Negative Causal Effect Research Articles

Causal effect of gallstone disease on the risk of coronary heart disease or acute myocardial infarction: a Mendelian randomization study

Gallstone disease (GSD) is thought to be associated with the risk of coronary heart disease (CHD) or acute myocardial infarction (AMI), which may be due to abnormal cholesterol metabolism. We used multiple Mendelian randomization (MR) methods based on publicly available genome-wide association study data to assess whether this association is genetically causal and to search for loci driving causality. Pooled data for GSD were obtained from FinnGen Biobank and Biobank Japan, while CHD and AMI were obtained as pooled data from the CARDIoGRAMplusC4D consortium. In this MR study, we found a significant negative causal effect of genetic susceptibility to GSD on AMI in the Finnish population, but no causal effect was found on CHD. This causal effect was not confounded by reverse causality and the same findings were obtained in the Japanese population. Furthermore, the negative causal effect of GSD on AMI risk may be driven by the rs4245791-regulated ABCG5/8 protein. In conclusion, the results of this MR study support a negative causal effect of GSD on AMI and suggest that rs4245791 is the causal driver locus of this effect, which provides new ideas and evidence for the prevention and etiologic study of AMI in patients with GSD.

Association between sarcopenia-related traits and cardiovascular diseases: a bi-directional Mendelian randomization study.

The two geriatric diseases, sarcopenia and cardiovascular disease (CVD), often coexist, yet the causal relationship is unclear. However, few studies focus on the effect of muscle mass on CVD. This comprehensive study is dedicated to unearthing the potential connection between sarcopenia-related traits and CVD at the genetic level. A two-sample bi-directional Mendelian randomization (MR) study was conducted. In the first stage, we performed MR analysis regarding coronary heart disease (CHD), stroke, and myocardial infarction (MI) as exposure factors to reveal their effect on appendicular lean mass (ALM) and hand grip strength. In the second stage, we reverse the position of exposures and outcomes. The inverse variance weighted (IVW) method was used as the primary approach to reveal the potential causation between the exposure and outcome. The results of the IVW method revealed a negative causal effect of ALM on CHD (OR = 0.848, 95% CI = 0.804 to 0.894, p = 8.200E-10), stroke (OR = 0.931, 95% CI = 0.890 to 0.975, p = 2.220E-03), and MI (OR = 0.810, 95% CI = 0.694 to 0.901, p = 1.266E-13). Additionally, the left-hand grip strength is a significant protective factor for CHD (OR = 0.737, 95% CI = 0.601 to 0.904, p = 3.353E-03) and MI (OR = 0.631, 95% CI = 0.515 to 0.765, p = 2.575E-06), but is not causally linked to the stroke (OR = 0.971, 95% CI =0.829 to 1.139, p = 0.720). Meanwhile, the same conclusion about the effect of right-hand grip strength on CHD (OR = 0.681, 95% CI = 0.558 to 0.832, p = 1.702E-05), MI (OR = 0.634, 95% CI = 0.518 to 0.776, p = 9.069E-06), and stroke (OR = 1.041, 95% CI = 0.896 to 1.209, p = 0.604) was obtained. However, no significant causal effect of CVD (CHD, stroke, MI) on sarcopenia-related traits (ALM, handgrip strength) was found. There is a unidirectional causal relationship between sarcopenia and CVD. The loss of muscle mass and strength has a significant causal role in promoting the occurrence and development of CVD, providing a reference for the prevention and treatment of comorbidities in older people.

Causal Effects of Gut Microbiota on Sleep-Related Phenotypes: A Two-Sample Mendelian Randomization Study.

