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Frontiers in Immunology 2024The pathogenesis of vitiligo remains elusive. Emerging evidence suggests that vitiligo is an immune-mediated disorder, in which a plethora of immune cells play pivotal...
BACKGROUND
The pathogenesis of vitiligo remains elusive. Emerging evidence suggests that vitiligo is an immune-mediated disorder, in which a plethora of immune cells play pivotal roles. However, the association between circulating immune cells and vitiligo continues to be enigmatic.
MATERIALS AND METHODS
We extracted single nucleotide polymorphisms (SNPs) associated with immune circulating cells at a genome-wide significance level from the BLOOD CELL CONSORTIUM's genome-wide association study (GWAS) dataset. Summary data for 385,801 cases of vitiligo were obtained from a large-scale Finnish genome-wide association study (ncases=292, ncontrols=385,509). The inverse variance weighted (IVW) method was employed as the primary analytical approach for Mendelian randomization (MR) analysis. Additionally, heterogeneity was assessed using Cochran's Q value, and horizontal pleiotropy was evaluated using MR-Egger Mendelian Randomization Pleiotropy RESidual Sum and Outlier and leave-one-out analyses.
RESULTS
The risk of vitiligo was found to increase with the elevation of 4 circulating immune cells, as evidenced by the odds ratios (ORs) and 95% confidence intervals (CIs): basophils (OR=1.81; 95% CI: 1.01-3.24, p=0.0450), monocytes (OR=1.67; 95% CI: 1.23-2.26, p=0.0009), eosinophils (OR=1.78; 95% CI: 1.22-2.59, p=0.0028), and neutrophils (OR=1.65; 95% CI: 1.08-2.54, p=0.0208). After removing outliers, the sensitivity analysis of the above indicators did not show heterogeneity and pleiotropy.
CONCLUSION
Our findings illuminate the association between circulating immune cells and vitiligo, offering insights that could guide clinical practices in the treatment of vitiligo.
Topics: Vitiligo; Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease
PubMed: 38887286
DOI: 10.3389/fimmu.2024.1391186 -
Causal effects between gut microbiota and endometriosis: a two-sample Mendelian randomisation study.Journal of Obstetrics and Gynaecology :... Dec 2024Previous observational evidence has indicated the potential involvement of the gut microbiota (GM) in the development of endometriosis. However, the causal relationship...
BACKGROUND
Previous observational evidence has indicated the potential involvement of the gut microbiota (GM) in the development of endometriosis. However, the causal relationship of the association remains to be investigated.
METHOD
Genome-wide association study (GWAS) data of GM was obtained from the MiBioGen consortium, and GWAS for endometriosis data was from the FinnGen consortium. Initially, a two-sample Mendelian randomisation (MR) analysis was performed to identify specific bacteria associated with endometriosis. Inverse variance-weighted (IVW) was used as the main MR analysis to infer causal relationships. The other four popular MR methods including MR-Egger regression, weighted mode, weighted median, and simple mode were used for secondary confirmation. Subsequently, these selected bacteria were employed as exposure to investigate their causal effects on six sub-types of endometriosis. Furthermore, reverse MR analysis was implemented to evaluate the reverse causal effects. Cochran's Q statistics was used to test the heterogeneity of instrumental variables (IVs); MR-Egger regression was used to test horizontal pleiotropy; MR-PRESSO and leave-one-out sensitivity analysis were applied to find significant outliers.
RESULT
A total of 1131 single nucleotide polymorphisms (SNPs) were collected as IVs for 196 GM taxa with endometriosis as the outcome. We identified 12 causal relationships between endometriosis and GM taxa including 1 phylum, 3 families, 2 orders, and 6 genera (Rikenellaceae RC9 gut group, Eubacterium ruminantium group, Faecalibacterium, Peptococcus, Clostridium sensu stricto 1, and Ruminococcaceae UCG005). Utilizing the Bonferroni method, we identified phylum Cyanobacteria as the strongest associated GM taxa. Subsequently, 6 significant causal effects were uncovered between the 12 selected specific GM and 6 sub-types of endometriosis. Meanwhile, no reverse causal relationship was found. Further, no horizontal pleiotropy and no significant outliers were detected in the sensitive analysis.
