Causal links between immune cells and asthma: Insights from a Mendelian Randomization analysis.

OBJECTIVES: Recent studies suggest immunophenotypes may play a role in asthma, but their causal relationship has not been thoroughly examined. METHODS: We used single nucleotide polymorphism (SNP)-derived instrumental variables. Summary data from 731 immune cell profiles and asthma cases were analyzed from genome-wide association studies (GWAS) of European populations. Mendelian Randomization (MR) analyses included inverse variance weighted (IVW), weighted median, and MR-Egger methods. Pleiotropy was assessed using the MR-Egger intercept and MR pleiotropy residual sum and outlier (MR-PRESSO) tests. Reverse MR analysis explored bidirectional causation between asthma and immunophenotypes. All statistical analyses were conducted using R software. RESULTS: MR analysis identified 108 immune signatures potentially contributing to asthma. Two immunophenotypes were significantly associated with asthma risk: CD4+ secreting Treg cells in allergic asthma (ORIVW = 1.078; 95% CI: 1.036-1.122; PIVW = 0.0002) and IgD + CD38- %lymphocyte cells in non-allergic asthma (ORIVW = 1.123; 95% CI: 1.057-1.194; PIVW = 0.0002). CONCLUSIONS: This study highlights the causal associations between specific immunophenotypes and asthma risk, providing new insights into asthma pathogenesis.

Causal Relationships Between Retinal Diseases and Psychiatric Disorders Have Implications for Precision Psychiatry.

Observational studies and clinical trials have reported potential associations between retinal diseases and psychiatric disorders. However, the causal associations between them have remained elusive. In this study, we used bi-directional two-sample Mendelian randomization (MR) analysis to explore unconfounded causal relationships between retinal diseases and psychiatric disorders using large-scale genome-wide association study (GWAS) summary statistics of over 500,000 participants of European ancestry from the FinnGen project, the Psychiatric Genomics Consortium, the European Bioinformatics Institute, and the UK Biobank. Our MR analysis revealed significant causal relationships between major retinal diseases and specific psychiatric disorders. Specifically, susceptibility to dry age-related macular degeneration was associated with a reduced risk of anorexia nervosa (OR = 0.970; 95% CI = 0.930 ~ 0.994; P = 0.025). Furthermore, we found some evidence that exposure to diabetic retinopathy was associated with an increased risk of schizophrenia (OR = 1.021; 95% CI 1.012 ~ 1.049; P = 0.001), and exposure to retinal detachments and breaks was associated with an increased risk of attention deficit hyperactivity disorder (OR = 1.190; 95% CI 1.063 ~ 1.333; P = 0.003). These causal relationships were not confounded by biases of pleiotropy and reverse causation. Our study highlights the importance of preventing and managing retinal disease as a potential avenue for improving the prevention, management and treatment of major psychiatric disorders.

Interplay between immune cells and metabolites in epilepsy: insights from a Mendelian randomization analysis.

Background: Epilepsy is associated with the immune system and metabolism; however, its etiology remains insufficiently understood. Here, we aim to elucidate whether circulating immune cell profiles and metabolites impact the susceptibility to epilepsy. Methods: We used publicly available genetic data and two-sample Mendelian randomization (MR) analyses to establish causal relationships and mediating effects between 731 immune cells and 1,400 metabolites associated with epilepsy. Sensitivity analyses were conducted to detect heterogeneity and horizontal pleiotropy in the study results. Results: MR analysis examining the relationship between immune cells, metabolites, and epilepsy revealed significant causal associations with 28 different subtypes of immune cells and 14 metabolites. Besides, the mediation effects analysis revealed that eight metabolites mediated the effects of six types of immune cells on epilepsy and that 3-hydroxyoctanoylcarnitine (2) levels exhibited the highest mediating effect, mediating 15.3% (95%CI, -0.008, -30.6%, p = 0.049) of the effect of DN (CD4-CD8-) AC on epilepsy. 1-(1-enyl-stearoyl)-2-linoleoyl-GPE (p-18:0/18:2) levels (95%CI, 0.668, 10.6%, p = 0.026) and X-12544 levels (95%CI, -15.1, -0.856%, p = 0.028) contributed 5.63 and 8%, respectively, to the causal effect of FSC-A on myeloid DC on epilepsy. Conclusion: This study revealed a significant causal link between immune cells, metabolites, and epilepsy. It remarkably enhances our understanding of the interplay between immune responses, metabolites, and epilepsy risk, providing insights into the development of therapeutic strategies from both immune and metabolic perspectives.

