scholarly journals Causal Association of Trauma With Subsequent Psychiatric Disorder: A Mendelian Randomization Study

2021 ◽  
Author(s):  
Dongqing Gu ◽  
Shan Ou ◽  
Guodong Liu
Keyword(s):  
Psychiatric Disorder ◽  
Mood Disorder ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Causal Association ◽  
Post Traumatic Stress ◽  
Mendelian Randomization Analysis ◽  
Increased Risk ◽  
Randomization Analysis

Abstract Objective Trauma has been proposed as a risk factor for the development of psychiatric disorder. This study aimed to determine the causal association between them. Methods Two-sample Mendelian randomization analyses were performed to estimate the causal association between trauma and psychiatric disorder. We obtained summary-level data for genetic variants associated with trauma and the corresponding association with psychiatric disorder from previous genome-wide association studies, and inverse variance weighted was used as the main method in our Mendelian randomization analysis. Results Genetically predisposed trauma was associated with an increased risk of psychiatric disorder (odds ratio [OR] = 1.02, 95% confidence interval [CI], 1.01–1.02,), mood disorder (OR = 1.01, 95% CI, 1.00-1.01) and depression (OR = 1.02, 95% CI, 1.01–1.02) in UK Biobank, as well as increased risk of mood disorder (OR = 1.23, 95% CI, 1.03–1.48), depression (OR = 1.10, 95% CI, 1.04–1.17), bipolar disorder (OR = 1.24, 95% CI, 1.04–1.49) and schizophrenia (OR = 1.47, 95% CI, 1.21–1.78) in data source from MR Base. However, Mendelian randomization evidence did not support an association between trauma and risk of post-traumatic stress disorder, anxiety disorder, sleep disorder, and eating disorder. Conclusions Findings from our Mendelian randomization analysis suggested that trauma might be causally associated with an increased risk of some common psychiatric disorder such as depression.

The impact of personality on the risk and survival of breast cancer: a Mendelian randomization analysis

2021 ◽  
pp. 1-7
Author(s):  
Li Ying ◽  
Songzan Chen ◽  
Ling Li ◽  
Zhijun Pan
Keyword(s):  
Breast Cancer ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Causative Role ◽  
Genome Wide Association Studies ◽  
Luminal A ◽  
Mendelian Randomization Analysis ◽  
Increased Risk ◽  
The Impact ◽  
Randomization Analysis

Abstract Background It has long been hypothesized that personality plays a causative role in incidence and outcome of breast cancer (BC), but epidemiological evidence of association between personality and BC is inconsistent. Method We used two-sample Mendelian randomization analysis to estimate the impact of personality on the risk and survival of BC. In total, 109 single nucleotide polymorphisms (SNPs) were utilized as instruments of neuroticism from a large-scale Genome-Wide Association Studies (GWAS), and five SNPs were utilized as instruments of extraversion from Genetic of Personality Consortium and 23andMe. Genetic association with the risk and survival of overall and individual subtype BC were obtained from the Breast Cancer Association Consortium. Result Neuroticism is significantly associated with the risk of overall BC [odds ratio (OR) 1.06; 95% confidence interval (CI) 1.01–1.11; p = 0.015] and the risk of luminal A BC (OR 1.09; 95% CI 1.03–1.16; p = 0.004). Extraversion is not associated with the risk of BC. None of neuroticism or extraversion is associated with the survival of BC. Conclusion Neuroticism was associated with a modest increased risk of BC and particularly luminal A BC.

scholarly journals Association of 25 hydroxyvitamin D concentration with risk of COVID-19: a Mendelian randomization study

2020 ◽  
Author(s):  
Di Liu ◽  
Qiuyue Tian ◽  
Jie Zhang ◽  
Haifeng Hou ◽  
Wei Wang ◽  
...  
Keyword(s):  
Causal Relationship ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Sensitivity Analyses ◽  
Genome Wide Association Studies ◽  
Causal Association ◽  
Hydroxyvitamin D ◽  
Increased Risk ◽  
25Ohd Concentration ◽  
25 Hydroxyvitamin D