Increasing evidence suggests a correlation between changes in the composition of gut microbiota and sleep-related phenotypes. However, it remains uncertain whether these associations indicate a causal relationship. The genome-wide association study summary statistics data of gut microbiota (n = 18,340) was downloaded from the MiBioGen consortium and the data of sleep-related phenotypes were derived from the UK Biobank, the Medical Research Council-Integrative Epidemiology Unit, Jones SE, the FinnGen consortium. To test and estimate the causal effect of gut microbiota on sleep traits, a two-sample Mendelian randomization (MR) approach using multiple methods was conducted. A series of sensitive analyses, such as horizontal pleiotropy analysis, heterogeneity test, MR Steiger directionality test and "leave-one-out" analysis as well as reverse MR analysis, were conducted to assess the robustness of MR results. The genus Anaerofilum has a negative causal effect on getting up in the morning (odd ratio = 0.977, 95% confidence interval: 0.965-0.988, p = 7.28 × 10-5). A higher abundance of order Enterobacteriales and family Enterobacteriaceae contributed to becoming an "evening person". Six and two taxa were causally associated with longer and shorter sleep duration, respectively. Specifically, two SCFA-produced genera including Lachnospiraceae UCG004 (odd ratio = 1.029, 95% confidence interval = 1.012-1.046, p = 6.11 × 10-4) and Odoribacter contribute to extending sleep duration. Two obesity-related genera such as Ruminococcus torques (odd ratio = 1.024, 95% confidence interval: 1.011-1.036, p = 1.74 × 10-4) and Senegalimassilia were found to be increased and decreased risk of snoring, respectively. In addition, we found two risk taxa of insomnia such as the order Selenomonadales and one of its classes called Negativicutes. All of the sensitive analysis and reverse MR analysis results indicated that our MR results were robust. Our study revealed the causal effect of gut microbiota on sleep and identified causal risk and protective taxa for chronotype, sleep duration, snoring and insomnia, which has the potential to provide new perspectives for future mechanistic and clinical investigations of microbiota-mediated sleep abnormal patterns and provide clues for developing potential microbiota-based intervention strategies for sleep-related conditions.

The effects of unsaturated fatty acids on psoriasis: A two-sample Mendelian randomization study.

Unsaturated fatty acids have been reported to be associated with the risk of psoriasis. However, the causal relationship between them remains unclear This study aimed to explore the causal relationship between unsaturated FAs and psoriasis. Firstly, we obtained genome-wide association study (GWAS) data for psoriasis from the FINNGEN database (number of cases = 4510, number of controls = 212,242) and different FA levels (number of samples = 114,999) from the IEU OpenGWAS Project. Secondly, the genetic correlation coefficient was calculated using linkage disequilibrium fractional regression. Thirdly, a two-sample Mendelian randomization (MR) analysis was performed using independent instrumental variables (p < 5 × 10-8) to determine the direction of randomization. Finally, expression quantitative trait loci (eQTL)-related analyses of common single nucleotide polymorphisms (SNPs) were carried out to explore the potential molecular mechanisms of unsaturated FAs affecting psoriasis. We found that an increase in the ratio of monounsaturated fatty acids (MUFAs) to total fatty acids could increase the risk of psoriasis (inverse-variance weighted [IVW], adjusted odds ratio [OR] = 1.175; adjusted 95% confidence interval [CI] = 1.045-1.321; adjusted p = .007). However, an increase in the ratio of polyunsaturated fatty acids (PUFAa) to total fatty acids could decrease the risk of psoriasis (IVW, adjusted OR = 0.754; adjusted 95% CI = 0.631-0.901; adjusted p = .002). Moreover, an increase in the ratio of PUFAs to MUFAs could decrease the risk of psoriasis (IVW, adjusted OR = 0.823; adjusted 95% CI = 0.715-0.948; adjusted p = .007). The heterogeneity of data was eliminated, and pleiotropy was not detected. There was no statistical difference in the MR analysis of other fatty acids indices with psoriasis. Further, no statistically significant evidence was found to verify a causal relationship between psoriasis and fatty acid levels in reverse MR. Functional enrichment analysis showed that these eQTL related to common SNPs were mainly involved in organic ion transport, choline metabolism, and the expression of key metabolic factors mediated by PKA, ChREBP, and PP2A. Our study indicated that the ratio of MUFAs to total fatty acids had a positive causal effect on psoriasis, while the ratio of PUFAs to total fatty acids and the ratio of PUFAs to MUFAs had a negative causal effect on psoriasis. Moreover, PKA-, PP2A-, and ChREBP-mediated activation of metabolic factors may play an important role in this process.

