Bidirectional Causal Effects Research Articles

Triangulated evidence provides no support for bidirectional causal pathways between diet/physical activity and depression/anxiety.

Previous studies (various designs) present contradicting insights on the potential causal effects of diet/physical activity on depression/anxiety (and vice versa). To clarify this, we employed a triangulation framework including three methods with unique strengths/limitations/potential biases to examine possible bidirectional causal effects of diet/physical activity on depression/anxiety. Study 1: 3-wave longitudinal study (n=9,276 Dutch University students). Using random intercept cross-lagged panel models to study temporal associations. Study 2: cross-sectional study (n=341 monozygotic and n=415 dizygotic Australian adult twin pairs). Using a co-twin control design to separate genetic/environmental confounding. Study 3: Mendelian randomization utilizing data (European ancestry) from genome-wide association studies (n varied between 17,310 and 447,401). Using genetic variants as instrumental variables to study causal inference. Study 1 did not provide support for bidirectional causal effects between diet/physical activity and symptoms of depression/anxiety. Study 2 did provide support for causal effects between fruit/vegetable intake and symptoms of depression/anxiety, mixed support for causal effects between physical activity and symptoms of depression/anxiety, and no support for causal effects between sweet/savoury snack intake and symptoms of depression/anxiety. Study 3 provides support for a causal effect from increased fruit intake to the increased likelihood of anxiety. No support was found for other pathways. Adjusting the analyses including diet for physical activity (and vice versa) did not change the conclusions in any study. Triangulating the evidence across the studies did not provide compelling support for causal effects of diet/physical activity on depression/anxiety or vice versa.

Examining the effects of biofield therapy through simultaneous assessment of electrophysiological and cellular outcomes

In this case study, a self-described biofield therapy (BT) practitioner (participant) took part in multiple (n = 60) treatment and control (non-treatment) sessions under double-blind conditions. During the treatment phases, the participant provided BT treatment at a distance of about 12 inches from the cells, alternating with rest phases where no such efforts were made. Human pancreatic cancer cell activity was assessed using three markers – cytoskeleton changes (tubulin and β-actin) and Ca2+ uptake. The study examined changes in the participant’s physiological parameters including electroencephalogram (EEG) and heart rate measures during the treatment of: (1) live cells and (2) either dead cells or medium only with no cells (control group). Changes in cellular outcomes and if there was an association between the participant’s physiological parameters and cellular outcomes were examined. The experimental setup was a 2 × 2 design, contrasting cell type (live vs. control) against session type (treatment vs. non-treatment). Parallel sham-treated control cells were examined for changes in the cell parameters over time while controlling for the presence of a person in front of the cells mimicking the distance and movements of the participant. The participant’s physiological data, including 64-channel EEG and heart rate, were continuously monitored throughout these sessions. We observed significant (p < 0.01) spectral changes in the participant’s EEG during BT treatment in all frequency bands of interest, as well as in heart rate variability (HRV) (RMSSD measure; p < 0.01). We also observed significant differences in beta and gamma EEG and HRV (pNN50 measure) when the participant treated live but not control cells (p = 0.02). However, no interaction between treatment and cell type (live vs. dead cells/medium-no cells) was observed. We observed Ca2+ uptake increased over time during both BT and sham treatment, but the increase was significantly less for the BT group relative to the sham-treatment controls (p = 0.03). When using Granger causality to assess causal directional associations between cell markers and participant’s physiological parameters, EEG measurements showed significant bidirectional causal effects with cell metrics, especially β-actin and intracellular Ca2+ levels (p < 0.000001). These outcomes suggest a complex relationship between physiological responses and cellular effects during BT treatment sessions. Given the study’s limitations, follow-up investigations are warranted.

A focusing framework for testing bi-directional causal effects in Mendelian randomization

A focusing framework for testing bi-directional causal effects in Mendelian randomization

Art for health's sake or health for art's sake: Disentangling the bidirectional relationships between arts engagement and mental health.