CONCLUSIONS
This MR analysis revealed significant causal effects between GM and endometriosis and phylum Cyanobacteria had the strongest association.
Topics: Endometriosis; Humans; Female; Mendelian Randomization Analysis; Genome-Wide Association Study; Gastrointestinal Microbiome; Polymorphism, Single Nucleotide; Causality
PubMed: 38885114
DOI: 10.1080/01443615.2024.2362415 -
Frontiers in Genetics 2024An association between depression and migraine has been reported in observational studies; however, conventional observational studies are prone to bias. This study aims...
BACKGROUND
An association between depression and migraine has been reported in observational studies; however, conventional observational studies are prone to bias. This study aims to investigate the causal relationship between depression and migraine and to quantify the mediating effects of known risk factors.
METHODS
We applied two-sample Mendelian randomization and utilized single nucleotide polymorphisms as genetic instruments for exposure (depression) and mediators (sleep traits). We utilized summary data on genome-wide association studies for depression, sleep-related traits mediators and migraine. For depression, genome-wide association studies (depression) were utilized as a test cohort for the primary analysis. Moreover, genome-wide association studies (major depressive disorder) were utilized to test the stability of the results for the validation cohort. IVW and MR-Egger regression were applied to test the heterogeneity, and Cochran's Q statistics were calculated to quantitatively evaluate the heterogeneity. MR-PRESSO analyses were utilized to examine and correct possible horizontal pleiotropy through removing outliers, and leave-one-out analyses were utilized to identify outlier SNPs.
RESULTS
Genetically predicted depression was associated with migraine (OR = 1.321, 95% CI: 1.184-1.473, < 0.001). Furthermore, risk factors insomnia was associated with migraine risk (OR = 1.766, 95% CI: 1.120-2.784, = 0.014). The mediator insomnia accounted for 19.5% of the total effect of depression on migraine.
CONCLUSION
These results support a potential causal effect of depression on migraine, partly mediated by insomnia. Therefore, the enhancement of sleep quality and difficulty in falling asleep may reduce the migraine burden occasioned by depression.
PubMed: 38881795
DOI: 10.3389/fgene.2024.1326817 -
The Science of the Total Environment Jun 2024Many of South Africa's current water quality problems have been attributed to diffuse pollution derived from poorly regulated land use/land cover (LULC) transformations....
Many of South Africa's current water quality problems have been attributed to diffuse pollution derived from poorly regulated land use/land cover (LULC) transformations. To mitigate these impacts, the preservation of an adequate amount of natural vegetation within catchment areas is an important management strategy. However, it is not clear how much natural vegetation cover is required to provide adequate levels of protection, nor at which scale(s) this strategy would be most effective. To investigate the possibility of estimating minimum thresholds of natural vegetation required to protect water resources, regression analysis was used to model relationships between water quality (measured using Nemerow's Pollution Index) and metrics of natural vegetation at multiple scales across a sample of sub-catchments located along the western, southern, and south-eastern coast of South Africa. With conspicuous outliers removed, the models were able to explain up to 82 % of the variability in the relationship between land use and water quality. Moreover, a statistically significant, nonlinear, and inverse relationship was found between proportions of natural vegetation cover and pollution levels. This relationship was strongest when measured (1) across the whole catchment and (2) within a 200 m riparian buffer zone. The models further indicated that approximately 80 to 90 % natural vegetation cover was necessary at these scales to maintain water quality at ecologically acceptable levels. Additional nonlinear thresholds estimated using breakpoint analysis suggested that if proportions of natural vegetation fall below 45 % (across the whole catchment) and 60 % (within a 200 m riparian buffer zone) a dramatic increase in pollution levels can be expected. The estimated thresholds are recommended as guidelines that can be used to inform integrated land and water resources management strategies aimed at protecting water quality in the study area. Likewise, the methods described are recommended for the estimation of similar thresholds in other regions.