The relationship between metabolite mediated immune regulatory imbalance and the occurrence of malignant tumors of bone and articular cartilage: a Mendelian randomization study.

Background: This study aims to assess the causal relationship between immune cell characteristics and malignant tumors of bone and articular cartilage, focusing on the mediating role of metabolites. Using Mendelian randomization, we evaluated these relationships based on genetic variations to identify potential biomarkers and therapeutic targets. Methods: A two-sample Mendelian randomization analysis was conducted using GWAS data for immune cell features and 1,400 metabolites to investigate direct and mediating effects. Effective instrumental variables (IVs) were selected, and statistical analyses-including inverse variance weighting (IVW), weighted median, and mode-based methods-were performed using R software. This approach enabled the assessment of direct causal relationships as well as the potential mediating role of metabolites in the association between immune cell features and malignancies. Results: Significant causal relationships were identified between 26 immune phenotypes and the risk of malignant tumors of bone and articular cartilage. Notably, the HLA DR+ NK cell phenotype SSC-A showed a positive correlation with the risk of these malignancies. Further analysis revealed causal relationships with 67 metabolites, 38 of which were positively correlated and 29 negatively correlated. Mediation analysis highlighted the role of immune surveillance and metabolic dysregulation in tumor development, as evidenced by the association between the immune phenotype SSC-A on HLA DR+ NK cells and the metabolite 5-hydroxyhexanoate. Conclusion: The findings suggest significant causal relationships between immune phenotypes and malignant tumors of bone and articular cartilage, with metabolites potentially mediating these relationships. These insights lay the groundwork for further research and could contribute to the development of new biomarkers and treatment strategies.

Appraising the effectiveness of immune cells on thyroid cancer: a Mendelian randomization study.

BACKGROUND: The intricate interplay between the immune system and tumor plays a pivotal role in thyroid cancer (TC) pathogenesis, potentially influencing both the causation and therapeutic outcomes. Despite extensive research, existing literature offers ambiguous insights regarding the association between immune cell traits and thyroid cancer progression. METHODS: To elucidate the potential causal relationships, we conducted an integrated two-sample Mendelian randomization (MR) analysis. This study utilized publicly genetic datasets to explore the causalities between 731 immune cell traits (categorized into four trait types across seven panels) and thyroid cancer. We ensured the robustness of our findings through comprehensive sensitivity analyses, meticulously assessing potential sources of bias such as pleiotropy. RESULTS: After False Discovery Rate (FDR) correction, six immune cell traits were identified to be significantly associated with thyroid cancer risk (Inverse Variance Weighted, IVW): Absolute count of gamma delta T cells/ T-cell receptor gamma delta absolute count (TCRgd AC) 0.8464 (OR95% CI = 0.7477-0.9580, P = 0.0083, PFDR = 0.0103); CD8 on bright CD8 cells (CD8 on CD8br) 0.8867 (OR95% CI = 0.8159-0.9637, P = 0.0047, PFDR = 0.0093); CD127 on CD45RA negative CD4 T cells not regulatory T cells (CD127 on CD45RA- CD4 not Treg) 0.8969 (OR95% CI = 0.8192-0.9820, P = 0.0186, PFDR = 0.0186); CD80 on CD62L positive plasmacytoid dendritic cells (CD80 on CD62L+ plasmacytoid DC) 1.1091 (OR95% CI = 1.0267-1.1982, P = 0.0086, PFDR = 0.0103); CD80 on plasmacytoid DC 1.1283 (OR95% CI = 1.0462-1.2168, P = 0.0017, PFDR = 0.0093); Side scatter-area on bright CD8 cells (SSC - A on CD8br) 1.1622 (OR95% CI = 1.0507-1.2854, P = 0.0035, PFDR = 0.0093). CONCLUSIONS: Our study demonstrated the causalities between immune cell traits and thyroid cancers by Mendelian randomization study, thus guiding future mechanism studies.