Increasing evidence links arts engagement with mental health, but the directionality of the link remains unclear. Applying a novel approach to causal inference, we used nonrecursive instrumental variable models to analyze two waves of data from the United Kingdom Household Longitudinal Study (n = 17,927). Our findings reveal bidirectional causal relationships between arts engagement (arts participation, cultural attendance, and heritage visits) and mental health (GHQ-12 mental distress and SF-12 Mental Component Summary mental well-being). After adjusting for time 1 measures and identifying confounders, cultural attendance and heritage visits were reciprocally associated with mental distress and mental well-being, while arts participation was only reciprocally associated with mental well-being. The bidirectional effects between arts engagement and mental health are modest but clearly demonstrated not only from mental health to arts but also from arts to mental health. Our findings indicate that previous evidence of an association between arts engagement and mental health is due to bidirectional causal effects. Interventions that boost arts participation, cultural attendance, and heritage visits may help break the negative feedback loop and enhance mental health.

Genomic Correlation, Shared Loci, and Causal Relationship Between Bullous Pemphigoid and Atopic Dermatitis: A Large-Scale Genome-Wide Cross-Trait Analysis.

Bullous pemphigoid (BP) and atopic dermatitis (AD) are currently thought to be tightly related, yet studies of the mechanisms of co-morbidities are lacking. We obtained GWAS data for BP (N = 376,274) and AD (N = 796,661) from the Finnish Genetic Research Program dataset and the UK Biobank, separately. Then, the following four analyses were performed: (1) cross-trait linkage disequilibrium score regression (LDSC) to assess the genetic correlation between BP and AD, (2) cross-phenotype association analysis (CPASSOC) to identify multiple effector loci shared by BP and AD, (3) transcriptome-wide association study (TWAS) to determine whether their cross-organizational expression patterns share genes with a common biological mechanism of relevance, and (4) bidirectional Mendelian randomization (MR) analysis to assess bidirectional causal effects of BP and AD. We found a positive genetic association between BP and AD (rg = 0.5476, p = 0.0495) as well as identified four pleiotropic loci and 59 common genes affecting BP and AD. Bidirectional MR analysis suggested that BP promotes the risk of AD. We revealed a genetic link between BP and AD, which is associated with biological pleiotropy and causality. Awareness of the association between BP and AD helps dermatologists manage patients with these illnesses.

A convergent cross‐mapping approach for unveiling congestion spatial causality in urban traffic networks

AbstractSpatial causality in urban traffic networks explores how events or conditions in one location affect those in another. Unveiling congestion spatial causality is crucial for identifying congestion‐inducing bottlenecks in traffic networks and offering valuable insights for traffic network management and control. This study introduces the traffic‐convergent‐cross‐mapping (T‐CCM) method, a state‐space‐reconstruction approach from the dynamic system perspective, to identify causality among roads within urban traffic networks using time series data. Simultaneously, it effectively addresses the intricate challenges of uncertainty and interdependency among sensors caused by traffic flow dynamics. Empirical findings from real‐world (PeMS‐Bay area) traffic speed data validate the effectiveness of the T‐CCM method in detecting causality. This study reveals bidirectional causal effects between downstream and upstream roads in short‐term congestion generation and dissipation periods, which can pinpoint congestion origins and inform quick traffic management response. Furthermore, it elucidates the long‐term causality impacts between distant roads, particularly with regard to traveler choices and road land use attributes, guiding infrastructure investment and public transit improvements.

Differential white blood cell count and epigenetic clocks: a bidirectional Mendelian randomization study

