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Frontiers in Nutrition 2023Observational studies suggest that vitamin D supplementation may be effective in preventing myasthenia gravis (MG). However, the causal relationship between circulating...
INTRODUCTION
Observational studies suggest that vitamin D supplementation may be effective in preventing myasthenia gravis (MG). However, the causal relationship between circulating vitamin D levels and MG remains unclear. This study aimed to examine the genetic causality of circulating vitamin D and MG using data from large population-based genome-wide association studies (GWAS).
METHODS
SNPs (single nucleotide polymorphisms) strongly associated with exposure were selected. Two-sample Mendelian Randomization (MR) was performed with inverse variance weighting (IVW), MR-Egger (Mendelian randomization-Egger), weight median and MR-PRESSO (Mendelian randomization pleiotropy residual sum and outlier) methods. Heterogeneity was tested via IVW and MR-Egger. Pleiotropy was tested using MR-Egger intercept test and MR-PRESSO method. MR-PRESSO was also used to detect outliers. Leave-one-out analysis was used to identify SNPs with potential effect. Reverse MR analysis was also performed.
RESULT
In IVW, circulating vitamin D levels had no causal effect on MG [OR = 0.91 (0.67-1.22), = 0.532] and MG had no causal effect on circulating vitamin D [OR = 1.01 (099-1.02), = 0.663]. No heterogeneity or pleiotropy was observed ( > 0.05). Other MR methods also agreed with IVW results.
CONCLUSION
This study provides the causal relationship between genetically predicted circulating vitamin D levels and MG and provides new insights into the genetics of MG.
PubMed: 37538922
DOI: 10.3389/fnut.2023.1171830 -
Aging Dec 2023While observational studies have suggested a link between cognitive performance and fracture risk, the causality and site-specific nature are unclear. We applied...
OBJECTIVE
While observational studies have suggested a link between cognitive performance and fracture risk, the causality and site-specific nature are unclear. We applied Mendelian randomization (MR) to elucidate these associations.
METHODS
147 single-nucleotide polymorphisms (SNPs) tied strongly to cognitive performance (< 5e-8) were selected. We performed MR analysis to investigate the causal relationship between cognitive performance and fractures at specific sites, including the wrist, upper arm, shoulder, ribs, sternum, thoracic spine, lumbar spine, pelvis, femur, leg, and ankle. The primary estimate was determined using the inverse variance-weighted method. Additionally, we examined heterogeneity using the MR Pleiotropy RESidual Sum Outlier test and Cochran Q, and employed MR-Egger regression to identify horizontal pleiotropy.
RESULTS
MR analysis identified a causal association between cognitive performance and fractures at the lumbar-spine-pelvis (odds ratio [OR] = 0.727, 95% CI = 0.552-0.956, = 0.023), and ribs-sternum-thoracic spine sites (OR = 0.774, 95% CI = 0.615-0.974, = 0.029). However, no causal association was found for fractures at other sites.
CONCLUSIONS
This study provided evidence of a causal connection between cognitive performance and fracture risk at certain locations. These findings underline the potential of cognitive enhancement strategies as innovative and effective methods for fracture prevention.
Topics: Humans; Mendelian Randomization Analysis; Lumbar Vertebrae; Femur; Fractures, Bone; Cognition; Genome-Wide Association Study
PubMed: 38112588
DOI: 10.18632/aging.205325 -
Frontiers in Digital Health 2023This paper compares three finite element-based methods used in a physics-based non-rigid registration approach and reports on the progress made over the last 15 years.... (Review)
Review
This paper compares three finite element-based methods used in a physics-based non-rigid registration approach and reports on the progress made over the last 15 years. Large brain shifts caused by brain tumor removal affect registration accuracy by creating point and element outliers. A combination of approximation- and geometry-based point and element outlier rejection improves the rigid registration error by 2.5 mm and meets the real-time constraints (4 min). In addition, the paper raises several questions and presents two open problems for the robust estimation and improvement of registration error in the presence of outliers due to sparse, noisy, and incomplete data. It concludes with preliminary results on leveraging Quantum Computing, a promising new technology for computationally intensive problems like Feature Detection and Block Matching in addition to finite element solver; all three account for 75% of computing time in deformable registration.