Background In observational studies, 25 hydroxyvitamin D (25OHD) concentration has been associated with an increased risk of Coronavirus disease 2019 (COVID-19). However, it remains unclear whether this association is causal. Methods We performed a two-sample Mendelian randomization (MR) to explore the causal relationship between 25OHD concentration and COVID-19, using summary data from the genome-wide association studies (GWASs) and using 25OHD concentration-related SNPs as instrumental variables (IVs). Results MR analysis did not show any evidence of a causal association of 25OHD concentration with COVID-19 susceptibility and severity (odds ratio [OR]=1.136, 95% confidence interval [CI] 0.988-1.306, P=0.074; OR=0.889, 95% CI 0.549-1.439, P=0.632). Sensitivity analyses using different instruments and statistical models yielded similar findings, suggesting the robustness of the causal association. No obvious pleiotropy bias and heterogeneity were observed. Conclusion The MR analysis showed that there might be no linear causal relationship of 25OHD concentration with COVID-19 susceptibility and severity.

scholarly journals Association of 25 Hydroxyvitamin D Concentration with Risk of COVID-19: A Mendelian Randomization Study

2020 ◽  
Author(s):  
Di Liu ◽  
Qiuyue Tian ◽  
Jie Zhang ◽  
Haifeng Hou ◽  
Wei Wang ◽  
...  
Keyword(s):  
Causal Relationship ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Sensitivity Analyses ◽  
Genome Wide Association Studies ◽  
Causal Association ◽  
Hydroxyvitamin D ◽  
Increased Risk ◽  
25Ohd Concentration ◽  
25 Hydroxyvitamin D

Abstract Background: Coronavirus disease 2019 (COVID-19) has caused a large global pandemic. In observational studies, 25 hydroxyvitamin D (25OHD) concentration has been associated with an increased risk of Coronavirus disease 2019 (COVID-19). However, it remains unclear whether this association is causal.Methods: We performed a two-sample Mendelian randomization (MR) to explore the causal relationship between 25OHD concentration and COVID-19, using summary data from the genome-wide association studies (GWASs) and using 25OHD concentration-related SNPs as instrumental variables (IVs). Results: MR analysis did not show any evidence of a causal association of 25OHD concentration with COVID-19 susceptibility and severity (odds ratio [OR]=1.136, 95% confidence interval [CI] 0.988-1.306, P=0.074; OR=0.889, 95% CI 0.549-1.439, P=0.632). Sensitivity analyses using different instruments and statistical models yielded similar findings, suggesting the robustness of the causal association. No obvious pleiotropy bias and heterogeneity were observed.Conclusions: The MR analysis showed that there might be no linear causal relationship of 25OHD concentration with COVID-19 susceptibility and severity.

scholarly journals Gene Expression and RNA Splicing Imputation Identifies Novel Candidate Genes Associated with Osteoporosis

2020 ◽  
Vol 105 (12) ◽  
pp. e4742-e4757
Author(s):  
Yong Liu ◽  
Hui Shen ◽  
Jonathan Greenbaum ◽  
Anqi Liu ◽  
Kuan-Jui Su ◽  
...  
Keyword(s):  
Quantitative Trait Loci ◽  
Candidate Genes ◽  
Quantitative Trait ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Mineral Density ◽  
Mendelian Randomization Analysis ◽  
Trait Loci ◽  
Randomization Analysis

Abstract Context Though genome-wide association studies (GWASs) have identified hundreds of genetic variants associated with osteoporosis related traits, such as bone mineral density (BMD) and fracture, it remains a challenge to interpret their biological functions and underlying biological mechanisms. Objective Integrate diverse expression quantitative trait loci and splicing quantitative trait loci data with several powerful GWAS datasets to identify novel candidate genes associated with osteoporosis. Design, Setting, and Participants Here, we conducted a transcriptome-wide association study (TWAS) for total body BMD (TB-BMD) (n = 66 628 for discovery and 7697 for validation) and fracture (53 184 fracture cases and 373 611 controls for discovery and 37 857 cases and 227 116 controls for validation), respectively. We also conducted multi-SNP-based summarized mendelian randomization analysis to further validate our findings. Results In total, we detected 88 genes significantly associated with TB-BMD or fracture through expression or ribonucleic acid splicing. Summarized mendelian randomization analysis revealed that 78 of the significant genes may have potential causal effects on TB-BMD or fracture in at least 1 specific tissue. Among them, 64 genes have been reported in previous GWASs or TWASs for osteoporosis, such as ING3, CPED1, and WNT16, as well as 14 novel genes, such as DBF4B, GRN, TMUB2, and UNC93B1. Conclusions Overall, our findings provide novel insights into the pathogenesis mechanisms of osteoporosis and highlight the power of a TWAS to identify and prioritize potential causal genes.