BackgroundHuman aging and white blood cell (WBC) count are complex traits influenced by multiple genetic factors. Predictors of chronological age have been developed using epigenetic clocks. However, the bidirectional causal effects between epigenetic clocks and WBC count have not been fully examined.MethodsThis study employed Mendelian randomization (MR) to analyze summary statistics from four epigenetic clocks involving 34,710 participants, alongside data from the Blood Cell Consortium encompassing 563,946 individuals. We primarily explored bidirectional causal relationships using the random-effects inverse-variance weighted method, supplemented by additional MR methods for comprehensive analysis. Additionally, multivariate MR was applied to investigate independent effects of WBC count on epigenetic age acceleration.ResultsIn the two-sample univariate MR (UVMR) analysis, we observed that a decrease in lymphocyte count markedly accelerated aging according to the PhenoAge, GrimAge, and HannumAge metrics (all P < 0.01, β < 0), though it did not affect Intrinsic Epigenetic Age Acceleration (IEAA). Conversely, an increase in neutrophil count significantly elevated PhenoAge levels (β: 0.38; 95% CI 0.14, 0.61; P = 1.65E−03 < 0.01). Reverse MR revealed no significant causal impacts of epigenetic clocks on overall WBC counts. Furthermore, in multivariate MR, the impact of lymphocyte counts on epigenetic aging metrics remained statistically significant. We also identified a marked causal association between neutrophil counts and PhenoAge, GrimAge, and HannumAge, with respective results showing strong associations (PhenoAge β: 0.78; 95% CI 0.47, 1.09; P = 8.26E−07; GrimAge β: 0.55; 95% CI 0.31, 0.79; P = 5.50E−06; HannumAge β: 0.42; 95% CI 0.18, 0.67; P = 6.30E−04). Likewise, eosinophil cell count demonstrated significant association with HannumAge (β: 0.33; 95% CI 0.13, 0.53; P = 1.43E−03 < 0.01).ConclusionThese findings demonstrated that within WBCs, lymphocyte and neutrophil counts exert irreversible and independent causal effects on the acceleration of PhenoAge, GrimAge, and HannumAge. Our findings highlight the critical role of WBCs in influencing epigenetic clocks and underscore the importance of considering immune parameters when interpreting epigenetic age.

Exploring the Relationship Between Sporadic Creutzfeldt-Jakob Disease and Gut Microbiota Through a Mendelian Randomization Study.

Observational studies have shown gut microbiota changes in sporadic Creutzfeldt-Jakob disease patients, but the causal relationship remains unknown. We aimed to determine any causal links between gut microbiota and this prion disease. Using Mendelian randomization analysis, we examined the causal relationship between gut microbiota composition and sporadic Creutzfeldt-Jakob disease. Data on gut microbiota (N = 18,340) and disease cases (5208) were obtained. Various analysis methods were used, including inverse variance weighted, Mendelian randomization-Egger, weighted median, simple mode, and weighted mode. In addition, MR-PRESSO was used to evaluate horizontal pleiotropy and detect outliers. Pleiotropy and heterogeneity were assessed, and reverse analysis was conducted. Negative associations were found between sporadic Creutzfeldt-Jakob disease and family Defluviitaleaceae, family Ruminococcaceae, genus Butyricicoccus, genus Desulfovibrio, and genus Eubacterium nodatum. Genus Lachnospiraceae UCG010 showed a positive correlation. Reverse analysis indicated genetic associations between the disease and decreased levels of family Peptococcaceae, genus Faecalibacterium, and genus Phascolarctobacterium, as well as increased levels of genus Butyrivibrio. No pleiotropy, heterogeneity, outliers, or weak instrument bias were observed. This study revealed bidirectional causal effects between specific gut microbiota components and sporadic Creutzfeldt-Jakob disease. Certain components demonstrated inhibitory effects on disease pathogenesis, while others were positively associated with the disease. Modulating gut microbiota may provide new insights into prion disease therapies. Further research is needed to clarify mechanisms and explore treatments for sporadic Creutzfeldt-Jakob disease.

Gut microbiome and major depressive disorder: insights from two-sample Mendelian randomization

BackgroundExisting evidence suggests that alterations in the gut microbiome are closely associated with major depressive disorder (MDD). We aimed to reveal the causal relationships between MDD and various microbial taxa in the gut.MethodsWe used the two-sample Mendelian randomization (TSMR) to explore the bidirectional causal effects between gut microbiota and MDD. The genome-wide association studies summary results of gut microbiota were obtained from two large consortia, the MibioGen consortium and the Dutch Microbiome Project, which we analyzed separately.ResultsOur TSMR analysis identified 10 gut bacterial taxa that were protective against MDD, including phylum Actinobacteria, order Clostridiales, and family Bifidobacteriaceae (OR: 0.96 ∼ 0.98). Ten taxa were associated with an increased risk of MDD, including phyla Firmicutes and Proteobacteria, class Actinobacteria, and genus Alistipes (OR: 1.01 ∼ 1.09). On the other hand, MDD may decrease the abundance of 12 taxa, including phyla Actinobacteria and Firmicutes, families Bifidobacteriaceae and Defluviitaleaceae (OR: 0.63 ∼ 0.88). MDD may increase the abundance of 8 taxa, including phylum Bacteroidetes, genera Parabacteroides, and Bacteroides (OR: 1.12 ∼ 1.43).ConclusionsOur study supports that there are mutual causal relationships between certain gut microbiota and the development of MDD suggesting that gut microbiota may be targeted in the treatment of MDD.

