The Causal Role of Alcohol Use in Adolescent Externalizing and Internalizing Problems: A Mendelian Randomization Study

2017 ◽  
Vol 41 (11) ◽  
pp. 1953-1960 ◽  
Author(s):  
Miao Chao ◽  
Xinying Li ◽  
Matt McGue
Keyword(s):  
Alcohol Use ◽  
Internalizing Problems ◽  
Mendelian Randomization ◽  
Causal Role ◽  
Externalizing And Internalizing Problems

scholarly journals CD28 Genetic Variants Increase Susceptibility to Diabetic Kidney Disease in Chinese Patients with Type 2 Diabetes: A Cross-Sectional Case Control Study

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yangyang Li ◽  
Li Jin ◽  
Jing Yan ◽  
Hong Zhang ◽  
Rong Zhang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Mendelian Randomization ◽  
Costimulatory Molecule ◽  
Causal Role ◽  
Chinese Patients ◽  
Diabetic Kidney ◽  
Mendelian Randomization Analysis ◽  
Randomization Analysis

Few studies have illuminated the genetic role of T cell costimulatory molecule CD28/CD80/CTLA4 variants in diabetic kidney disease (DKD) susceptibility. We aimed to investigate the causal role of genetic polymorphisms in CD28/CD80/CTLA4 with DKD susceptibility in patients with T2DM. A total of 3253 patients with T2DM were recruited for genotyping: including 204 DKD patients and 371 controls in stage 1 and 819 DKD patients and 563 controls in stage 2; besides, 1296 T2DM patients were selected for the analysis of association between loci and DKD-related traits. A subset of 227 T2DM patients (118 patients with DKD and 109 patients without DKD) from the total population above were selected to assess serum soluble CD28 (sCD28) levels. Then, we performed a candidate gene association study to identify single-nucleotide polymorphisms (SNPs) associated with DKD susceptibility and further used those SNPs to perform Mendelian randomization analyses of serum sCD28 level and DKD susceptibility. Under additive genetic models, CD28-rs3116494 ( OR = 1.29 [95% CI 1.11, 1.51], P = 0.0011 ) and CD80-rs3850890 ( OR = 1.16 [95% CI 1.02, 1.31], P = 0.0283 ) were associated with DKD susceptibility adjusted for age, gender, body mass index (BMI), duration of diabetes, and HbA1c. CD28-rs3116494 was associated with serum sCD28 level ( β = 0.26 [95% CI 0.08, 0.44], P = 0.0043 ). The Mendelian randomization analysis showed that CD28-rs3116494 played a causal role in DKD by influencing serum sCD28 levels ( β = 1.15 [95% CI 0.46, 1.83], P = 0.0010 ). In conclusion, we identified that two novel SNPs, CD28-rs3116494 and CD80-rs3850890, were associated with DKD susceptibility. Using the Mendelian randomization analysis, our study provided evidence for a causal relationship between serum CD28 levels and DKD with T2DM in the Chinese population.

scholarly journals Body mass index and mortality in UK Biobank: revised estimates using Mendelian randomization

2018 ◽  
Author(s):  
Kaitlin H Wade ◽  
David Carslake ◽  
Naveed Sattar ◽  
George Davey Smith ◽  
Nicholas J Timpson
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Genotypic Variation ◽  
Lung Cancer Mortality ◽  
Causal Role ◽  
Uk Biobank ◽  
All Cause Mortality

AbstractObjectiveObtain estimates of the causal relationship between different levels of body mass index (BMI) and mortality.MethodsMendelian randomization (MR) was conducted using genotypic variation reliably associated with BMI to test the causal effect of increasing BMI on all-cause and cause-specific mortality in participants of White British ancestry in UK Biobank.ResultsMR analyses supported existing evidence for a causal association between higher levels of BMI and greater risk of all-cause mortality (hazard ratio (HR) per 1kg/m2: 1.02; 95% CI: 0.97,1.06) and mortality from cardiovascular diseases (HR: 1.12; 95% CI: 1.02, 1.23), specifically coronary heart disease (HR: 1.19; 95% CI: 1.05, 1.35) and those other than stroke/aortic aneurysm (HR: 1.13; 95% CI: 0.93, 1.38), stomach cancer (HR: 1.30; 95% CI: 0.91, 1.86) and oesophageal cancer (HR: 1.08; 95% CI: 0.84, 1.38), and with decreased risk of lung cancer mortality (HR: 0.97; 95% CI: 0.84, 1.11). Sex-stratified analyses supported a causal role of higher BMI in increasing the risk of mortality from bladder cancer in males and other causes in females, but in decreasing the risk of respiratory disease mortality in males. The characteristic J-shaped observational association between BMI and mortality was visible with MR analyses but with a smaller value of BMI at which mortality risk was lowest and apparently flatter over a larger range of BMI.ConclusionResults support a causal role of higher BMI in increasing the risk of all-cause mortality and mortality from other causes. However, studies with greater numbers of deaths are needed to confirm the current findings.

scholarly journals Obesity and atypical depression symptoms: findings from Mendelian randomization in two European cohorts

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giorgio Pistis ◽  
Yuri Milaneschi ◽  
Caroline L. Vandeleur ◽  
Aurélie M. Lasserre ◽  
Brenda W.J.H. Penninx ◽  
...  
Keyword(s):  
Mendelian Randomization ◽  
Causal Effect ◽  
Fat Distribution ◽  
The Body ◽  
Causal Role ◽  
Depression Symptoms ◽  
Specific Symptom ◽  
Atypical Depression ◽  
Atypical Symptoms