An investigation of exchange rate, exchange rate volatility and FDI nexus in a gravity model approach

ABSTRACT This study assesses the significance of exchange rate and exchange rate volatility in the bilateral inflows of FDI using a gravity model, based on a sample of 40 countries over the period 2001 to 2019. This analysis is also specifically concerned with the estimation challenges which revolve around the validity of the log-linear transformation of the gravity equation in the potential presence of heteroscedasticity and zero FDI observations. The various alternative estimation techniques, all validate the fact that exchange rate volatility has a negative impact on the bilateral inflows of FDI whereas exchange rate depreciation has a positive and significant coefficient. On the other hand, the variables GDP-host and GDP-Home are positive and significant justifying that the host and home countries’ economic sizes remain factual elements in attracting FDI. The models’ estimates also interestingly validate the fact that geographical distance and tax level have a sizeable negative influence on the bilateral inflow of FDI. Besides, the significance of the dummy variable common language confirms a negative causal effect of a communication barrier between the local workers and foreign investors.

Deciphering the causal relationship between blood pressure and regional white matter integrity: A two-sample Mendelian randomization study.

Elevated arterial blood pressure (BP) is a common risk factor for cerebrovascular and cardiovascular diseases, but no causal relationship has been established between BP and cerebral white matter (WM) integrity. In this study, we performed a two-sample Mendelian randomization (MR) analysis with individual-level data by defining two nonoverlapping sets of European ancestry individuals (genetics-exposure set: N = 203,111; mean age = 56.71 years, genetics-outcome set: N = 16,156; mean age = 54.61 years) from UK Biobank to evaluate the causal effects of BP on regional WM integrity, measured by fractional anisotropy of diffusion tensor imaging. Two BP traits: systolic and diastolic blood pressure were used as exposures. Genetic variant was carefully selected as instrumental variable (IV) under the MR analysis assumptions. We existing large-scale genome-wide association study summary data for validation. The main method used was a generalized version of inverse-variance weight method while other MR methods were also applied for consistent findings. Two additional MR analyses were performed to exclude the possibility of reverse causality. We found significantly negative causal effects (FDR-adjusted p < .05; every 10 mmHg increase in BP leads to a decrease in FA value by .4% ~ 2%) of BP traits on a union set of 17 WM tracts, including brain regions related to cognitive function and memory. Our study extended the previous findings of association to causation for regional WM integrity, providing insights into the pathological processes of elevated BP that might chronically alter the brain microstructure in different regions.

Gut microbiota and Sjögren's syndrome: a two-sample Mendelian randomization study.

The link between the gut microbiota (GM) and Sjögren's Syndrome (SS) is well-established and apparent. Whether GM is causally associated with SS is uncertain. The MiBioGen consortium's biggest available genome-wide association study (GWAS) meta-analysis (n=13,266) was used as the basis for a two-sample Mendelian randomization study (TSMR). The causal relationship between GM and SS was investigated using the inverse variance weighted, MR-Egger, weighted median, weighted model, MR-PRESSO, and simple model methods. In order to measure the heterogeneity of instrumental variables (IVs), Cochran's Q statistics were utilized. The results showed that genus Fusicatenibacter (odds ratio (OR) = 1.418, 95% confidence interval (CI), 1.072-1.874, P = 0.0143) and genus Ruminiclostridium9 (OR = 1.677, 95% CI, 1.050-2.678, P = 0.0306) were positively correlated with the risk of SS and family Porphyromonadaceae (OR = 0.651, 95% CI, 0.427-0.994, P = 0.0466), genus Subdoligranulum (OR = 0.685, 95% CI, 0.497-0.945, P = 0.0211), genus Butyricicoccus (OR = 0.674, 95% CI, 0.470-0.967, P = 0.0319) and genus Lachnospiraceae (OR = 0.750, 95% CI, 0.585-0.961, P = 0.0229) were negatively correlated with SS risk using the inverse variance weighted (IVW) technique. Furthermore, four GM related genes: ARAP3, NMUR1, TEC and SIRPD were significant causally with SS after FDR correction (FDR<0.05). This study provides evidence for either positive or negative causal effects of GM composition and its related genes on SS risk. We want to provide novel approaches for continued GM and SS-related research and therapy by elucidating the genetic relationship between GM and SS.