Bidirectional brain-body interactions during natural story listening

Narratives can synchronize neural and physiological signals between individuals, but the relationship between these signals, and the underlying mechanism, is unclear. We hypothesized a top-down effect of cognition on arousal and predicted that auditory narratives will drive not only brain signals but also peripheral physiological signals. We find that auditory narratives entrained gaze variation, saccade initiation, pupil size, and heart rate. This is consistent with a top-down effect of cognition on autonomic function. We also hypothesized a bottom-up effect, whereby autonomic physiology affects arousal. Controlled breathing affected pupil size, and heart rate was entrained by controlled saccades. Additionally, fluctuations in heart rate preceded fluctuations of pupil size and brain signals. Gaze variation, pupil size, and heart rate were all associated with anterior-central brain signals. Together, these results suggest bidirectional causal effects between peripheral autonomic function and central brain circuits involved in the control of arousal.

Mendelian Randomization of Blood Metabolites Suggests Circulating Glutamine Protects Against Late-Onset Alzheimer's Disease.

Late-onset Alzheimer's disease (LOAD) represents a growing health burden. Previous studies suggest that blood metabolite levels influence risk of LOAD. We used a genetics-based study design which may overcome limitations of other epidemiological studies to assess the influence of metabolite levels on LOAD risk. We applied Mendelian randomization (MR) to evaluate bi-directional causal effects using summary statistics from the largest genome-wide association studies (GWAS) of 249 blood metabolites (n = 115,082) and GWAS of LOAD (ncase = 21,982, ncontrol = 41,944). MR analysis of metabolites as exposures revealed a negative association of genetically-predicted glutamine levels with LOAD (Odds Ratio (OR) = 0.83, 95% CI = 0.73, 0.92) that was consistent in multiple sensitivity analyses. We also identified a positive association of genetically-predicted free cholesterol levels in small LDL (OR = 1.79, 95% CI = 1.36, 2.22) on LOAD. Using genetically-predicted LOAD as the exposure, we identified associations with phospholipids to total lipids ratio in large LDL (OR = 0.96, 95% CI = 0.94, 0.98), but not with glutamine, suggesting that the relationship between glutamine and LOAD is unidirectional. Our findings support previous evidence that higher circulating levels of glutamine may be a target for protection against LOAD.

Approaches to estimate bidirectional causal effects using Mendelian randomization with application to body mass index and fasting glucose.

Mendelian randomization (MR) is an epidemiological framework using genetic variants as instrumental variables (IVs) to examine the causal effect of exposures on outcomes. Statistical methods based on unidirectional MR (UMR) are widely used to estimate the causal effects of exposures on outcomes in observational studies. To estimate the bidirectional causal effects between two phenotypes, investigators have naively applied UMR methods separately in each direction. However, bidirectional causal effects between two phenotypes create a feedback loop that biases the estimation when UMR methods are naively applied. To overcome this limitation, we proposed two novel approaches to estimate bidirectional causal effects using MR: BiRatio and BiLIML, which are extensions of the standard ratio, and limited information maximum likelihood (LIML) methods, respectively. We compared the performance of the two proposed methods with the naive application of UMR methods through extensive simulations of several scenarios involving varying numbers of strong and weak IVs. Our simulation results showed that when multiple strong IVs are used, the proposed methods provided accurate bidirectional causal effect estimation in terms of median absolute bias and relative median absolute bias. Furthermore, compared to the BiRatio method, the BiLIML method provided a more accurate estimation of causal effects when weak IVs were used. Therefore, based on our simulations, we concluded that the BiLIML should be used for bidirectional causal effect estimation. We applied the proposed methods to investigate the potential bidirectional relationship between obesity and diabetes using the data from the Multi-Ethnic Study of Atherosclerosis cohort. We used body mass index (BMI) and fasting glucose (FG) as measures of obesity and type 2 diabetes, respectively. Our results from the BiLIML method revealed the bidirectional causal relationship between BMI and FG in across all racial populations. Specifically, in the White/Caucasian population, a 1 kg/m2 increase in BMI increased FG by 0.70 mg/dL (95% confidence interval [CI]: 0.3517-1.0489; p = 8.43×10-5), and 1 mg/dL increase in FG increased BMI by 0.10 kg/m2 (95% CI: 0.0441-0.1640; p = 6.79×10-4). Our study provides novel findings and quantifies the effect sizes of the bidirectional causal relationship between BMI and FG. However, further studies are needed to understand the biological and functional mechanisms underlying the bidirectional pathway.