Estimating the prevalence and clinical causality of obstructive sleep apnea in paediatric narcolepsy patients.

BACKGROUND: Numerous risk factors in paediatric narcolepsy may predispose them to obstructive sleep apnea (OSA). The concurrent presence of OSA in these patients might lead to underdiagnosing narcolepsy. This research investigates the prevalence and potential causality between OSA and paediatric narcolepsy. METHODS: A case-control study coupled with a two-sample Mendelian randomization (MR) analysis was employed to explore the prevalence and causal link between paediatric narcolepsy and OSA risk. RESULTS: The case-control study revealed that paediatric narcolepsy patients are at an increased risk of OSA, with an Odds ratio (OR) of 4.87 (95% CI: 2.20-10.71; P < 0.001). The inverse-variance weighted (IVW) model further suggests a potential causal link between narcolepsy and OSA (IVW OR: 4.671, 95% CI: 1.925-11.290; P < 0.001). Additionally, sensitivity analysis confirmed these findings' reliability. CONCLUSION: The findings highlight an elevated prevalence and genetic susceptibility to OSA among paediatric narcolepsy patients, underscoring the necessity for clinical screening of OSA. Continued research is essential to clarify the pathogenic mechanisms and develop potential treatments.

Association between levels of sex hormones and risk of multiple sclerosis: a mendelian randomization study.

BACKGROUND: This research aimed to examine the causal connections between multiple sclerosis (MS) and a range of sex hormone-related traits, such as bioavailable testosterone (BT), sex hormone-binding globulin (SHBG), testosterone, and estradiol (E2). METHODS: A bidirectional two-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies (GWAS) was conducted to investigate the relationship between sex hormone-related traits and MS. Moreover, the Inverse-variance weighted (IVW) method was employed as the primary analysis approach. RESULTS: The MR analysis, using the IVW method, found a significant correlation between genetically determined SHBG levels and MS (OR = 1.634, 95% CI: 1.029-2.599, p = 0.038). Similarly, the reverse MR analysis suggested a causal link between MS and SHBG (OR = 1.005, 95% CI: 1.001-1.009, P = 0.003). However, no association was observed between MS risk and E2, testosterone, or BT levels. CONCLUSION: Our MR analysis demonstrated that genetically predicted higher SHBG may be positively correlated with the risk of MS. Moreover, the role of SHBG in MS could be further investigated.

Unraveling the causal relationships between depression and brain structural imaging phenotypes: A bidirectional Mendelian Randomization study.

BACKGROUND: Previous studies have revealed structural brain abnormalities in individuals with depression, but the causal relationship between depression and brain structure remains unclear. METHODS: A genetic correlation analysis was conducted using summary statistics from the largest genome-wide association studies for depression (N = 674,452) and 1,265 brain structural imaging-derived phenotypes (IDPs, N = 33,224). Subsequently, a bidirectional two-sample Mendelian Randomization (MR) approach was employed to explore the causal relationships between depression and the IDPs that showed genetic correlations with depression. The main MR results were obtained using the inverse variance weighted (IVW) method, and other MR methods were further employed to ensure the reliability of the findings. RESULTS: Ninety structural IDPs were identified as being genetically correlated with depression and were included in the MR analyses. The IVW MR results indicated that reductions in the volume of several brain regions, including the bilateral subcallosal cortex, right medial orbitofrontal cortex, and right middle-posterior part of the cingulate cortex, were causally linked to an increased risk of depression. Additionally, decreases in surface area of the right middle temporal visual area, right middle temporal cortex, right inferior temporal cortex, and right middle-posterior part of the cingulate cortex were causally associated with a heightened risk of depression. Validation and sensitivity analyses supported the robustness of these findings. However, no evidence was found for a causal effect of depression on structural IDPs. CONCLUSIONS: Our findings reveal the causal influence of specific brain structures on depression, providing evidence to consider brain structural changes in the etiology and treatment of depression.

Dissecting the genetic and causal relationship between sleep-related traits and common brain disorders.