The effects of coagulation factors on the risk of endometriosis: a Mendelian randomization study

BackgroundEndometriosis is recognized as a complex gynecological disorder that can cause severe pain and infertility, affecting 6–10% of all reproductive-aged women. Endometriosis is a condition in which endometrial tissue, which normally lines the inside of the uterus, deposits in other tissues. The etiology and pathogenesis of endometriosis remain ambiguous. Despite debates, it is generally agreed that endometriosis is a chronic inflammatory disease, and patients with endometriosis appear to be in a hypercoagulable state. The coagulation system plays important roles in hemostasis and inflammatory responses. Therefore, the purpose of this study is to use publicly available GWAS summary statistics to examine the causal relationship between coagulation factors and the risk of endometriosis.MethodsTo investigate the causal relationship between coagulation factors and the risk of endometriosis, a two-sample Mendelian randomization (MR) analytic framework was used. A series of quality control procedures were followed in order to select eligible instrumental variables that were strongly associated with the exposures (vWF, ADAMTS13, aPTT, FVIII, FXI, FVII, FX, ETP, PAI-1, protein C, and plasmin). Two independent cohorts of European ancestry with endometriosis GWAS summary statistics were used: UK Biobank (4354 cases and 217,500 controls) and FinnGen (8288 cases and 68,969 controls). We conducted MR analyses separately in the UK Biobank and FinnGen, followed by a meta-analysis. The Cochran’s Q test, MR-Egger intercept test, and leave-one-out sensitivity analyses were used to assess the heterogeneities, horizontal pleiotropy, and stabilities of SNPs in endometriosis.ResultsOur two-sample MR analysis of 11 coagulation factors in the UK Biobank suggested a reliable causal effect of genetically predicted plasma ADAMTS13 level on decreased endometriosis risk. A negative causal effect of ADAMTS13 and a positive causal effect of vWF on endometriosis were observed in the FinnGen. In the meta-analysis, the causal associations remained significant with a strong effect size. The MR analyses also identified potential causal effects of ADAMTS13 and vWF on different sub-phenotypes of endometrioses.ConclusionsOur MR analysis based on GWAS data from large-scale population studies demonstrated the causal associations between ADAMTS13/vWF and the risk of endometriosis. These findings suggest that these coagulation factors are involved in the development of endometriosis and may represent potential therapeutic targets for the management of this complex disease.

A network causal relationship between type-1 diabetes mellitus, 25-hydroxyvitamin D level and systemic lupus erythematosus: Mendelian randomization study.

