomization (MR) analysis.We analyzed data from two genome-wide association (GWAS) European ancestry, including (204,402 individuals) and (1028 cases 196,986 controls). We primarily used inverse variance weighted (IVW) assess risk. MR-Egger regression MR-PRESSO global test were determine pleiotropy. Heterogeneity was examined with Cochran's Q test. The leave-one-out analysis tested robustness results.We obtained 54 SNPs as instrumental variables (IVs) for levels, these IVs had no significant horizontal pleiotropy, heterogeneity, or bias. MR revealed a increased (ORIVW = 1.446, 95% CI 1.128-1.854, P 0.004).The present indicated could increase developing in people ancestry.

Язык: Английский

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Mendelian randomization study on the causal effects of COVID‐19 on childhood intelligence

Journal of Medical Virology, Год журнала: 2022, Номер 94(7), С. 3233 - 3239

Опубликована: Март 24, 2022

Although individuals with coronavirus disease 2019 (COVID-19) are known to be at increased risk for other conditions resulting from pathogenic changes (including metaplastic or anaplastic) in the lungs and organs organ systems, it is still unknown whether COVID-19 affects childhood intelligence. The present two-sample Mendelian randomization study aims identify genetic causal link between Four instrumental variants (IVs) were chosen largest genome-wide association studies (GWAS) (hospitalized vs. population) (6406 cases 902 088 controls of European ancestry). intelligence GWAS (n = 12 441 ancestry) was used evaluate effect identified COVID-19-associated IVs on We found that as susceptibility increased, followed a decreasing trend, according mr_egger (β -0.156; p 0.601; odds ratio [OR] 0.856; 95% confidence interval [CI]: 0.522-1.405), simple mode -0.126; 0.240; OR 0.882; CI: 0.745-1.044), weighted -0.121; 0.226; 0.886; 0.758-1.036) analyses. This trend further demonstrated by median -0.134; 0.031; 0.875; 0.774-0.988) inverse variance -0.152; 0.004; 0.859; 0.776-0.952). Our analysis suggests genetically decreased Thus, may factor declines

Язык: Английский

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Mendelian Randomization Analyses of Chronic Immune-Mediated Diseases, Circulating Inflammatory Biomarkers, and Cytokines in Relation to Liver Cancer

Cancers, Год журнала: 2023, Номер 15(11), С. 2930 - 2930

Опубликована: Май 26, 2023

Liver cancer is closely linked to chronic inflammation. While observational studies have reported positive associations between extrahepatic immune-mediated diseases and systemic inflammatory biomarkers liver cancer, the genetic association these traits remains elusive merits further investigation. We conducted a two-sample Mendelian randomization (MR) analysis, using as exposures outcome. The summary data of both outcome were retrieved from previous genome-wide (GWAS). Four MR methods, including inverse-variance-weighted (IVW), MR-Egger regression, weighted-median, weighted-mode employed examine cancer. Nine diseases, seven circulating biomarkers, 187 cytokines analyzed in this study. IVW method suggested that none nine associated with risk odds ratios 1.08 (95% CI 0.87-1.35) for asthma, 0.98 0.91-1.06) rheumatoid arthritis, 1.01 0.96-1.07) type 1 diabetes, 0.98-1.03) psoriasis, 0.89-1.08) Crohn's disease, 1.02 0.91-1.13) ulcerative colitis, 0.91 0.74-1.11) celiac 0.93 0.84-1.05) multiple sclerosis, 1.05 0.97-1.13) lupus erythematosus. Similarly, no significant was found after correcting testing. findings consistent across all four methods used Our do not support However, larger-scale GWAS more instruments are needed confirm findings.

Язык: Английский

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Fatty acids and pregnancy-induced hypertension: a Mendelian randomization study

Lipids in Health and Disease, Год журнала: 2023, Номер 22(1)

Опубликована: Авг. 16, 2023

Abstract Background It is well known that pregnancy-induced hypertension (PIH) contributes significantly to the mortality rates of both mothers and babies during pregnancy. The relationship between fatty acids (FAs) PIH remains debatable, with causality two yet be definitively established. Methods Two-sample univariable multivariable Mendelian Randomization (MR) analyses were executed, based on pooled data from Genome-Wide Association Studies (GWAS), investigate any causal impact FAs PIH. A suite methods was employed assess causality, including inverse variance weighting (IVW), weighted median, MR Egger, simple mode, mode. Subsequently, underwent a sensitivity analysis (using Leave-One-Out analysis), heterogeneity test (with MR-PRESSO Cochran’s Q test), as multiple validity MR-Egger regression). In analyses, first grouped observe effect individual factors such diabetes, high blood pressure, body mass index (BMI) incorporated into examination each FA During this process, IVW, MR-Lasso, employed. Results systematic investigation conducted findings indicated Polyunsaturated Fatty Acids (PUFA), Omega3, ratio Omega6 Docosahexaenoic Acid (DHA) have Increases in PUFA, DHA could potentially reduce risk PIH, while an increase Omega6/Omega3 heighten risk. impacts other (including Total Acids, Monounsaturated (MUFA), Saturated (SFA), Omega 6) not substantiated by analysis. univariate leave-one-out analysis, rs174564 identified having significant role. tests found results influenced pleiotropy heterogeneity. After adjusting for BMI, Diabetes Mellitus, pre-existing mirrored those obtained univariable. Conclusion research implies elevated levels circulating DHA, Omega3 may serve protective mechanism against higher ratios These inform clinical strategies prevention.