BACKGROUND: There is a profound connection between abnormal sleep patterns and brain disorders, suggesting a shared influential association. However, the shared genetic basis and potential causal relationships between sleep-related traits and brain disorders are yet to be fully elucidated. METHODS: Utilizing linkage disequilibrium score regression (LDSC) and bidirectional two-sample univariable Mendelian Randomization (UVMR) analyses with large-scale GWAS datasets, we investigated the genetic correlations and causal associations across six sleep traits and 24 prevalent brain disorders. Additionally, a multivariable Mendelian Randomization (MVMR) analysis evaluated the cumulative effects of various sleep traits on each brain disorder, complemented by genetic loci characterization to pinpoint pertinent genes and pathways. RESULTS: LDSC analysis identified significant genetic correlations in 66 out of 144 (45.8 %) pairs between sleep-related traits and brain disorders, with the most pronounced correlations observed in psychiatric disorders (66 %, 48/72). UVMR analysis identified 29 causal relationships (FDR<0.05) between sleep traits and brain disorders, with 19 associations newly discovered according to our knowledge. Notably, major depression, attention-deficit/hyperactivity disorder, bipolar disorder, cannabis use disorder, and anorexia nervosa showed bidirectional causal relations with sleep traits, especially insomnia's marked influence on major depression (IVW beta 0.468, FDR = 5.24E-09). MVMR analysis revealed a nuanced interplay among various sleep traits and their impact on brain disorders. Genetic loci characterization underscored potential genes, such as HOXB2, while further enrichment analyses illuminated the importance of synaptic processes in these relationships. CONCLUSIONS: This study provides compelling evidence for the causal relationships and shared genetic backgrounds between common sleep-related traits and brain disorders.

Causal relationship between narcolepsy and anxiety: A two-sample Mendelian randomization study.

BACKGROUND: The aim of this study was to assess the causal relationship between narcolepsy and anxiety using Mendelian randomization (MR) methodology. METHODS: Our research applied a bidirectional two-sample Mendelian Randomization strategy to explore the linkage between narcolepsy and anxiety. Utilizing summary data from GWAS on both conditions, we primarily employed the inverse-variance weighted technique for our analysis. To evaluate heterogeneity and horizontal pleiotropy, we utilized tools such as the MR Egger method, the weighted median method, Cochran's Q statistic, and the MR Egger intercept. RESULTS: The analysis using the inverse variance-weighted method showed a clear positive link between narcolepsy and anxiety, with an odds ratio of 1.381 (95% CI: 1.161-1.642, p < 0.001). Tests for heterogeneity and horizontal pleiotropy, including MR Egger and IVW methods, indicated no significant findings (p-values 0.616 and 0.637, respectively, for heterogeneity; p = 0.463 for pleiotropy). Furthermore, no reverse causation was observed between anxiety and narcolepsy (odds ratio 1.034, 95% CI: 0.992-1.078, p = 0.111), with consistent findings across various analytical approaches. CONCLUSION: This research suggests a possible causal link between narcolepsy and anxiety disorders. The results illuminate this connection and advocate additional studies to elucidate the mechanisms involved and to identify effective interventions.

Multiple coronary heart diseases are risk factors for mental health disorders: A mendelian randomization study.

BACKGROUND: Previous observational studies have suggested associations between Coronary Heart Disease (CHD) and Mental Health Disorders (MHD). However, the causal nature of these relationships has remained elusive. OBJECTIVE: The purpose of this study is to elucidate the causal relationships between eight distinct types of CHD and six types of MHD using Mendelian randomization (MR) analysis. METHODS: The MR analysis employed a suite of methods including inverse variance-weighted (IVW), MR-Egger, weighted mode, weighted median, and simple mode techniques. To assess heterogeneity, IVW and MR-Egger tests were utilized. MR-Egger regression also served to investigate potential pleiotropy. The stability of IVW results was verified by leave-one-out sensitivity analysis. RESULTS: We analyzed data from over 2,473,005 CHD and 803,801 MHD patients, informed by instrumental variables from large-scale genomic studies on European populations. The analysis revealed a causal increase in the risk of Major Depressive Disorder and Mania associated with Coronary Artery Disease and Myocardial Infarction. Heart Failure was found to causally increase the risk for Bipolar Disorder and Schizophrenia. Atrial Fibrillation and Ischemic Heart Diseases were positively linked to Generalized Anxiety Disorder and Mania, respectively. There was no significant evidence of an association between Hypertensive Heart Disease, Hypertrophic Cardiomyopathy, Pulmonary Heart Disease, and MHD. Reverse MR analysis indicated that MHD do not serve as risk factors for CHD. CONCLUSIONS: The findings suggest that specific types of CHD may act as risk factors for certain MHDs. Consequently, incorporating psychological assessments into the management of patients with CHD could be advantageous.