Bidirectional Relationship Between Depression and Frailty in Older Adults aged 70-84 years using Random Intercepts Cross-Lagged Panel Analysis

Purpose: Depression and frailty are common health problems that occur separately or simultaneously in later life. The two syndromes are correlated, but they need to be distinguished to promote successful aging. Previous studies have examined the reciprocal relationship between depression and frailty, but there are limitations in the methods or statistical analysis. This study aims to confirm the potential prospective bidirectional and causal relationship between depression and frailty. Methods: We used data from 887 older adults aged 70 to 84 from the Korean Frailty and Aging Cohort Study (KFACS) in 2016, 2018, and 2020 (3 waves). We separated the within-individual process from the stable between-individual differences using the random intercepts cross-lagged panel model. Results: Significant bidirectional causal effects were observed in 2 paths. Older adults with higher depression than their within-person average at T1 had a higher risk of frailty at T2 (β=.22, p=.008). Subsequently, older adults with higher-than-average frailty scores at T2 showed higher depression at T3 (β=.14, p=.010). Autoregressive effects were only significant from T2 to T3 for both constructs (Depression: β=.16, p=.044; Frailty: β=.13, p=.028). At the between-person level, the correlation was significant between the random intercepts between depression and frailty (β=.47, p&lt;.001). Conclusions: We find that depressed older adults have an increased risk of frailty, which contributes to the onset of depression and the maintenance of frailty. Therefore, interventions for each condition may prevent the entry and worsening of the other condition, as well as prevent comorbidity.

Assessing the relationship between gut microbiota and endometriosis: a bidirectional two-sample mendelian randomization analysis

BackgroundAn increasing body of observational studies have indicated an association between gut microbiota and endometriosis. However, the causal relationship between them is not yet clear. In this study, we employed Mendelian randomization method to investigate the causal relationship between 211 gut microbiota taxa and endometriosis.MethodsIndependent genetic loci significantly associated with the relative abundance of 211 gut microbiota taxa, based on predefined thresholds, were extracted as instrumental variables. The primary analytical approach employed was the IVW method. Effect estimates were assessed primarily using the odds ratio and 95% confidence intervals. Supplementary analyses were conducted using MR-Egger regression, the weighted median method, the simple mode and the weighted mode method to complement the IVW results. In addition, we conducted tests for heterogeneity, horizontal pleiotropy, sensitivity analysis, and MR Steiger to assess the robustness of the results and the strength of the causal relationships.ResultsBased on the IVW method, we found that the family Prevotellaceae, genus Anaerotruncus, genus Olsenella, genus Oscillospira, and order Bacillales were identified as risk factors for endometriosis, while class Melainabacteria and genus Eubacterium ruminantium group were protective factors. Additionally, no causal relationship was observed between endometriosis and gut microbiota. Heterogeneity tests, pleiotropy tests, and leave-one-out sensitivity analyses did not detect any significant heterogeneity or pleiotropic effects.ConclusionsOur MR study has provided evidence supporting a potential causal relationship between gut microbiota and endometriosis, and it suggests the absence of bidirectional causal effects. These findings could potentially offer new insights for the development of novel strategies for the prevention and treatment of endometriosis.