Observational studies have suggested a relationship between type-1 diabetes mellitus (T1DM) and systemic lupus erythematosus (SLE). In both autoimmunities, 25-hydroxyvitamin D (25-OHD) deficiency is common. However, the causality between T1DM, 25-OHD level and SLE remains largely unknown. Independent genetic variants associated with T1DM, 25-OHD level, and SLE from the largest genome-wide association studies were used to conduct two-sample bidirectional Mendelian randomization (BIMR) and two-step Mendelian randomization (MR) analysis to estimate causal relationship between T1DM, 25-OHD level and SLE, and further multivariable Mendelian randomization (MVMR) was used to verify direct causality of T1DM and 25-OHD level on SLE. A series of sensitivity analysis as validation of primary MR results were performed. Consistent with the results of BIMR, there was strong evidence for a direct causal effect of T1DM on the risk of SLE (ORMVMR-IVW = 1.249, 95% CI = 1.148-1.360, PMVMR-IVW = 1.25×10-5), and 25-OHD level was negatively associated with the risk of SLE (ORMVMR-IVW = 0.305, 95% CI = 0.109-0.857, PMVMR-IVW = 0.031). We also observed a negative causal effect of T1DM on 25-OHD level (ORBIMR-IVW = 0.995, 95% CI = 0.991-0.999, PBIMR-IVW = 0.030) while the causal effect of 25-OHD level on the risk of T1DM did not exist (PBIMR-IVW = 0.106). In BIMR analysis, there was no evidence for causal effects of SLE on the risk of T1DM and 25-OHD level (PBIMR-IVW > 0.05, respectively). Our MR analysis suggested that there was a network causal relationship between T1DM, 25-OHD level and SLE. T1DM and 25-OHD level both have causal associations with the risk of SLE, and 25-OHD level could be a mediator in the causality of T1DM and SLE.

P075 Mendelian randomization studies of lifestyle-related risk factors for osteoarthritis: a PRISMA review and meta-analysis

Abstract Background/Aims Risk factors for osteoarthritis (OA) often exert effects over protracted time-courses. Mendelian randomization (MR) studies therefore have an advantage over conventional observational studies when studying the causal effect of long-term lifestyle-related risk factors on OA. However, given the heterogeneous design of existing MR studies on OA, the reported causal estimates of these effects remain inconsistent, thus obscuring the true extent of the biological effects of OA lifestyle-risk factors. Methods We conducted a PRISMA systematic review and specifically included MR studies that investigated the causal effect between lifestyle-related risk factors and OA, where causal estimates for various lifestyle factors were pooled for meta-analysis. Quality of studies was assessed according to STROBE-MR guidelines. Results A total of 1576 studies were evaluated and 23 were included. Overall, the studies included were of high quality and had a low risk of bias. Our meta-analysis demonstrates the positive causal effect of BMI (ORIVW-random effects 1.49 [1.23-1.80]) and negative causal effects of serum calcium (ORIVW-random effects 0.69 [0.57-0.83]) and LDL levels (ORIVW-random effects 0.93 [0.90-0.96]) on OA. Conclusion Despite the heterogeneous designs and estimates of causal effects provided by various MR studies, our meta-analysis suggests that lifestyle-related risk factors in the form of BMI, serum calcium, and LDL have true biological effects on the development of OA. Disclosure J. Ho: None. C. Mak: None.

Does export liberalization cause the agglomeration of pollution? Evidence from China

This paper investigates the impact of export liberalization on the geographic concentration of water pollution. Data shows that water pollution emissions are unevenly distributed across regions in China. Using China's accession to the World Trade Organization (WTO) as the exogenous shock, we identify a negative causal effect of export liberalization on the agglomeration of water pollution across regions in China. It suggests that relatively more water pollution is discharged in those previously low-pollution regions after export liberalization. We confirm this with data on regional relative pollution emissions. Further decomposition shows that it is the intensive margin (average pollution emission) rather than the extensive margin (number of polluting firms) that drives the deglomeration of water pollution emissions within the liberalized industry.

Shared genetic architecture between attention-deficit/hyperactivity disorder and lifespan