PubMed: 38144260
DOI: 10.3389/fdgth.2023.1283726 -
Frontiers in Nutrition 2023Current studies have reported conflicting associations between circulating micronutrient levels and kidney stone disease (KSD). We aimed to elucidate the causal...
BACKGROUND
Current studies have reported conflicting associations between circulating micronutrient levels and kidney stone disease (KSD). We aimed to elucidate the causal relationship between circulating micronutrient levels and KSD by a two-sample Mendelian randomization (MR) analysis.
METHODS
Total of 36 single nucleotide polymorphisms (SNPs) from published genome-wide association studies (GWAS) significantly associated with eight micronutrients (vitamin B12, folic acid, magnesium, iron, phosphorus, copper, zinc, and selenium) were used as instrumental variables. The GWAS summary data associated with KSD (8,060 cases and 301,094 controls) were obtained from the FinnGen consortium. Inverse variance weighted was the main MR analysis method. MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), weighted median and MR-Egger were used to assess pleiotropy and heterogeneity.
RESULTS
Genetically predicted circulating vitamin B12 and zinc levels were causally associated with the risk of KSD (vitamin B12: OR: 1.17, 95% CI: 1.04-1.32, = 0.008; zinc: OR: 1.15, 95% CI: 1.03-1.28, = 0.015). We found no evidence that other circulating micronutrients were associated with risk of KSD. -value for Cochrane test, MR Egger intercept test, and MR-PRESSO were >0.05, indicating no significant heterogeneity or horizontal pleiotropy in this MR analysis.
CONCLUSION
Increasing circulating zinc levels may increase the risk of KSD. More studies are needed to provide evidence on whether genetically predicted circulating vitamin B12 and zinc levels are a risk factor for KSD.
PubMed: 37671199
DOI: 10.3389/fnut.2023.1132597 -
BMC Medical Research Methodology Oct 2023Growth studies rely on longitudinal measurements, typically represented as trajectories. However, anthropometry is prone to errors that can generate outliers. While...
BACKGROUND
Growth studies rely on longitudinal measurements, typically represented as trajectories. However, anthropometry is prone to errors that can generate outliers. While various methods are available for detecting outlier measurements, a gold standard has yet to be identified, and there is no established method for outlying trajectories. Thus, outlier types and their effects on growth pattern detection still need to be investigated. This work aimed to assess the performance of six methods at detecting different types of outliers, propose two novel methods for outlier trajectory detection and evaluate how outliers affect growth pattern detection.
METHODS
We included 393 healthy infants from The Applied Research Group for Kids (TARGet Kids!) cohort and 1651 children with severe malnutrition from the co-trimoxazole prophylaxis clinical trial. We injected outliers of three types and six intensities and applied four outlier detection methods for measurements (model-based and World Health Organization cut-offs-based) and two for trajectories. We also assessed growth pattern detection before and after outlier injection using time series clustering and latent class mixed models. Error type, intensity, and population affected method performance.
RESULTS
Model-based outlier detection methods performed best for measurements with precision between 5.72-99.89%, especially for low and moderate error intensities. The clustering-based outlier trajectory method had high precision of 14.93-99.12%. Combining methods improved the detection rate to 21.82% in outlier measurements. Finally, when comparing growth groups with and without outliers, the outliers were shown to alter group membership by 57.9 -79.04%.
CONCLUSIONS
World Health Organization cut-off-based techniques were shown to perform well in few very particular cases (extreme errors of high intensity), while model-based techniques performed well, especially for moderate errors of low intensity. Clustering-based outlier trajectory detection performed exceptionally well across all types and intensities of errors, indicating a potential strategic change in how outliers in growth data are viewed. Finally, the importance of detecting outliers was shown, given its impact on children growth studies, as demonstrated by comparing results of growth group detection.
Topics: Child; Humans; Cluster Analysis; Research Design; Infant; Child Development
PubMed: 37833647
DOI: 10.1186/s12874-023-02045-w -
Frontiers in Immunology 2023The immune response assumes a pivotal role in the underlying mechanisms of urticaria pathogenesis. The present study delves into an investigation of the genetic causal...
