Elucidating the causal relationship between gut microbiota, metabolites, and diabetic nephropathy in European patients: Revelations from genome-wide bidirectional mendelian randomization analysis

Frontiers in Endocrinology, Год журнала: 2025, Номер 15

Опубликована: Янв. 8, 2025

Previous observational studies suggest a potential link between gut microbiota, metabolites, and diabetic nephropathy. However, the exact causal relationship among these factors remains unclear. We conducted two-sample bidirectional Mendelian randomization study using summary statistics from IEU OpenGWAS Project database to investigate A range of methods, including inverse variance weighting, MR-Egger, weighted median, simple were applied examine associations. Sensitivity analyses performed assess robustness results. Additionally, reverse analysis was conducted, treating significant microbiota as outcome, evaluate effects perform sensitivity testing. This comprehensive approach provided an in-depth assessment interactions The Inverse Variance Weighted estimates revealed that abundance Lachnospiraceae, Parasutterella, Eubacterium exhibited negative on nephropathy, while Coprococcus, Sutterella, Faecalibacterium prausnitzii, Bacteroides vulgatus showed protective against condition. did not identify any associations nephropathy identified microbiota. Furthermore, indicated Cholesterol, Pyridoxate, Hexanoylcarnitine, X-12007, Octanoylcarnitine, 10-nonadecenoate (19:1n9), X-12734, average number double bonds in fatty acid chain had In contrast, Methionine, Glycodeoxycholate, X-06351, 1-stearoylglycerol (1-monostearin), 5-dodecenoate (12:1n7), X-13859, 2-hydroxyglutarate, Glycoproteins, Phospholipids IDL, concentration small HDL particles demonstrated effects. Notably, detect heterogeneity or horizontal pleiotropy, ensuring findings. Modulating diversity composition offers promising strategy for improving incidence prognosis highlights need future clinical trials focusing microbiome-based interventions, potentially utilizing microbiome-dependent metabolites. Such approaches could transform treatment management its associated risk factors, paving way more effective therapeutic strategies combat this debilitating

Язык: Английский

---

COVID-19 infection and longevity: an observational and mendelian randomization study

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Март 6, 2025

Studies have indicated that COVID-19 infection may accelerate the aging process in organisms. However, it remains unknown whether contracting affects life expectancy. Furthermore, underlying biological mechanisms behind these findings are still unclear. We conducted a prospective cohort study on 56,504 participants of European ancestry from UK Biobank who reported time and number between January 2020 September 2023. The parental average longevity was used as proxy for their own longevity. Linear regression to assess relationship we investigated shared genetic basis using large-scale genome-wide association studies (GWAS) (122,616 cases 2,475,240 controls) (3,484 25,483 controls). Mendelian randomization (MR) mediation analysis were utilized causal relationships potential mediators susceptibility Shared loci two phenotypes identified conjunctional false discovery rate (conjFDR) statistical frameworks. After controlling relevant covariates, might not be significantly correlated with In all MR methods, generalized summary-data-based (GSMR) revealed significant decrease due severe (OR = 0.91, 95%CI: 0.84-0.98, P 0.015). Mediation stroke myocardial infarction reduced At conjFDR < 0.05, rs62062323 (KANSL1) rs9530111 (PIBF1) Together, our provided preliminary evidence basics aging. This implications personalized medicine preventive strategies, helping identify individuals more vulnerable outcomes makeup.

Язык: Английский

---

Functional characterization of the SDR42E1 reveals its role in vitamin D biosynthesis

Heliyon, Год журнала: 2024, Номер 10(17), С. e36466 - e36466

Опубликована: Авг. 17, 2024

Vitamin D deficiency poses a widespread health challenge, shaped by environmental and genetic determinants. A recent discovery identified regulator, rs11542462, in the

Язык: Английский

---

Micronutrients, Vitamin D, and Inflammatory Biomarkers in COVID-19: A Systematic Review and Meta-analysis of Causal Inference Studies

Nutrition Reviews, Год журнала: 2024, Номер unknown

Опубликована: Окт. 24, 2024

Abstract Context Experimental and observational studies suggest that circulating micronutrients, including vitamin D (VD), may increase COVID-19 risk its associated outcomes. Mendelian randomization (MR) provide valuable insight into the causal relationship between an exposure disease Objectives The aim was to conduct a systematic review meta-analysis of inference apply MR approaches assess role these particularly VD, in risk, infection severity, related inflammatory markers. Data Sources Searches (up July 2023) were conducted 4 databases. Extraction Analysis quality evaluated based on MR-STROBE guidelines. Random-effects meta-analyses where possible. Results There 28 (2 overlapped) 12 micronutrients (8 VD) COVID-19, (all inflammation, markers COVID-19. Some reported significant associations VD or other (vitamin C, B6, iron, zinc, copper, selenium, magnesium) Associations terms causality also nonsignificant with regard inflammation-related markers, except for levels below 25 nmol/L C-reactive protein (CRP). cytokines, angiotensin-converting enzyme 2 (ACE2), Pooled estimates showed not significantly outcomes, whereas ACE2 increased (MR odds ratio = 1.10; 95% CI: 1.01–1.19) but did affect hospitalization severity disease. methodological high 13 studies, despite majority (n 24) utilizing 2-sample pleiotropy. Conclusion exhibited diversity their do support link VD/micronutrients Whether inflammation mediates VD–COVID-19 remains uncertain, highlights need address this aspect future exploring micronutrient Systematic Review Registration PROSPERO registration no. CRD42022328224.