PubMed: 38880130
DOI: 10.1016/j.scitotenv.2024.173924 -
European Journal of Medical Research Jun 2024Some previous observational studies have linked deep venous thrombosis (DVT) to thyroid diseases; however, the findings were contradictory. This study aimed to...
BACKGROUND
Some previous observational studies have linked deep venous thrombosis (DVT) to thyroid diseases; however, the findings were contradictory. This study aimed to investigate whether some common thyroid diseases can cause DVT using a two-sample Mendelian randomization (MR) approach.
METHODS
This two-sample MR study used single nucleotide polymorphisms (SNPs) identified by the FinnGen genome-wide association studies (GWAS) to be highly associated with some common thyroid diseases, including autoimmune hyperthyroidism (962 cases and 172,976 controls), subacute thyroiditis (418 cases and 187,684 controls), hypothyroidism (26,342 cases and 59,827 controls), and malignant neoplasm of the thyroid gland (989 cases and 217,803 controls. These SNPs were used as instruments. Outcome datasets for the GWAS on DVT (6,767 cases and 330,392 controls) were selected from the UK Biobank data, which was obtained from the Integrative Epidemiology Unit (IEU) open GWAS project. The inverse variance weighted (IVW), MR-Egger and weighted median methods were used to estimate the causal association between DVT and thyroid diseases. The Cochran's Q test was used to quantify the heterogeneity of the instrumental variables (IVs). MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO) was used to detect horizontal pleiotropy. When the causal relationship was significant, bidirectional MR analysis was performed to determine any reverse causal relationships between exposures and outcomes.
RESULTS
This MR study illustrated that autoimmune hyperthyroidism slightly increased the risk of DVT according to the IVW [odds ratio (OR) = 1.0009; p = 0.024] and weighted median methods [OR = 1.001; p = 0.028]. According to Cochran's Q test, there was no evidence of heterogeneity in IVs. Additionally, MR-PRESSO did not detect horizontal pleiotropy (p = 0.972). However, no association was observed between other thyroid diseases and DVT using the IVW, weighted median, and MR-Egger regression methods.
CONCLUSIONS
This study revealed that autoimmune hyperthyroidism may cause DVT; however, more evidence and larger sample sizes are required to draw more precise conclusions.
Topics: Humans; Venous Thrombosis; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Thyroid Diseases; Genetic Predisposition to Disease; Hyperthyroidism
PubMed: 38877527
DOI: 10.1186/s40001-024-01933-1 -
BMC Immunology Jun 2024Previous studies have reported the potential impact of immune cells on kidney stone disease (KSD), but definitive causal relationships have yet to be established. The...
PURPOSE
Previous studies have reported the potential impact of immune cells on kidney stone disease (KSD), but definitive causal relationships have yet to be established. The purpose of this paper is to elucidate the potential causal association between immune cells and KSD by Mendelian randomization (MR) analysis.
METHODS
In our study, a thorough two-sample Mendelian randomization (MR) analysis was performed by us to determine the potential causal relationship between immune cell traits and kidney stone disease. We included a total of four immune traits (median fluorescence intensity (MFI), relative cellular (RC), absolute cellular (AC), and morphological parameters (MP)), which are publicly available data. GWAS summary data related to KSD (9713 cases and 366,693 controls) were obtained from the FinnGen consortium. The primary MR analysis method was Inverse variance weighted. Cochran's Q test, MR Egger, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were used to assess the stability of the results.
RESULTS
After FDR correction, the CD8 on HLA DR + CD8br (OR = 0.95, 95% CI = 0.93-0.98, p-value = 7.20 × 10, q-value = 0.088) was determined to be distinctly associated with KSD, and we also found other 25 suggestive associations between immune cells and KSD, of which 13 associations were suggested as protective factors and 12 associations were suggested as risk factors. There was no horizontal pleiotropy or significant heterogeneity in our MR analysis, as determined by the p-value results of our Cochrane Q-test, MR Egger's intercept test, and MR-PRESSO, which were all > 0.05.
CONCLUSIONS
Our study has explored the potential causal connection between immune cells and KSD by Mendelian randomization analysis, thus providing some insights for future clinical studies.