Mendelian randomization and Bayesian model averaging of autoimmune diseases and Long COVID.

Following COVID-19, reports suggest Long COVID and autoimmune diseases (AIDs) in infected individuals. However, bidirectional causal effects between Long COVID and AIDs, which may help to prevent diseases, have not been fully investigated. Summary-level data from genome-wide association studies (GWAS) of Long COVID (N = 52615) and AIDs including inflammatory bowel disease (IBD) (N = 377277), Crohn's disease (CD) (N = 361508), ulcerative colitis (UC) (N = 376564), etc. were employed. Bidirectional causal effects were gauged between AIDs and Long COVID by exploiting Mendelian randomization (MR) and Bayesian model averaging (BMA). The evidence of causal effects of IBD (OR = 1.06, 95% CI = 1.00-1.11, p = 3.13E-02), CD (OR = 1.10, 95% CI = 1.01-1.19, p = 2.21E-02) and UC (OR = 1.08, 95% CI = 1.03-1.13, p = 2.35E-03) on Long COVID was found. In MR-BMA, UC was estimated as the highest-ranked causal factor (MIP = 0.488, MACE = 0.035), followed by IBD and CD. This MR study found that IBD, CD and UC had causal effects on Long COVID, which suggests a necessity to screen high-risk populations.

Rheumatoid arthritis and gastroesophageal reflux disease: a bidirectional and multivariable two-sample Mendelian randomization study.

Aims/hypothesis: The association between gastroesophageal reflux disease (GERD) and rheumatoid arthritis (RA) has been reported by many observational studies in the Asian population. This study aimed to examine the bidirectional causal effects between GERD and RA by two-sample Mendelian randomization (MR) analyses using genetic evidence. Methods: Two-sample Mendelian randomization analyses were performed to determine the causal effect of GERD (129,080 cases vs. 602,604 control participants) on RA (6,236 cases vs. 147,221 control participants) and RA on GERD, respectively. The inverse-variance weighted (IVW) method was used as the primary analysis. Weighted median and MR-Egger regression were taken as supplementary analyses. Cochran's Q test evaluated the heterogeneity. Horizontal pleiotropy was detected by estimating the intercept term of MR-Egger regression. Furthermore, multivariable MR analyses were performed to exclude the influence of confounding factors, including the years of schooling, BMI, and time spent watching television, between GERD and RA. Result: Both univariate MR (UVMR) and multivariable MR (MVMR) provided valid evidence that RA was causally and positively influenced by GERD (UVMR: OR = 1.49, 95% CI = 1.25-1.76, p = 6.18*10-6; MVMR: OR = 1.69, 95% CI = 1.24-2.31, p = 8.62*10-4), whereas GERD was not influenced by RA (UVMR: OR = 1.03, 95% CI = 1.00-1.06, p = 0.042; MVMR: OR = 1.04, 95% CI = 1.00-1.07, p = 0.0271). Conclusion: Our comprehensive bidirectional MR analysis found that for the European population, GERD can induce the occurrence of RA (OR = 1.69, p < 0.00125), whereas RA only has no significant influence on GERD. In particular, patients with GERD are suffering a 69% increased risk of RA occurrence, which means GERD is a substantial risk factor for RA.

Distilling causality between physical activity traits and obesity via Mendelian randomization

BackgroundWhether obesity is a cause or consequence of low physical activity levels and more sedentary time has not yet been fully elucidated. Better instrumental variables and a more thorough consideration of potential confounding variables that may influence the causal inference between physical activity and obesity are needed.MethodsLeveraging results from our recent genome-wide association study for leisure time moderate-to-vigorous intensity (MV) physical activity and screen time, we here disentangle the causal relationships between physical activity, sedentary behavior, education—defined by years of schooling—and body mass index (BMI), using multiple univariable and multivariable Mendelian Randomization (MR) approaches.ResultsUnivariable MR analyses suggest bidirectional causal effects of physical activity and sedentary behavior with BMI. However, multivariable MR analyses that take years of schooling into account suggest that more MV physical activity causes a lower BMI, and a higher BMI causes more screen time, but not vice versa. In addition, more years of schooling causes higher levels of MV physical activity, less screen time, and lower BMI.ConclusionsIn conclusion, our results highlight the beneficial effect of education on improved health and suggest that a more physically active lifestyle leads to lower BMI, while sedentary behavior is a consequence of higher BMI.