There is evidence linking ADHD to a reduced life expectancy. The mortality rate in individuals with ADHD is twice that of the general population and it is associated with several factors, such as unhealthy lifestyle behaviors, social adversity, and mental health problems that may in turn increase mortality rates. Since ADHD and lifespan are heritable, we used data from genome-wide association studies (GWAS) of ADHD and parental lifespan, as proxy of individual lifespan, to estimate their genetic correlation, identify genetic loci jointly associated with both phenotypes and assess causality. We confirmed a negative genetic correlation between ADHD and parental lifespan (rg = −0.36, P = 1.41e−16). Nineteen independent loci were jointly associated with both ADHD and parental lifespan, with most of the alleles that increased the risk for ADHD being associated with shorter lifespan. Fifteen loci were novel for ADHD and two were already present in the original GWAS on parental lifespan. Mendelian randomization analyses pointed towards a negative causal effect of ADHD liability on lifespan (P = 1.54e−06; Beta = −0.07), although these results were not confirmed by all sensitivity analyses performed, and further evidence is required. The present study provides the first evidence of a common genetic background between ADHD and lifespan, which may play a role in the reported effect of ADHD on premature mortality risk. These results are consistent with previous epidemiological data describing reduced lifespan in mental disorders and support that ADHD is an important health condition that could negatively affect future life outcomes.

Effect of Seclusion on Mental Health Status in Hospitalized Psychiatric Populations: A Trial Emulation using Observational Data.

The use of coercive practices, i.e., interventions against a person's will, is controversial. Recent observational studies highlighted their potential detrimental effects on patients' mental health, but this topic remains understudied. This study investigated the effect of a common coercive practice, seclusion (i.e., being locked in a closed room), on mental health using a trial emulation of observational data to allow causal inference. We used data from 1200 psychiatric inpatients, classified as being either secluded or non-secluded during their hospital stay. Inverse probability of treatment weighting was used to emulate the random assignment to the intervention. The primary outcome was the Health of the Nations Outcome Scales (HoNOS). The secondary outcome was the first item of the HoNOS, which focuses on overactive, aggressive, disruptive, or agitated behavior. Both outcomes were assessed at hospital discharge. There was a significant effect of seclusion with increases in both total HoNOS score (p = .002) and item 1 of the HoNOS (p = .01). Seclusion may have a negative causal effect of patients' mental health status and should therefore be avoided in mental health care settings. Training efforts should raise the awareness of the medical staff about potential adverse effects instead of therapeutic benefits.

Impact of COVID-19 on online grocery shopping discussion and behavior reflected from Google Trends and geotagged tweets

People express opinions, make connections, and disseminate information on social media platforms. We considered grocery-related tweets as a proxy for grocery shopping behaviors or intentions. We collected data from January 2019 to January 2022, representing three typical times of the normal period before the COVID-19 pandemic, the outbreak period, and the widespread period. We obtained grocery-related geotagged tweets using a search term index based on the top 10 grocery chains in the US and compiled Google Trends online grocery shopping data. We performed a topic modeling analysis using the Latent Dirichlet Allocation (LDA), and verified that most of the collected tweets were related to grocery-shopping demands or experiences. Temporal and geographical analyses were applied to investigate when and where people talked more about groceries, and how COVID-19 affected them. The results show that the pandemic has been gradually changing people’s daily shopping concerns and behaviors, which have become more spread throughout the week since the pandemic began. Under the causal impact of COVID-19, people first experienced panic buying groceries followed by pandemic fatigue a year later. The normalized tweet counts show a decrease of 40% since the pandemic began, and the negative causal effect can be considered statistically significant (p-value = 0.001). The variation in the quantity of grocery-related tweets also reflects geographic diversity in grocery concerns. We found that people in non-farm areas with less population and relatively lower levels of educational attainment tend to act more sensitively to the evolution of the pandemic. Utilizing the COVID-19 death cases and consumer price index (CPI) for food at home as background information, we proposed an understanding of the pandemic’s impact on online grocery shopping by assembling, geovisualizing, and analyzing the evolution of online grocery behaviors and discussion on social media before and during the pandemic.