scholarly journals Evaluating the effects of alcohol and tobacco use on cardiovascular disease using multivariable Mendelian randomization

2019 ◽  
Author(s):  
Daniel B. Rosoff ◽  
George Davey Smith ◽  
Nehal Mehta ◽  
Toni-Kim Clarke ◽  
Falk W. Lohoff
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Alcohol Use ◽  
Tobacco Use ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Density Lipoprotein ◽  
Genome Wide Association Studies ◽  
Cvd Risk ◽  
Increased Risk

ABSTRACTAlcohol and tobacco use, two major modifiable risk factors for cardiovascular disease (CVD), are often consumed together. Using large publicly available genome-wide association studies (results from > 940,000 participants), we conducted two-sample multivariable Mendelian randomization (MR) to simultaneously assess the independent effects of alcohol and tobacco use on CVD risk factors and events. We found genetic instruments associated with increased alcohol use, controlling for tobacco use, associated with increased high-density-lipoprotein-cholesterol (HDL-C), decreased triglycerides, but not with coronary heart disease (CHD), myocardial infarction (MI), nor stroke; and instruments for increased tobacco use, controlling for alcohol use, associated with decreased HDL-C, increased triglycerides, and increased risk of CHD and MI. Exploratory analysis found associations with HDL-C, LDL-C, and intermediate-density-lipoprotein metabolites. Consistency of results across complementary methods accommodating different MR assumptions strengthened causal inference, providing strong genetic evidence for the causal effects of modifiable lifestyle risk factors on CVD risk.

Daytime sleepiness, night sleep changes and ALS: a Mendelian randomization study

2020 ◽  
Author(s):  
Gan Zhang ◽  
Linjing Zhang ◽  
Tao Huang ◽  
Dongsheng Fan
Keyword(s):  
Sleep Duration ◽  
Daytime Sleepiness ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Sleep Efficiency ◽  
Genome Wide Association Studies ◽  
Night Sleep ◽  
Inverse Variance ◽  
Point Increase ◽  
Increased Risk

Abstract Background Observational studies have indicated that there is a high prevalence of daytime sleepiness and night sleep changes in amyotrophic lateral sclerosis (ALS). However, the actual relation between these symptoms and ALS remains unclear. We aimed to determine whether daytime sleepiness and night sleep changes have an effect on ALS. Methods We used 2-sample mendelian randomization to estimate the effects of daytime sleepiness, sleep efficiency, number of sleep episodes and sleep duration on ALS. Summary statistics we used was from resent and large genome-wide association studies on the traits we chosen (n = 85,670–452,071) and ALS (cases n = 20,806, controls n = 59,804). Inverse variance weighted method was used as the main method for assessing causality. Results A genetically predicted 1-point increase in the assessment of daytime sleepiness was significantly associated with an increased risk of ALS (inverse-variance-weighted (IVW) odds ratio = 2.70, 95% confidence interval (CI): 1.27–5.76; P = 0.010). ALS was not associated with a genetically predicted 1-SD increase in sleep efficiency (IVW 1.01, 0.64–1.58; P = 0.973), Number of sleep episodes (IVW 1.02, 0.80–1.30; P = 0.859) or sleep duration (IVW 1.00, 1.00–1.01; P = 0.250). Conclusions Our results provide novel evidence that daytime sleepiness causes an increase in the risk of ALS and indicate that daytime sleepiness may be inherent in preclinical and clinical ALS patients, rather than simply affected by potential influencing factors.

scholarly journals Software application profile: mrrobust—a tool for performing two-sample summary Mendelian randomization analyses