Язык: Английский

---

Genetic determinants of Vitamin D deficiency in the Middle Eastern Qatari population: a genome-wide association study

Frontiers in Nutrition, Год журнала: 2023, Номер 10

Опубликована: Сен. 29, 2023

Epidemiological studies have consistently revealed that Vitamin D deficiency is most prevalent in Middle Eastern countries. However, research on the impact of genetic loci and polygenic models related to has primarily focused European populations.We conducted first genome-wide association study identify determinants levels Easterners using a whole genome sequencing approach 6,047 subjects from Qatar Biobank (QBB) project. We performed GWAS meta-analysis, combining QBB cohort with recent data UK (involving 345,923 individuals). Additionally, we evaluated performance European-derived risk scores cohort.Our identified an between variant known locus for group-specific component gene (GC), specifically rs2298850 (p-value = 1.71 × 10-08, Beta -0.1285), levels. Furthermore, our meta-analysis two novel variants at chromosome 11, rs67609747 rs1945603, reached significance threshold. Notably, observed moderately high heritability D, estimated 18%, compared Europeans. Despite lower predictive Qataris Europeans, exhibited significant links within cohort.This reveals architecture contributing Qatari population, emphasizing heterogeneity across different populations.

Язык: Английский

---

Mendelian randomization study supports the causal effects of air pollution on longevity via multiple age-related diseases

npj Aging, Год журнала: 2023, Номер 9(1)

Опубликована: Дек. 19, 2023

Growing evidence suggests that exposure to fine particulate matter (PM2.5) may reduce life expectancy; however, the causal pathways of PM2.5 affecting expectancy remain unknown. Here, we assess effects genetically predicted concentration on common chronic diseases and longevity using a Mendelian randomization (MR) statistical framework based large-scale genome-wide association studies (GWAS) (>400,000 participants). After adjusting for other types air pollution smoking, find significant relationships between angina pectoris, hypercholesterolaemia hypothyroidism, but no relationship with longevity. Mediation analysis shows although is not significant, indirectly affects via diastolic blood pressure (DBP), hypertension, Alzheimer's disease, mediated proportion 31.5, 70.9, 2.5, 100, 24.7%, respectively. Our findings indicate public health policies control help improve expectancy.

Язык: Английский

---

Integration of multiple-omics data to reveal the shared genetic architecture of educational attainment, intelligence, cognitive performance, and Alzheimer’s disease

Frontiers in Genetics, Год журнала: 2023, Номер 14

Опубликована: Окт. 12, 2023

Growing evidence suggests the effect of educational attainment (EA) on Alzheimer’s disease (AD), but less is known about shared genetic architecture between them. Here, leveraging genome-wide association studies (GWAS) for AD (N = 21,982/41,944), EA 1,131,881), cognitive performance 257,828), and intelligence 78,308), we investigated their causal with linkage disequilibrium score (LDSC) Mendelian randomization loci conjunctional false discovery rate (conjFDR), transcriptome-wide (TWAS), colocalization. We observed significant correlations (r g −0.22, p 5.07E-05), −0.27, 2.44E-05), −0.30, 3.00E-04) AD, a relationship (OR 0.74, 95% CI: 0.58–0.94, 0.013). identified 13 at conjFDR &lt;0.01, which five were novel, prioritized three genes. These findings inform early prevention strategies AD.

Язык: Английский

---

Genome-wide analysis reveals extensive genetic overlap between childhood phenotypes and later-life type 2 diabetes

Computers in Biology and Medicine, Год журнала: 2024, Номер 171, С. 108065 - 108065

Опубликована: Янв. 29, 2024

Язык: Английский

---

A causal relationship between sleep behaviour and osteoporosis: a two-sample reverse-mediated Mendelian randomisation study

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Апрель 12, 2024

Abstract Background In recent years, there have been more and clinical observational studies on sleep behaviour osteoporosis, but the causal relationship between osteoporosis at genetic level, whether are mediating factors two is still unclear. Methods From published GWAS data, seven behaviours were selected as exposure factors: insomnia, time, getting up in morning, napping during day, type (early/late rise), narcolepsy snoring. Bone mineral density of heel (H-BMD), forearm (FA-BMD), lumbar vertebra (LS-BMD) femoral neck (FN-BMD) outcome factors. The low-density lipoprotein cholesterol (LDL-C) triglyceride (TG) was analyzed through Mendelian randomization. Results results a two-sample randomization study showed that snoring positively correlated with bone (OR = 1.555, 95%CI: 1.189–2.032, P 0.001). reverse not cause (P 0.466). Mediating both LDL triglycerides had effects 0.92, 0.87–0.98, 5.56e-3) 1.17, 1.09–01.26, 3.72e-5). Conclusions Our shows factor affecting density, play an intermediary role it. Therefore, correcting controlling index should be included regimen for preventing treating decline.

Язык: Английский

---

Bidirectional Mendelian randomization explores the causal relationship between arthritis and cerebral cortical volume

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Май 22, 2024

Background Mendelian randomization method was used to explore the causal relationship between occurrence of arthritis disease and volume changes in specific cerebral cortical regions. Methods By analyzing GWAS summary data,SNP data related cortex were selected.Using inverse variance weighted (IVW) as preferred method, MR Egger, Simple Mode, Weighted Median, Mode auxiliary analysis conduct a two-sample bidirectional analysis. Result IVW showed that Arthrosis positively correlated with Left Crus I Cerebellum (OR = 1.18, 95%CI: 1.09 ~ 1.28, P 9×10^{− 5}).Gout negatively Frontal Operculum Cortex 0.97, 95% CI: 0.95 0.98, 5×10^{− Precentral Gyrus 1.05, 1.04 1.07, 1.9×10− 11).No positive results obtained by reverse Conclusion promotes increased Cerebellum.Gout decreased Cortex.Gout Gyrus.}

Язык: Английский

---