Utility of video analysis and expert modelling for technique development in novice sport climbers: A randomized controlled study

Sport climbing is a multifaceted sport that also requires appropriate techniques to optimize movements. As augmented feedback is known to facilitate motor learning, we investigated the utility of adding video analysis and expert modelling to standardized verbal feedback for the acquisition of three climbing-specific techniques (drop knee, heel hook and high step). Twenty-six novice climbers (12 women) completed two testing sessions before and after a training intervention that consisted of three coached climbing sessions targeting the three techniques. Participants were randomly assigned to a control group, which solely received standardized verbal feedback or an experimental group that additionally received standardized video analysis and expert modelling using the Dartfish tablet application. Video recordings were subsequently evaluated by two climbing experts on a 7-point scale. The expert scores were higher in the experimental than in the control group for the high step (causal total effect (CTE) 0.38, 95% confidence interval (CI) [0.06, 0.68]). Improvements for the drop knee (CTE = 0.12, 95% CI [−0.24, 0.48]) and heel hook (CTE = −0.05, 95% CI [−0.42, 0.31]) were similar in both groups. For the drop knee, we, however, observed a positive causal direct effect (CDE = 0.38, 95% CI [0.07, 0.68]), which was comparable to that observed for the high step but also a negative causal mediator effect via the perceived difficulty (CME = −0.26, 95% CI [−0.51, −0.04]). Compared to verbal feedback solely, the addition of video analysis and expert modelling might facilitate the acquisition of certain climbing techniques, such as high step, in novice climbers.

Hot hand or choking under pressure – Evidence from professional basketball

AbstractThis paper examines the existence of a hot hand and whether performing in front of a supportive audience creates a psychological pressure, which may impair performance. Using the task of free throwing in basketball competitions involving National Basketball Association (NBA) regular season and playoff games, I find strong evidence of a hot hand and a negative causal effect of the spectators on the probability of a successful shoot. The results support the hot hand fallacy and are in line with the hypothesis of choking under pressure when performing skill‐based tasks. Furthermore, contrary to what would be expected given the evidence in favor of a choking phenomenon, the effect of star players is insignificant. The hot hand effects for stars and non‐stars are the same in direction. Finally, efforts increase the performance, and the influence of hot hands and choking are not different between home and away shootings.

Abstract B003: Causal effect of type II diabetes on prostate cancer in the East Asian population: A two-sample Mendelian randomization study

Abstract Type II diabetes, a metabolic disease, and prostate cancer are prevalent diseases in the elderly population. Whether type II diabetes has an association with prostate cancer has not been thoroughly studied. Limited research has been performed from a perspective of genetic level, especially among non-European populations. In this study, we used a two-sample Mendelian randomization (MR) approach to evaluate the causal effect between type II diabetes as an exposure and prostate cancer as an outcome in the East Asian population. For type II diabetes, we used 174 risk loci identified in a meta-analysis of 77,418 cases and 356,122 controls from 23 East Asian Genome-wide Association Studies (GWAS). For prostate cancer, summary statistics were extracted from the GWAS from BioBank Japan using 5,408 cases and 103,939 controls. We performed two-sample Mendelian randomization with the inverse variance weighted method while using MR Egger and weighted median methods as sensitivity analysis. For type II diabetes risk SNPs not directly present in the prostate cancer GWAS, we identified proxy SNPs in linkage disequilibrium (LD, r2 &amp;gt; 0.8) using the 1000 genome project. We used P-value &amp;lt; 0.05 as a threshold to determine statistical significance. Based on 152 out of 174 SNPs of type II diabetes in the East Asian population, we found that type II diabetes had a significant negative causal effect on prostate cancer [Odds Ratio (OR) = 0.76, 95% Confidence Interval (CI): 0.76 - 0.89, P = 2.26 x 10-6]. Results from sensitivity analysis using other weighting methods provided similar results. In conclusion, we observed an inverse relationship between type II diabetes and prostate cancer among the East Asian population. Patients with diabetes may have a lower risk of prostate cancer due to a reduced level of insulin and testosterone. To validate this association, further research is needed on those hormones and prostate cancer risk at the metabolic level. Citation Format: Zhongyi Guo. Causal effect of type II diabetes on prostate cancer in the East Asian population: A two-sample Mendelian randomization study [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr B003.