AbstractStudies considering the causal role of body mass index (BMI) for the predisposition of major depressive disorder (MDD) based on a Mendelian Randomization (MR) approach have shown contradictory results. These inconsistent findings may be attributable to the heterogeneity of MDD; in fact, several studies have documented associations between BMI and mainly the atypical subtype of MDD. Using a MR approach, we investigated the potential causal role of obesity in both the atypical subtype and its five specific symptoms assessed according to the Statistical Manual of Mental Disorders (DSM), in two large European cohorts, CoLaus|PsyCoLaus (n = 3350, 1461 cases and 1889 controls) and NESDA|NTR (n = 4139, 1182 cases and 2957 controls). We first tested general obesity measured by BMI and then the body fat distribution measured by waist-to-hip ratio (WHR). Results suggested that BMI is potentially causally related to the symptom increase in appetite, for which inverse variance weighted, simple median and weighted median MR regression estimated slopes were 0.68 (SE = 0.23, p = 0.004), 0.77 (SE = 0.37, p = 0.036), and 1.11 (SE = 0.39, p = 0.004). No causal effect of BMI or WHR was found on the risk of the atypical subtype or for any of the other atypical symptoms. Our findings show that higher obesity is likely causal for the specific symptom of increase in appetite in depressed participants and reiterate the need to study depression at the granular level of its symptoms to further elucidate potential causal relationships and gain additional insight into its biological underpinnings.

scholarly journals A phenome-wide multi-directional Mendelian randomization analysis of atrial fibrillation

2020 ◽  
Author(s):  
Qin Wang ◽  
Tom G Richardson ◽  
Eleanor Sanderson ◽  
Mika Ala-Korpela ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Body Mass Index ◽  
Coronary Artery ◽  
Mendelian Randomization ◽  
Causal Role ◽  
Coronary Artery Diseases ◽  
Genetic Liability

AbstractBackgroundThe prevalence of atrial fibrillation (AF) is increasing with an aging worldwide population, yet a comprehensive understanding of its causes and consequences remains limited.ObjectivesTo assess the causes and consequences of AF via a multi-directional Mendelian randomization (MR) analysis scanning thousands of traits in a hypothesis-free approach.MethodsWe used publicly available GWAS data centralised and harmonised by the IEU open GWAS database. We assessed the potential causal role of 5048 exposures on risk of AF and the causal role of genetic liability to AF on 10,308 outcomes via two-sample MR analysis. Multivariable MR analysis was further conducted to explore the comparative role of identified risk factors.ResultsMR analysis suggested that 55 out of 5048 exposure traits, including four proteins, play a causal role in AF (P < 1e-5 allowing for multiple comparisons). Multivariable analysis suggested that higher body mass index, height, systolic blood pressure as well as genetic liability to coronary artery diseases independently cause AF. Three out of the four proteins (DUSP13, TNFSF12 and IL6R) had a drug prioritising score for atrial fibrillation of 0.26, 0.38 and 0.88, respectively (values closer to 1 indicating stronger evidence of the protein as a potential drug target). Genetic liability to AF was linked to a higher risk of cardioembolic ischemic stroke.ConclusionsBody mass index, height, systolic blood pressure and genetic liability to coronary artery diseases are independent causal risk factors for AF. Several proteins including DUSP13, IL-6R and TNFSF12 may represent therapeutic potential for preventing AF.

scholarly journals The Relation between Maternal Personality and Internalizing/Externalizing Behaviors: Mediating Role of Maternal Alexithymia, Children’s Alexithymia and Emotional Regulation

2021 ◽  
Author(s):  
Ghazal Davodi-Boroujerd ◽  
Imaneh Abasi ◽  
Abbas Masjedi Arani ◽  
Maryam Aslzaker
Keyword(s):  
Emotion Regulation ◽  
Internalizing Problems ◽  
Externalizing Behaviors ◽  
Mediating Role ◽  
Maternal Personality ◽  
Internalizing And Externalizing Behaviors ◽  
Externalizing And Internalizing Problems ◽  
Children's Emotion ◽  
Internalizing And Externalizing

Objective: Although many studies have investigated the effect of maternal personality on internalizing and externalizing behaviors of a child, the role of both mother and child’s emotional mechanisms in these behaviors is little explored. The present study was focused on the relationship between the mother’s personality, and internalizing and externalizing behaviors of children with the mediating role of children’s alexithymia, mother’s alexithymia, and children’s emotion regulation (ER). Method: 162 mothers and elementary school-aged children were recruited regarding their demographics and completed the NEO personality inventory, Child behavior checklist, Toronto alexithymia scale, Children’s alexithymia measure, and Children’s emotion regulation checklist. Data were analyzed using SPSS (ver.23), and AMOS (ver.23). Results: Structural equations modeling demonstrated an acceptable model fit to data (CMIN/DF = 1.233, RSME = 0.038, GFI = 0.962). Mother’s alexithymia predicted internalizing problems whereas it didn’t predict externalizing problems in children. Also, the bootstrap results indicated that the mother and children’s alexithymia and children’s ER had mediating roles between mother’s personality and externalizing and internalizing problems. Conclusion: The present results demonstrated that mother’s personality can indirectly, through mother and children’s alexithymia and children’s ER act as an important factor in development of mental problems. In other words, findings indicated that children’s emotional development is not a one-way road, but it is a mutual process that involves both the mother and the child.

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