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 Genetic Contribution of Endometriosis to the Risk of Developing Hormone-Related Cancers

2021 ◽  
Vol 22 (11) ◽  
pp. 6083
Author(s):  
Aintzane Rueda-Martínez ◽  
Aiara Garitazelaia ◽  
Ariadna Cilleros-Portet ◽  
Sergi Marí ◽  
Rebeca Arauzo ◽  
...  
Keyword(s):  
Mendelian Randomization ◽  
Clear Cell ◽  
Association Studies ◽  
Epidemiological Data ◽  
Epidemiological Studies ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Genomic Analyses ◽  
Gynecological Disorder ◽  
Robust Evidence

Endometriosis is a common gynecological disorder that has been associated with endometrial, breast and epithelial ovarian cancers in epidemiological studies. Since complex diseases are a result of multiple environmental and genetic factors, we hypothesized that the biological mechanism underlying their comorbidity might be explained, at least in part, by shared genetics. To assess their potential genetic relationship, we performed a two-sample mendelian randomization (2SMR) analysis on results from public genome-wide association studies (GWAS). This analysis confirmed previously reported genetic pleiotropy between endometriosis and endometrial cancer. We present robust evidence supporting a causal genetic association between endometriosis and ovarian cancer, particularly with the clear cell and endometrioid subtypes. Our study also identified genetic variants that could explain those associations, opening the door to further functional experiments. Overall, this work demonstrates the value of genomic analyses to support epidemiological data, and to identify targets of relevance in multiple disorders.

scholarly journals Effects of thyroid hormone and depression on common components of central obesity

2019 ◽  
Vol 47 (7) ◽  
pp. 3040-3049 ◽  
Author(s):  
Fu-Man Du ◽  
Hong-Yu Kuang ◽  
Bin-Hong Duan ◽  
Da-Na Liu ◽  
Xin-Yang Yu
Keyword(s):  
Central Obesity ◽  
Low Density Lipoprotein ◽  
Fasting Blood Glucose ◽  
Density Lipoprotein ◽  
Epidemiological Studies ◽  
Thyroid Stimulating Hormone ◽  
Model Assessment ◽  
Free Triiodothyronine ◽  
Serum Tsh ◽  
Tsh Levels

Objective We investigated the prevalence of abnormal thyroid function and depression in centrally obese participants, and to analyze the relationship of thyroid hormones and depression with components of central obesity. Methods We randomly selected 858 centrally obese participants and 500 non-obese controls in this study. For all participants, we measured serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), body mass index (BMI), waist–hip ratio (WHR), fasting blood glucose and insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid concentrations, and blood pressure. Depression was assessed using the Center for Epidemiological Studies-Depression (CES-D) scale. Results Centrally obese participants had a higher prevalence of hypothyroidism and depression than non-obese controls. Serum FT4 levels negatively correlated with BMI and serum TSH levels and positively correlated with BMI, WHR, total triglycerides (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C). After excluding participants with hypothyroidism and hyperthyroidism, serum FT4 levels showed negative correlation and serum TSH levels showed positive correlation with BMI in the remaining centrally obese participants. CES-D scores positively correlated with BMI. Conclusion We found high prevalences of hypothyroidism and depression among centrally obese participants. FT4 and TSH are important in weight regulation. Depression positively correlated with obesity.

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 Impact of Cortisol on Reduction in Muscle Strength and Mass: A Mendelian Randomization Study

2021 ◽  
Author(s):  
Shunsuke Katsuhara ◽  
Maki Yokomoto-Umakoshi ◽  
Hironobu Umakoshi ◽  
Yayoi Matsuda ◽  
Norifusa Iwahashi ◽  
...  
Keyword(s):  
Muscle Strength ◽  
Grip Strength ◽  
Lean Mass ◽  
Bayesian Model Averaging ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Whole Body ◽  
Genome Wide Association Studies ◽  
Mass Estimate ◽  
The Impact

Abstract Purpose Prolonged exposure to pathological cortisol, as in Cushing’s syndrome causes various age-related disorders including sarcopenia. However, it is unclear whether mild cortisol excess, for example, accelerates sarcopenia due to aging or chronic stress. We performed a Mendelian randomization (MR) analysis to assess whether cortisol was causally associated with muscle strength and mass. Methods Three single nucleotide polymorphisms associated with plasma cortisol concentrations in the CORtisol NETwork consortium (n = 12,597) were used as instrumental variables. Summary statistics with traits of interest were obtained from relevant genome-wide association studies. For the primary analysis, we used the fixed-effects inverse-variance weighted analysis accounting for genetic correlations between variants. Results One standard deviation (SD) increase in cortisol was associated with SD reduction in grip strength (estimate, -0.032; 95% confidence interval [CI] -0.044 ~ -0.020; P = 3e-04), whole-body lean mass (estimate, -0.032; 95%CI, -0.046 ~ -0.017; P = 0.004), and appendicular lean mass (estimate, -0.031; 95%CI, -0.049 ~ -0.012; P = 0.001). The results were supported by the weighted-median analysis, with no evidence of pleiotropy in the MR-Egger analysis. The association of cortisol with grip strength and lean mass was observed in women but not in men. The association was attenuated after adjusting for fasting glucose in the multivariable MR analysis, which was the top mediator for the association in the MR-Bayesian model averaging analysis. Conclusion This MR study provides evidence for the association of cortisol with reduced muscle strength and mass, suggesting the impact of cortisol on the development of sarcopenia.