Investigating causal relationships between extensive peripheral immune cell phenotypes and preeclampsia: A bi-directional Mendelian randomization analysis.

PROBLEM: Preeclampsia, a multifaceted condition during pregnancy characterized by hypertension and organ dysfunction, poses significant risks to both maternal and fetal health. This study aims to investigate the bidirectional causal relationship between peripheral immune cell phenotypes and preeclampsia using a two-sample Mendelian randomization (MR) approach. METHOD OF STUDY: Genetic data from two sizable cohorts were utilized: 3757 individuals from Sardinia, providing information on 731 immune traits, and 200 929 Finnish adult females, encompassing 6663 preeclampsia cases. Single-nucleotide polymorphisms served as instrumental variables. The MR analyses employed the inverse variance-weighted (IVW) method as the primary tool, supplemented by MR-Egger, weighted median, and weighted mode methods to enhance reliability and address potential heterogeneity and horizontal pleiotropy. RESULTS: Among the 731 immune cell phenotypes studied, 18 displayed a suggestive positive association (IVW p < .05) with heightened preeclampsia risk, while 20 exhibited a suggestive negative association linked to reduced risk. Following false discovery rate (FDR) adjustment, four immune phenotypes showed significant associations with decreased preeclampsia risk: CD27 on CD24+ CD27+ B cells (B-cell panel) (odds ratio [OR] = 0.927, PFDR = 0.061), CD33+ HLA DR+ CD14- absolute count (OR = 0.963, PFDR = 0.061), CD80 on plasmacytoid dendritic cells (OR = 0.923, PFDR = 0.061); and CD80 on CD62L+ plasmacytoid dendritic cells (OR = 0.923, PFDR = 0.061). In the reverse-direction MR analysis, no significant causal effects of preeclampsia on immune cell phenotypes were observed. CONCLUSIONS: This study provides quantifiable evidence linking specific immune cell phenotypes to the risk of developing preeclampsia. This novel understanding of the immunological aspects underlying preeclampsia's pathogenesis could lead to innovative therapeutic strategies centered on immune modulation.

Association between vitamin B12 deficiency and risk of Paediatric narcolepsy: Evidence from cross-sectional study and Mendelian randomization analysis.

BACKGROUND: Narcolepsy, a chronic neurologic sleep disorder, has sparked growing interest in the potential role of vitamin B12 in its pathogenic mechanism. However, research on this association has predominantly focused on adults. Our objective was to delineate the phenotypic and genetic connections between serum vitamin B12 levels and paediatric narcolepsy. METHODS: To investigate the causal relationship between vitamin B12 and paediatric narcolepsy, we conducted a retrospective analysis involving 60 narcolepsy patients and a matched control group. Univariate and multivariate logistic regression models were employed to identify independent factors influencing paediatric narcolepsy. Furthermore, a bidirectional two-sample Mendelian randomization (MR) analysis was performed to assess the causal connection between serum vitamin B12 levels and narcolepsy. RESULTS: Paediatric narcolepsy patients showed significantly lower serum levels of vitamin B12 and folate compared to the control group (P < 0.05). Multivariate logistic regression analysis identified serum vitamin B12 as the exclusive independent factor influencing paediatric narcolepsy (P < 0.001; OR = 0.96; 95%CI: 0.94-0.98). Additionally, IVW model results provided compelling evidence supporting a potential causal association between serum vitamin B12 levels and paediatric narcolepsy (OR: 0.958, 95% CI = 0.946-0.969, P = 0.001). CONCLUSION: This study establishes connections at both phenotypic and genetic levels, associating vitamin B12 deficiency with an increased risk of paediatric narcolepsy. These findings provide innovative perspectives for clinical strategies in the prevention and treatment of narcolepsy.