OBJECTIVE
The immune response assumes a pivotal role in the underlying mechanisms of urticaria pathogenesis. The present study delves into an investigation of the genetic causal connections between urticaria and prevalent autoimmune afflictions, notably rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ulcerative colitis (UC), and Crohn's disease (CD).
METHODS
A bidirectional two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationships involving four autoimmune diseases and urticaria. The genome-wide association study (GWAS) summary data of four autoimmune disease were sourced from the IEU OpenGWAS database. The GWAS summary data for urticaria were derived from the Finnish consortium dataset. The principal analytical approach employed in this study was the random-effects inverse variance weighted (IVW) method. Subsequently, a series of sensitivity analyses were performed, encompassing assessments of heterogeneity, horizontal pleiotropy, outliers, "Leave-one-out" analyses, and tests for adherence to the assumption of normal distribution.
RESULTS
The random-effects IVW analysis indicate a positive genetic causal association between RA and urticaria (P < 0.001, OR 95% CI = 1.091 [1.051-1.133]). Conversely, SLE, UC, and CD do not exhibit a significant genetic causal relationship with urticaria. The reverse MR analysis reveals a positive genetic causal linkage between urticaria and SLE (P = 0.026, OR 95% CI = 1.289 [1.031-1.612]). However, the analysis demonstrates no substantial genetic causal relationship between urticaria and RA, UC, or CD. Importantly, the genetic causal assessment absence of heterogeneity, horizontal pleiotropy, and outliers. Furthermore, it remains unaffected by any individual single nucleotide polymorphism (SNP), demonstrating adherence to a normal distribution.
CONCLUSION
This investigation establishing RA as a predisposing factor for urticaria. Moreover, urticaria as a plausible risk determinant for SLE. Heightened vigilance is recommended among RA patients to monitor the manifestation of urticaria within clinical settings. Similarly, individuals afflicted by urticaria should duly acknowledge the prospective susceptibility to SLE.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Prospective Studies; Autoimmune Diseases; Arthritis, Rheumatoid; Lupus Erythematosus, Systemic; Causality; Colitis, Ulcerative; Crohn Disease
PubMed: 38022623
DOI: 10.3389/fimmu.2023.1280135 -
Brain and Behavior Nov 2023Patients with autism spectrum disorder (ASD) commonly experience aberrant skin sensation sensitivity; however, the causal relationship is not yet clear. This study uses...
BACKGROUND AND AIM
Patients with autism spectrum disorder (ASD) commonly experience aberrant skin sensation sensitivity; however, the causal relationship is not yet clear. This study uses a bidirectional Mendelian randomization (MR) method to explore the relationship between disturbance of skin sensation (DSS) and ASD.
METHODS
Single-nucleotide polymorphisms (SNPs) extracted from the summary data of genome-wide association studies were used as genetic instruments. MR was performed using the inverse-variance-weighted method, with alternate methods (e.g., weighted median, MR-Egger, simple mode, weighted mode, and MR-pleiotropy residual sum and outlier) and multiple sensitivity analyses to assess horizontal pleiotropy and remove outliers.
RESULTS
The results of the analysis using six SNPs as genetic instruments showed that the DSS is associated with an increased risk of ASD (odds ratio = 1.126, 95% confidence interval = 1.029-1.132; p = .010). The results of the sensitivity analyses were robust with no evidence of pleiotropy. The reverse MR analyses showed no causal effects of ASD on DSS.
CONCLUSION
This study's findings suggest that DSS has potential causal effects on ASD, whereas ASD has no effect on DSS. Thus, skin sensitivity may represent a behavioral marker of ASD, by which some populations could be subtyped in the future.
Topics: Humans; Autism Spectrum Disorder; Genome-Wide Association Study; Mendelian Randomization Analysis; Skin; Sensation
PubMed: 37670485
DOI: 10.1002/brb3.3238 -
Causal relationship between dietary factors and breast cancer risk: A Mendelian randomization study.Heliyon Oct 2023Previous studies have discovered an association between dietary factors and breast cancer. However, few studies have used Mendelian randomization (MR) to assess the...
BACKGROUND
Previous studies have discovered an association between dietary factors and breast cancer. However, few studies have used Mendelian randomization (MR) to assess the potential causal relationship between dietary factors and breast cancer.