Topics: Humans; Kidney Calculi; Mendelian Randomization Analysis; Genome-Wide Association Study; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; HLA-DR Antigens
PubMed: 38877395
DOI: 10.1186/s12865-024-00627-x -
The Knee Jun 2024In recent years, coronal lower leg alignment has received significant attention. Two classifications recently described the variability in both femoral and tibial...
BACKGROUND
In recent years, coronal lower leg alignment has received significant attention. Two classifications recently described the variability in both femoral and tibial morphology, resulting in differing native lower limb alignment. The native trochlea and the variability in morphology has received less attention.
METHODS
This is a prospective cohort study of 200 patients undergoing robotically assisted TKA. Preoperative transverse CT scans were used to determine the posterior condylar axis (PCA), transepicondylar axis (TEA), lateral trochlear inclination (LTI), the sulcus angle (SA) and the anterior trochlear line (ATL). Outliers were defined as values > 1.5 IQR from median value. Trochlea dysplasia was defined as LTI < 12°. Gender differences were compared.
RESULTS
In total, 99 patients were female (49.4%). SA had a median of 137.0° (IQR 12°), ATL 4° (IQR 4), LTI 18° (IQR 7°). Median TEA-PCA was 5° external (IQR 3°). There were 5.0% outliers in SA, 3.0% of outliers in ATL, 3.5% outliers in LTI and 4.5% outliers in the TEA-PCA. Trochlear dysplasia was present in 11.5% of the measurements. There was no difference in any of the angles between the genders.
CONCLUSION
The present study demonstrates no difference in trochlea morphology between the genders, rather a significant number of overall outliers in trochlear morphology. Larger cohorts but also, more investigations, are needed to better understand the trochlear morphology of patients undergoing total knee arthroplasty. The personalized alignment strategies and implants need to account for this variability in the population.
PubMed: 38876083
DOI: 10.1016/j.knee.2024.06.002 -
Frontiers in Immunology 2024Extensive research has been conducted on the correlation between adipose tissue and the risk of malignant lymphoma. Despite numerous observational studies exploring this...
BACKGROUND
Extensive research has been conducted on the correlation between adipose tissue and the risk of malignant lymphoma. Despite numerous observational studies exploring this connection, uncertainty remains regarding a causal relationship between adipose tissue and malignant lymphoma.
METHODS
The increase or decrease in adipose tissue was represented by the height of BMI. The BMI and malignant lymphoma genome-wide association studies (GWAS) used a summary dataset from the OPEN GWAS website. Single-nucleotide polymorphisms (SNPs) that met the criteria of P <5e-8 and LD of r= 0.001 in the BMI GWAS were chosen as genetic instrumental variants (IVs). Proxy SNPs with LD of r > 0.8 were identified, while palindromic and outlier SNPs were excluded. Mendelian randomization (MR) analysis used five methods, including inverse-variance weighted (IVW) model, weighted median (WM), MR-Egger, simple mode, and weighted mode. Sensitivity assessments included Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis. Participants randomly selected by the National Center for Health Statistics (NHANSE) and newly diagnosed HL patients at Fujian Medical University Union Hospital were used for external validation.
RESULTS
The results of the MR analysis strongly supported the causal link between BMI and Hodgkin's lymphoma (HL). The research demonstrated that individuals with lower BMI face a significantly increased risk of developing HL, with a 91.65% higher risk (OR = 0.0835, 95% CI 0.0147 - 0.4733, P = 0.005). No signs of horizontal or directional pleiotropy were observed in the MR studies. The validation results aligned with the results from the MR analysis (OR = 0.871, 95% CI 0.826 - 0.918, P< 0.001). And there was no causal relationship between BMI and non-Hodgkin's lymphoma (NHL).
CONCLUSIONS
The MR analysis study demonstrated a direct correlation between lower BMI and HL. This suggested that a decrease in adipose tissue increases the risk of developing HL. Nevertheless, further research is essential to grasp the underlying mechanism of this causal association comprehensively.