Mendelian Randomization Validates the Immune Landscape Mediated by Aggrephagy in Esophageal Squamous Cell Carcinoma Patients from the Perspectives of Multi-omics.

Objective: To delineate the immune landscape of ESCC patients mediated by aggrephagy through bioinformatics and identify prognostic cell cluster genes with causal attributes to esophageal cancer through Mendelian randomization. Methods: Quality control, dimension reduction, and annotation were performed on the ESCC single-cell dataset. NMF clustering of various cell subgroups was carried out based on the expression of AGG-related genes, and AGG-related genes in each cluster were identified. Pseudo-temporal analysis was used to observe changes in the expression of AGG-related genes in each cluster. Cell communication analysis was employed to observe interactions between cell subgroups. Changes in classification, metabolism, or KEGG pathways in related subgroups were observed based on different cell characteristics. The AGG cluster attributes of TCGA and GEO samples were assessed based on GSVA, and the prognosis of each cluster was observed. The immune treatment situation and the relationship between mutation level and prognosis of AGG cluster-related samples were observed through the TIDE database and microsatellite instability. Finally, the eQTL of genes in each prognostic AGG cluster was used as an instrumental variable, with esophageal cancer as the outcome factor. Through Mendelian randomization analysis, AGG cluster-related genes with a causal relationship to esophageal cancer were established. Results: Dimension reduction clustering of single-cell transcriptome data identified 19 different cell subgroups. After re-annotation of the 19 cell subgroups, it was found that the CAF cells, B cells, T cells, NK cells, etc., of ESCA patients were all elevated compared to the control group. CAF cells had a high degree of communication with most cells. There were significant differences in macrophage metabolism and B-cell-mediated signal transduction pathways in different AGG clusters. The TUBA1B+Mac-C0 cluster, along with other clusters, exhibits predictive prognostic and immunotherapeutic potential at the transcriptional level. Mendelian randomization analysis revealed a causal relationship between genes such as CTSZ, CTSC, DAD, COLEC12, ATOX1, within the AGG cluster, and the onset of esophageal cancer. Conclusion: Aggrephagy mediates and influences the alterations and interactions of various immune cells in patients with ESCC. We elucidate the roles of AGG-related clusters, such as TUBA1B+Mac-C0, VIM+CD8+T_cells-C0, UBB+Mac-C2, in mediating prognosis and immune therapy in ESCC patients. Genes causally associated with the occurrence of esophageal cancer are identified within the AGG cluster, including CTSZ, CTSC, DAD, COLEC12, ATOX1, etc., offering new evidence for clinical immune therapy. These findings underscore the significance of these gene clusters in influencing both prognosis and immune responses in the context of esophageal cancer, shedding light on potential therapeutic targets and prognostic markers.

Causal relationships between delirium and Parkinson's disease: a bidirectional two-sample Mendelian randomization study.

BACKGROUND: Previous observational studies have suggested a notably elevated prevalence of delirium in individuals diagnosed with Parkinson's disease (PD), thereby implying a potential increased susceptibility to delirium among PD patients. However, it is imperative to acknowledge that observational studies inherently possess limitations, rendering it arduous to establish a definitive causal or reverse causal association between delirium and PD. METHODS: To explore the relationship between delirium and PD, a bidirectional two-sample Mendelian randomization (MR) was conducted using summary statistics obtained from genome-wide association studies. The main analysis was performed using the inverse-variance weighted (IVW) method, with further analyses conducted using MR Egger, weighted median, and weighted mode to ensure accuracy of findings. Additionally, Cochran's Q statistics and MR Egger intercept were utilized to assess heterogeneity and horizontal pleiotropy, respectively. RESULTS: According to the results obtained from the IVW model, no compelling evidence was found to support a potential causal association between delirium and PD (IVW: odds ratio [OR]: 0.996, 95% confidence interval CI 0.949-1.043, P = 0.845). Additionally, in the reverse direction, based on the results obtained from the IVW model, no significant evidence was found to support a causal association between PD and delirium (IVW: OR: 1.078, 95%CI 0.960-1.204, P = 0.225). A sensitivity analysis verified the reliability of the results. CONCLUSION: According to the MR findings, a bidirectional causal relationship between delirium and PD is not observed. It is crucial to conduct further research in clinical practice to investigate the association between delirium and the risk of PD.