METHODS
The exposure datasets for fresh fruit intake, dried fruit intake, salad/raw vegetable intake, cooked vegetable intake, oily fish intake, non-oily fish intake, cheese intake, and bread intake were obtained from the UK Biobank. The outcome dataset was extracted from the Breast Cancer Association Consortium (BCAC). We used the inverse variance weighted (IVW) method as the primary approach for the two-sample MR analysis. To ensure the accuracy of the results, we conducted heterogeneity and horizontal pleiotropy analyses. Additionally, multivariable MR analysis was conducted to ensure the stability of the results.
RESULTS
Dried fruit intake was found to be a protective factor for overall breast cancer (outliers excluded: OR: 0.549; 95 % CI: 0.429-0.702; p = 1.75 × 10). Subtype analyses showed that dried fruit intake was inversely associated with both estrogen receptor-positive (ER+) breast cancer (outliers excluded: OR: 0.669; 95 % CI: 0.512-0.875; p = 0.003) and ER-negative (ER-) breast cancer (OR: 0.559; 95 % CI: 0.379-0.827; p = 0.004), while fresh fruit intake was inversely associated with ER- breast cancer (excluded outliers: OR: 0.510; 95 % CI: 0.308-0.846; p = 0.009). No significant causal relationship was found between other dietary intakes and breast cancer. After adjusting for the effects of possible confounders, the causal relationships found by the two-sample MR analysis remained.
CONCLUSION
Our study provides evidence that dried fruit intake may reduce the risk of both ER+ and ER- breast cancer, and fresh fruit intake may reduce the risk of ER- breast cancer. Other factors included in this study were not linked to breast cancer.
PubMed: 37867896
DOI: 10.1016/j.heliyon.2023.e20980 -
Frontiers in Nutrition 2023Previous studies have not established potential causal associations between coffee and caffeine consumption in endometrial cancer (EC) and its subgroups. Therefore, we...
BACKGROUND
Previous studies have not established potential causal associations between coffee and caffeine consumption in endometrial cancer (EC) and its subgroups. Therefore, we used a two-sample MR method to assess the causal association between coffee and caffeine consumption and EC risk. We also evaluated the association between these genetically predicted exposures and EC prognosis.
MATERIALS AND METHODS
This study used 12 and two independent single-nucleotide polymorphisms (SNPs) associated with coffee and caffeine consumption as instrumental variables at a genome-wide significance level of < 5 × 10. The EC Association Consortium (ECAC) performed a genome-wide association study (GWAS) analysis of 12,906 cases and 108,979 controls. FinnGen Consortium performed a GWAS analysis of 1,967 EC cases and 167,189 controls. The primary technique we employed was inverse-variance weighted, followed by the weighted median, MR-Egger regression, and MR robust adjusted profile score methods. We used the MR pleiotropy residual sum, Outlier test, and MR-Egger regression to assess Outlier and pleiotropic variants. We also conducted a sensitivity analysis through the leave-one-out method.
RESULTS
Genetically predicted coffee consumption was not associated with EC and its subgroups in the ECAC, and the association was consistent in the FinnGen consortium. After excluding eight SNPs with confounding factors, the study performed sensitivity analyses, delivering consistent results. We also observed that caffeine consumption was not correlated with EC risk. As confirmed by MR analysis, selected SNPs determined that most do not significantly impact the likelihood of developing EC.
CONCLUSION
Our study indicated no convincing evidence supports coffee and caffeine consumption causing EC or impacting its prognosis. More studies are needed to validate the results.
PubMed: 38035346
DOI: 10.3389/fnut.2023.1291355 -
BioRxiv : the Preprint Server For... Apr 2024Cancer is pervasive across multicellular species, but what explains differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species...
Cancer is pervasive across multicellular species, but what explains differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades (amphibians, sauropsids and mammals) we found that neoplasia and malignancy prevalence increases with adult weight (contrary to Petos Paradox) and somatic mutation rate, but decreases with gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%) the black-footed penguin (<0.4%), ferrets (63%) and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer.
PubMed: 36824942
DOI: 10.1101/2023.02.15.527881