Financial reform and haze pollution: A quasi-natural experiment of the financial reform pilot zones in China

Financial reform becomes a new tool for environmental governance because it can indirectly affect the environment by promoting economic and financial agglomeration and technological innovation. Despite China's aggressive financial reform pilot (FRP) policy since 2012, little is known about whether and how such policy affects haze pollution (HP). We exploit geographic and temporal variations in China's FRP policy and compile a dataset covering 284 cities over the period from 2003 to 2019. Employing a difference-in-differences (DID) approach, we document that China's FRP policy has a negative causal effect on HP in the pilot cities. The estimates obtained from an instrumental variable constructed by religious temples also support the haze-abatement effect of such policy. This effect is largely driven by advances in technological innovation and increases in economic agglomeration, while financial agglomeration is proven to have little effect. Finally, our estimate is particularly pronounced in cities with high levels of economic development, financial development and technological innovation, and that in large-sized and non-mineral resourced cities. Overall, our findings shed light on the importance of financial reform in environmental governance in a developing country.

Causal associations of tea intake with COVID-19 infection and severity.

Tea ingredients can effectively inhibit SARS-CoV-2 infection at adequate concentrations. It is not known whether tea intake could impact the susceptibility to COVID-19 or its severity. We aimed to evaluate the causal effects of tea intake on COVID-19 outcomes. We performed Mendelian randomization (MR) analyses to assess the causal associations between tea intake (N = 441,279) and three COVID-19 outcomes, including SARS-CoV-2 infection (122,616 cases and 2,475,240 controls), hospitalized COVID-19 (32,519 cases and 2,062,805 controls), and critical COVID-19 (13,769 cases and 1,072,442 controls). The MR analyses indicated that genetic propensity for tea consumption conferred a negative causal effect on the risk of SARS-CoV-2 infection (OR: 0.87, 95% confidence interval (CI): 0.78-0.97, P = 0.015). No causal effects on hospitalized COVID-19 (0.84, 0.64-1.10, P = 0.201) or critical COVID-19 (0.73, 0.51-1.03, P = 0.074) were detected. Our study revealed that tea intake could decrease the risk of SARS-CoV-2 infection, highlighting the potential preventive effect of tea consumption on COVID-19 transmission.

High blood pressure mediated the effect of fasting insulin level on nonalcoholic fatty liver disease risk: A Mendelian randomization study.

The interactions between fasting insulin levels, high blood pressure and nonalcoholic fatty liver disease (NAFLD) are still unclear. We examined the causal mechanisms between these three cardiometabolic traits using Mendelian randomization (MR) approach by utilizing genetic instruments. Three different genome-wide association studies resources of European ancestry were utilized for the present study. Two-sample MRs were used to assess causal effects between fasting insulin levels, high blood pressure and NAFLD. Multivariate MR was used to calculate the mediating effect. The inverse variance-weighted method was used as the main analysis method. Our study confirmed a causal effect of fasting insulin levels (IVW-OR = 9.54, P = 0.001) and high blood pressure (IVW-OR = 3.926, P = 0.005) on NAFLD risk. And fasting insulin level was positively casually associated with high blood pressure risk (IVW-OR = 1.170, P < 0.001). However, the impact of high blood pressure on fasting insulin levels was still uncertain because of the presence of horizontal pleiotropy. Reverse MR showed NAFLD had a positive correlation with fasting insulin levels (IVW-OR = 1.010, P < 0.001) and a negative causal effect on high blood pressure risk (IVW-OR = 0.997, P = 0.037). Combined the multivariate MR result revealed high blood pressure partially mediated the contribution of fasting insulin level to NAFLD risk (proportion mediated: 9.091%). Our study suggests there is a bidirectional causal relationship between fasting insulin levels and NAFLD. High blood pressure seems to play a mediating role in the development of NAFLD caused by changes in fasting insulin levels. However, it is uncertain whether high blood pressure is a mediator between NAFLD and the risk of fasting insulin level.