The association between adipokines and pulmonary diseases: a mendelian randomization study.

BACKGROUND: The role of adipokines in the development of lung diseases is significant, yet their specific relationship with different lung diseases remains unclear. METHODS: In our research, we analyzed genetic variations associated with adipokines and various lung conditions such as interstitial lung disease, chronic obstructive pulmonary disease, asthma, lung cancer, sleep apnea, pneumonia, and tuberculosis, using data from public genome-wide studies. We employed Mendelian randomization techniques, including inverse variance weighting, weighted median, and MR-Egger regression methods, and conducted sensitivity checks to validate our findings. RESULTS: A study using the FinnGen database, which included 198,955 participants, identified 13 SNPs associated with adiponectin. Notably, adiponectin was found to significantly reduce the risk of interstitial lung disease and idiopathic pulmonary fibrosis. However, little evidence was found to establish a direct cause-effect relationship between the six adipokines and several other lung conditions, including sarcoidosis, asthma, chronic obstructive pulmonary disease, lung cancer, tuberculosis, pneumonia, and sleep apnea syndrome. CONCLUSION: This study reveals a reverse link between adiponectin levels and the likelihood of interstitial lung disease, including idiopathic pulmonary fibrosis.

Ecological impact of surfactant Tween-80 on plankton: High-scale analyses reveal deeper hazards.

The ecological risks of surfactants have been largely neglected because of their low toxicity. Multiscale studies have indicated that even if a pollutant causes no acute toxicity in a test species, it may alter interspecific interactions and community characteristics through sublethal impacts on test organisms. Therefore, we investigated the lethal and sublethal responses of the plankton species Scenedesmus quadricauda, Chlorella vulgaris, and Daphnia magna, to surfactant Tween-80. Then, high-scale responses in grazer life-history traits and stability of the D. magna-larval damselfly system were further explored. The results showed that discernible adverse effects on the growth or survival of the three plankton species were evident only at exceptionally high concentrations (≥100 mg L-1). However, 10 mg L-1 of Tween-80 notably affected the MDA concentration in grazer species, simultaneously displaying a tendency to diminish grazer's heartbeat and swimming frequency. Furthermore, Tween-80 reduced the grazer reproductive capacity and increased its predation risk by larval damselflies, which ultimately jeopardized the stability of the D. magna-larval damselfly system at much lower concentrations (10-100 fold lower) than the individual-scale responses. This study provides evidence that high-scale traits are far more sensitive to Tween-80, compared with individual-scale traits for plankton organisms, suggesting that the ecological risks of Tween-80 demand careful reassessment. SYNOPSIS: The concentration of Tween-80 needed to induce changes in community characteristics is markedly lower than that needed to produce individual-scale consequences. Thus, high-scale analyses have broad implications for understanding the hazardous effects of surfactants compared with an individual-scale analysis.

Causal associations of sleep traits with cancer incidence and mortality.