2018 ◽  
Vol 48 (3) ◽  
pp. 684-690 ◽  
Author(s):  
Wes Spiller ◽  
Neil M Davies ◽  
Tom M Palmer
Keyword(s):  
Mendelian Randomization ◽  
Association Studies ◽  
Estimation Methods ◽  
Genome Wide Association Studies ◽  
Software Application ◽  
Genome Wide ◽  
Inverse Variance ◽  
Randomization Analysis ◽  
Summary Data ◽  
Weighted Estimation

Abstract Motivation In recent years, Mendelian randomization analysis using summary data from genome-wide association studies has become a popular approach for investigating causal relationships in epidemiology. The mrrobust Stata package implements several of the recently developed methods. Implementation mrrobust is freely available as a Stata package. General features The package includes inverse variance weighted estimation, as well as a range of median, modal and MR-Egger estimation methods. Using mrrobust, plots can be constructed visualizing each estimate either individually or simultaneously. The package also provides statistics such as IGX2, which are useful in assessing attenuation bias in causal estimates. Availability The software is freely available from GitHub [https://raw.github.com/remlapmot/mrrobust/master/].

scholarly journals Causal Association between Serum Thyroid-Stimulating Hormone and Obesity: A Bidirectional Mendelian Randomization Study

2021 ◽  
Author(s):  
Xichang Wang ◽  
Xiaotong Gao ◽  
Yutong Han ◽  
Fan Zhang ◽  
Zheyu Lin ◽  
...  
Keyword(s):  
Mendelian Randomization ◽  
Association Studies ◽  
Epidemiological Studies ◽  
Thyroid Stimulating Hormone ◽  
Genome Wide Association Studies ◽  
Causal Association ◽  
Free Triiodothyronine ◽  
The Impact ◽  
Serum Tsh ◽  
Stimulating Hormone

Abstract Context The association between serum thyroid-stimulating hormone (TSH) and obesity traits has been investigated previously in several epidemiological studies. However, the underlying causal association has not been established. Objective To determine and analyze the causal association between serum TSH level and obesity-related traits (BMI and obesity). Design, Setting, Participants The latest genome-wide association studies (GWASs) on TSH, BMI and obesity were searched to obtain full statistics. Bidirectional two-sample Mendelian randomization (MR) was performed to explore the causal relationship between serum TSH and BMI and obesity. The inverse variance-weighted (IVW) and MR-Egger methods were used to combine the estimation for each SNP. Based on the preliminary MR results, free thyroxine (fT4) and free triiodothyronine (fT3) levels were also set as outcomes to further analyze the impact of BMI on them. Main Outcome Measures BMI and obesity were treated as the outcomes to evaluate the effect of serum TSH on them, and TSH was set as the outcome to estimate the effect of BMI and obesity on it. Results Both IVW and MR-Egger results indicated that genetically driven serum TSH did not causally lead to changes in BMI or obesity. Moreover, the IVW method showed that the TSH level could be significantly elevated by genetically predicted high BMI (β=0.038, se=0.013, p=0.004). In further MR analysis, the IVW method indicated that BMI could causally increase the fT3 (β=10.123, se=2.523, p<0.001) while not significantly affecting the fT4 level. Conclusion Together with fT3, TSH can be significantly elevated by an increase in genetically driven BMI.

scholarly journals Mendelian randomization analysis to characterize causal association between coronary artery disease and COVID-19

2020 ◽  
Author(s):  
Lang Wu ◽  
Jingjing Zhu ◽  
Chong Wu
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Observational Studies ◽  
Mendelian Randomization ◽  
Causal Association ◽  
Mendelian Randomization Analysis ◽  
Log Odds ◽  
Individual Decisions ◽  
Artery Disease ◽  
Randomization Analysis

AbstractObservational studies have suggested that having coronary artery disease increases the risk of Coronavirus disease 2019 (COVID-19) susceptibility and severity, but it remains unclear if this association is causal. Inferring causation is critical to facilitate the development of appropriate policies and/or individual decisions to reduce the incidence and burden of COVID-19. We applied Two-sample Mendelian randomization analysis and found that genetically predicted CAD was significantly associated with higher risk of COVID-19: the odds ratio was 1.29 (95% confidence interval 1.11 to 1.49; P = 0.001) per unit higher log odds of having CAD.

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