Язык: Английский

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Mendelian randomization study on causal association of IL-6 signaling with pulmonary arterial hypertension

Clinical and Experimental Hypertension, Год журнала: 2023, Номер 45(1)

Опубликована: Март 5, 2023

A recent Mendelian randomization (MR) did not support an effect of the lead interleukin-6 receptor (IL-6 R) variant on risk pulmonary arterial hypertension (PAH). Thus, we used two sets genetic instrumental variants (IVs) and publicly available PAH genome-wide association studies (GWAS) to reassess causal link between IL-6 signaling PAH.Six independent 34 soluble (sIL-6 IVs from MR reports GWAS including 162,962 European individuals were perform this two-sample study.We found that as genetically increased, reduced using IVW (odds ratio [OR] = 0.023, 95% confidence interval [CI]: 0.0013-0.393; p .0093) weighted median (OR 0.033, CI: 0.0024-0.467; .0116). Otherwise, sIL-6 R increased 1.34, 1.16-1.56; .0001), 1.36, 1.10-1.68; .005), MR-Egger 1.43, 1.05-1.94; .03), mode 1.35, CI for OR: 1.12-1.63; .0035).Our analysis suggested PAH. higher levels may be a factor patients with PAH, whereas protective

Язык: Английский

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Causal link between gut microbiome and schizophrenia: a Mendelian randomization study

Psychiatric Genetics, Год журнала: 2024, Номер unknown

Опубликована: Фев. 20, 2024

Objective Some observational studies have shown that gut microbiome is significantly changed in patients with schizophrenia. We aim to identify the genetic causal link between and Methods A two-sample Mendelian randomization (MR) study was used evaluate schizophrenia 28 microbiome-associated instrumental variants chosen from recent MR reports largest genome-wide association (8-Apr-22 release). Results Inverse variance weighted method showed genetically increased Bacteroidales_S24-7 (per SD) resulted risk of (OR = 1.110, 95% CI: [1.012–1.217], P 0.027). Similarly, Prevotellaceae promoted 1.124, [1.030–1.228], 0.009). However, Lachnospiraceae reduced 0.878, [0.785–0.983], 0.023). In addition, also suppressed by Lactobacillaceae [0.776–0.994], 0.040) Verrucomicrobiaceae 0.860, [0.749–0.987], 0.032). Finally, we did not find any significant results other 23 Conclusion Our analysis suggests promotes risk, whereas Lachnospiraceae, Lactobacillaceae, reduces risk. Thus, regulation disturbed intestinal microbiota may represent a new therapeutic strategy for

Язык: Английский

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

Journal of Infection, Год журнала: 2022, Номер 84(5), С. e85 - e86

Опубликована: Янв. 22, 2022

Язык: Английский

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

Cancer Medicine, Год журнала: 2022, Номер 11(12), С. 2397 - 2404

Опубликована: Апрель 5, 2022

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

Язык: Английский

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Mendelian Randomization Indicates a Causal Role for Omega-3 Fatty Acids in Inflammatory Bowel Disease

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(22), С. 14380 - 14380

Опубликована: Ноя. 19, 2022

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal system. Omega-3 (ω3) fatty acids are polyunsaturated (PUFAs) that largely obtained from diet and have been speculated to decrease inflammatory response involved in IBD; however, causality this association has not established. A two-sample Mendelian randomization (MR) was used assess genetic associations between 249 circulating metabolites measured UK Biobank as exposures IBD outcome. The genome-wide study summary level data for metabolite measurements were derived large European ancestry cohorts. We observed ω3 a significant protective with IBD, multiple modes MR evidence replicated three datasets. instrumental variables causal highlighted an intronic SNP, rs174564, FADS2, protein engaged first step alpha-linolenic acid desaturation leading anti-inflammatory EPA thence DHA production. low ratio ω6 be risk factor, particularly Crohn's disease. supplementation may provide responses required attenuate IBD.

Язык: Английский

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Vitamin D and idiopathic pulmonary fibrosis: a two-sample mendelian randomization study

BMC Pulmonary Medicine, Год журнала: 2023, Номер 23(1)

Опубликована: Авг. 23, 2023

A prospective study of multiple small samples found that idiopathic pulmonary fibrosis (IPF) is often accompanied by a deficiency in Vitamin D levels. However, the causal relationship between two remains to be determined. Therefore, our aims investigate effect serum 1,25-hydroxyvitamin (25(OH)D) on risk IPF through two-sample Mendelian randomization (MR) analysis.Through data analysis from European ancestry-based genome-wide association studies (GWAS), including 401,460 individuals for 25(OH)D levels and 1028 IPF, we primarily employed inverse-variance weighted (IVW) assess risk. MR-Egger regression test was used determine pleiotropy, Cochran's Q conducted heterogeneity testing. Leave-one-out examine robustness results.158 SNPs related were as instrumental variables (IVs). The MR analyses revealed no evidence supporting level circulating IPF. IVW method [OR 0.891, 95%CI (0.523-1.518), P = 0.670]; There significant heterogeneity, pleiotropy bias IVs. (MR Egger 0.081; 0.089); (P 0.774).This Study suggests genetically predicted vitamin concentrations general population are not causally

Язык: Английский

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