To explore the correlation and causality between multidimensional sleep traits and pan-cancer incidence and mortality among patients with cancer. The multivariable Cox regression, linear and nonlinear Mendelian randomization (MR), and survival curve analyses were conducted to assess the impacts of chronotype, sleep duration, and insomnia symptoms on pan-cancer risk (N = 326,417 from United Kingdom Biobank) and mortality (N = 23,956 from United Kingdom Biobank). In the Cox regression, we observed a linear and J-shaped association of sleep duration with pan-cancer incidence and mortality among cancer patients respectively. In addition, there was a positive association of insomnia with pan-cancer incidence (HR, 1.03, 95% CI: 1.00-1.06, p = 0.035), all-cause mortality (HR, 1.17, 95% CI: 1.06-1.30, p = 0.002) and cancer mortality among cancer patients (HR, 1.25, 95% CI: 1.11-1.41, p < 0.001). In the linear MR, there was supporting evidence of positive associations between long sleep duration and pan-cancer incidence (OR, 1.41, 95% CI: 1.08-1.84, p = 0.012), and there was a positive association between long sleep duration and all-cause mortality in cancer patients (OR, 5.56, 95% CI: 3.15-9.82, p = 3.42E-09). Meanwhile, a strong association between insomnia and all-cause mortality in cancer patients (OR, 1.41, 95% CI: 1.27-1.56, p = 4.96E-11) was observed in the linear MR. These results suggest that long sleep duration and insomnia play important roles in pan-cancer risk and mortality among cancer patients. In addition to short sleep duration and insomnia, our findings highlight the effect of long sleep duration in cancer prevention and prognosis.

Using transfer learning-based causality extraction to mine latent factors for Sjögren's syndrome from biomedical literature.

Understanding causality is a longstanding goal across many different domains. Different articles, such as those published in medical journals, disseminate newly discovered knowledge that is often causal. In this paper, we use this intuition to build a model that leverages causal relations to unearth factors related to Sjögren's syndrome from biomedical literature. Sjögren's syndrome is an autoimmune disease affecting up to 3.1 million Americans. Due to the uncommon nature of the illness, symptoms across different specialties coupled with common symptoms of other autoimmune conditions such as rheumatoid arthritis, it is difficult for clinicians to diagnose the disease timely. Due to the lack of a dedicated dataset for causal relationships built from biomedical literature, we propose a transfer learning-based approach, where the relationship extraction model is trained on a wide variety of datasets. We conduct an empirical analysis of numerous neural network architectures and data transfer strategies for causal relation extraction. By conducting experiments with various contextual embedding layers and architectural components, we show that an ELECTRA-based sentence-level relation extraction model generalizes better than other architectures across varying web-based sources and annotation strategies. We use this empirical observation to create a pipeline for identifying causal sentences from literature text, extracting the causal relationships from causal sentences, and building a causal network consisting of latent factors related to Sjögren's syndrome. We show that our approach can retrieve such factors with high precision and recall values. Comparative experiments show that this approach leads to 25% improvement in retrieval F1-score compared to several state-of-the-art biomedical models, including BioBERT and Gram-CNN. We apply this model to a corpus of research articles related to Sjögren's syndrome collected from PubMed to create a causal network for Sjögren's syndrome. The proposed causal network for Sjögren's syndrome will potentially help clinicians with a holistic knowledge base for faster diagnosis.

Inferring the genetic relationship between brain imaging-derived phenotypes and risk of complex diseases by Mendelian randomization and genome-wide colocalization.

Observational studies consistently disclose brain imaging-derived phenotypes (IDPs) as critical markers for early diagnosis of both brain disorders and cardiovascular diseases. However, it remains unclear about the shared genetic landscape between brain IDPs and the risk of brain disorders and cardiovascular diseases, restricting the applications of potential diagnostic techniques through brain IDPs. Here, we reported genetic correlations and putative causal relationships between 921 brain IDPs, 20 brain disorders and six cardiovascular diseases by leveraging their large-scale genome-wide association study (GWAS) summary statistics. Applications of Mendelian randomization (MR) identified significant putative causal effects of multiple region-specific brain IDPs in relation to the increased risks for amyotrophic lateral sclerosis (ALS), major depressive disorder (MDD), autism spectrum disorder (ASD) and schizophrenia (SCZ). We also found brain IDPs specifically from temporal lobe as a putatively causal consequence of hypertension. The genome-wide colocalization analysis identified three genomic regions in which MDD, ASD and SCZ colocalized with the brain IDPs, and two novel SNPs to be associated with ASD, SCZ, and multiple brain IDPs. Furthermore, we identified a list of candidate genes involved in the shared genetics underlying pairs of brain IDPs and MDD, ASD, SCZ, ALS and hypertension. Our results provide novel insights into the genetic relationships between brain disorders and cardiovascular diseases and brain IDP, which may server as clues for using brain IDPs to predict risks of diseases.