Enhanced causal effect of ecosystem photosynthesis on respiration during heatwaves.

Because of global warming, Earth's ecosystems have been experiencing more frequent and severe heatwaves. Heatwaves are expected to tip terrestrial carbon sequestration by elevating ecosystem respiration and suppressing gross primary productivity (GPP). Here, using the convergent cross-mapping technique, this study detected positive bidirectional causal effects between GPP and respiration in two unprecedented European heatwaves. Heatwaves enhanced the causal effect strength of GPP on respiration rather than respiration on GPP across 40 site-years of observations. Further analyses and global simulations revealed spatial heterogeneity in the heatwave response of the causal link strength between GPP and respiration, which was jointly driven by the local climate and vegetation properties. However, the causal effect strength of GPP on respiration showed considerable uncertainties in CMIP6 models. This study reveals an enhanced causal link strength between GPP and respiration during heatwaves, shedding light on improving projections for terrestrial carbon sink dynamics under future climate extremes.

Ethnic disparities in bidirectional causal effects between serum uric acid concentrations and kidney function: Trans-ethnic Mendelian randomization study

IntroductionResearchers have investigated the causal effect between serum uric acid (SUA) concentrations and kidney function for decades, but studies produced inconsistent results. This study aimed to clarify the bidirectional causal effects between SUA concentrations and kidney function and to explore the potential ethnic disparities by conducting a trans-ethnic Mendelian randomization study in European, African, and Asian ancestries. Materials and methodsThe summary-level data for this study were obtained from the Global Urate Genetics Consortium, CKDGen Consortium, UK Biobank, and Japan Biobank for different outcomes and exposures, respectively. The traits of kidney function were estimated glomerular filtration rate from serum creatinine (eGFRcr), estimated glomerular filtration rate from cystatin C (eGFRcys), and blood urea nitrogen (BUN). Using the multiplicative random-effects inverse variance weighting mode, our primary analysis produced robust results despite heterogeneity. Additionally, we performed the Mendelian randomization pleiotropy residual sum and outlier test to eliminate the horizontal pleiotropy and obtain accurate results. ResultsOur findings revealed that elevated SUA concentrations had causal effects on declined eGFRcys, BUN, and a diagnosis of chronic kidney disease in European ancestries and eGFRcr in Asian ancestries. Additionally, the causal effects of declined eGFRcr and elevated BUN concentrations on elevated SUA concentrations were observed in both European and Asian ancestries. However, no bidirectional causal effect was found between SUA concentrations and eGFRcr among African ancestries. ConclusionsThis trans-ethnic Mendelian randomization study confirmed the bidirectional causal effects between SUA concentrations and kidney function and highlighted the importance of considering ethnic disparities in clinical treatments.

Causality and interdependencies among sustainable development goals: assessing the nexus of agriculture, environment, and finance development.

This study examines the causal relationships and interdependencies among three dimensions of sustainable development goals (SDGs) in Africa: environmental factors, agricultural production (for societal aspects), and finance development (for economic aspects). The study focuses on three regions, the whole SSA (Sub-Saharan Africa, excluding the high-income countries), West-Central Africa (W-CA), and South and East Africa (S-EA), and uses data from 1970 to 2018. It uses vector error correction model (VECM), impulse response function (IRF), and analysis of causality direction methods. The findings indicate bidirectional causal effects among the three SDG dimensions in Africa. Finance development factors influence both environmental and agricultural factors, while agro-production factors significantly affect both finance development and environmental factors. This study concludes that bidirectional causal effects exist within these dimensions, confirming their interdependencies and emphasizing the need for integrating these dimensions into African sustainable development goals. Recommendations include incorporating green aspects in financing development plans and establishing regulatory authorities to effectively coordinate and control these sustainable dimensions at both the Sub-Saharan Africa and state levels, ensuring impactful greenhouse and sustainable agriculture development for sustainable food production.