Topics: Humans; Mendelian Randomization Analysis; Hodgkin Disease; Adipose Tissue; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Body Mass Index; Genetic Predisposition to Disease; Female; Male; Risk Factors; Adult; Middle Aged
PubMed: 38873599
DOI: 10.3389/fimmu.2024.1400756 -
Food Science & Nutrition Jun 2024Meat intake, particularly from oily fish, has been associated with various chronic diseases. However, its relationship with acne has always been controversial....
Meat intake, particularly from oily fish, has been associated with various chronic diseases. However, its relationship with acne has always been controversial. Therefore, we have adopted Mendelian randomization (MR) analysis to investigate the causal relationship between different types of meat intake and acne. The exposure and outcome datasets for this study were obtained from the Integrative Epidemiology Unit (IEU) Open GWAS project. Seven datasets on meat intake were included, which consisted of non-oily fish, oily fish, lamb/mutton, poultry, pork, beef, and processed meat. The main methods used for MR analysis were inverse variance weighted, weighted median, and MR-egger. To ensure the accuracy of the results, heterogeneity, pleiotropy, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) analyses were conducted. Additionally, an analysis of four risk factors (fasting insulin, insulin resistance, total testosterone level, and estradiol level) was performed to investigate the underlying mechanisms linking statistically significant meat intake to acne. Oily fish intake was found to be a protective factor for acne (OR: 0.22, 95% CI: 0.10-0.49, < .001), and it was also observed that oily fish intake can reduce the level of fasting insulin by the IVW method (OR: 0.89, 95% CI: 0.81-0.98, = .02). No causal relationship was identified between other types of meat intake and acne. The intake of oily fish reduces the risk of acne by lowering fasting insulin levels.
PubMed: 38873457
DOI: 10.1002/fsn3.4054 -
Frontiers in Aging Neuroscience 2024Observational studies have reported inconsistent results on the relationship between chronic kidney disease (CKD) and age-related macular degeneration (AMD). The primary...
PURPOSE
Observational studies have reported inconsistent results on the relationship between chronic kidney disease (CKD) and age-related macular degeneration (AMD). The primary objective of this study was to investigate the causal relationships between estimated glomerular filtration rate (eGFR), CKD, its common causes, and AMD among participants of European descent.
METHODS
Genetic variants associated with eGFR, CKD and its common causes, encompassing diabetic nephropathy (DN), immunoglobulin A nephropathy (IgAN), and membranous nephropathy (MN) were obtained from previously published genome-wide association studies (GWAS) and FinnGen database. Summary statistics for early AMD, AMD, dry AMD, and wet AMD were acquired from the GWAS and FinnGen database. Inverse-variance-weighted (IVW) method was the main MR analysis. Sensitivity analyses were performed with Cochran's Q, MR-Egger intercept, and leave-one-out analysis. In addition, RadialMR was utilized to identify and remove outliers.
RESULTS
IVW results showed that CKD, eGFR were not associated with any type of AMD ( > 0.05). DN (OR: 1.042, 95% CI: 1.002-1.083, = 0.037) and MN (OR: 1.023, 95% CI: 1.007-1.040, = 0.005) were associated with an increased risk of earl AMD. DN (OR: 1.111, 95% CI: 1.07-1.154, = 4.87 × 10), IgAN (OR: 1.373, 95% CI: 1.097-1.719, = 0.006), and MN (OR: 1.036, 95% CI: 1.008-1.064, = 0.012) were associated with an increased risk of AMD. DN (OR: 1.090, 95% CI: 1.042-1.140, = 1.57 × 10) and IgAN (OR: 1.480, 95% CI: 1.178-1.858, = 7.55 × 10) were associated with an increased risk of dry AMD. The risk of wet AMD was associated with DN (OR: 1.107, 95% CI: 1.043-1.174, = 7.56 × 10) and MN (OR: 1.071, 95% CI: 1.040-1.103, = 5.48 × 10).
CONCLUSION
This MR study found no evidence of causal relationship between CKD and AMD. DN, IgAN, and MN may increase risk of AMD. This findings underscore the importance of ocular examinations in patients with DN, MN, and IgAN. More studies are needed to support the findings of our current study.
PubMed: 38872627
DOI: 10.3389/fnagi.2024.1399666