scholarly journals Causal Associations Between Educational Attainment and 14 Urological and Reproductive Health Outcomes: A Mendelian Randomization Study

2021 ◽  
Vol 9 ◽  
Author(s):  
Menghua Wang ◽  
Zhongyu Jian ◽  
Xiaoshuai Gao ◽  
Chi Yuan ◽  
Xi Jin ◽  
...  
Keyword(s):  
Reproductive Health ◽  
Educational Attainment ◽  
Health Outcomes ◽  
Lower Risk ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Causal Effects ◽  
Genome Wide Association Studies ◽  
Bonferroni Correction ◽  
The Impact

Background: The impact of educational attainment (EA) on multiple urological and reproductive health outcomes has been explored in observational studies. Here we used Mendelian randomization (MR) to investigate whether EA has causal effects on 14 urological and reproductive health outcomes.Methods: We obtained summary statistics for EA and 14 urological and reproductive health outcomes from genome-wide association studies (GWAS). MR analyses were applied to explore the potential causal association between EA and them. Inverse variance weighted was the primary analytical method.Results: Genetically predicted one standard deviation (SD) increase in EA was causally associated with a higher risk of prostate cancer [odds ratio (OR) 1.14, 95% confidence interval (CI) 1.05–1.25, P = 0.003] and a reduced risk of kidney stone (OR 0.73, 95% CI 0.62–0.87, P < 0.001) and cystitis (OR 0.76, 95% CI 0.67–0.86, P < 0.001) after Bonferroni correction. EA was also suggestively correlated with a lower risk of prostatitis (OR 0.76, 95% CI 0.59–0.98, P = 0.037) and incontinence (OR 0.64, 95% CI 0.47–0.87, P = 0.004). For the bioavailable testosterone levels and infertility, sex-specific associations were observed, with genetically determined increased EA being related to higher levels of testosterone in men (β 0.07, 95% CI 0.04–0.10, P < 0.001), lower levels of testosterone in women (β −0.13, 95% CI−0.16 to−0.11, P < 0.001), and a lower risk of infertility in women (OR 0.74, 95% CI 0.64–0.86, P < 0.001) but was not related to male infertility (OR 0.79, 95% CI 0.52–1.20, P = 0.269) after Bonferroni correction. For bladder cancer, kidney cancer, testicular cancer, benign prostatic hyperplasia, and erectile dysfunction, no causal effects were observed.Conclusions: EA plays a vital role in urological diseases, especially in non-oncological outcomes and reproductive health. These findings should be verified in further studies when GWAS data are sufficient.

scholarly journals 1402Thyroid stimulating hormone (TSH) is associated with general and abdominal obesity in girls during puberty

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Yingying Wang
Keyword(s):  
Logistic Regression ◽  
Abdominal Obesity ◽  
Regression Models ◽  
Population Based ◽  
Thyroid Stimulating Hormone ◽  
General Obesity ◽  
Logistic Regression Models ◽  
The Impact ◽  
Serum Tsh ◽  
Stimulating Hormone

Abstract Background Childhood is an important public health issue. Although both thyroid hormone and menarche are known to play a role in body metabolism and energy expenditure, no population-based study has been conducted to investigate the impact of TSH on adipogenesis among population-based girls around puberty. Methods A multi-stage cluster sampling method was used to select one junior middle school from each of 4 study areas: Minhang District in Shanghai, Haimen City in Jiangsu Province, Yuhuan City and Deqing County in Zhejiang Province. A total of 474 girls aged 11 to 14 years from 4 schools were enrolled. Information on demographic factors and puberty stage were collected, and anthropometric measurements and thyroid hormones were determined. Multivariate logistic regression models were used to assess the associations of Thyroid stimulating hormone (TSH) with the risk of obesity measured by body mess index (BMI) and waist circumference (WC). Results Of the 474 girls, the prevalences of BMI-based general obesity and WC-based abdominal obesity were 19.8% (94/474) and 21.7% (103/474), respectively. Compared with normal weight girls, the mean serum TSH concentration was significantly higher in BMI-based general overweight or obese girls (P = 0.037), but not in WC-based central overweight or obese girls (P = 0.173). In the multiple logistic regression models, for girls with highest tertile of serum TSH concentration relative to those in the lowest tertile, the odds ratios were 2.58 (95% CI 1.32 to 5.04) and 2.50 (95% CI 1.30 to 4.81) for overweight or obesity based on BMI and WC after adjustment for puberty stage and other covariates. Conclusions Serum TSH concentration was positively associated with both general and abdominal obesity in school-age girls and the association was independent of puberty. Key messages thyroid stimulating hormone; general obesity; central obesity; school-aged girls; puberty

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.

scholarly journals Association of Thyroid Function with Blood Pressure and Cardiovascular Disease: A Mendelian Randomization

2021 ◽  
Vol 11 (12) ◽  
pp. 1306
Author(s):  
Alice Giontella ◽  
Luca A. Lotta ◽  
John D. Overton ◽  
Aris Baras ◽  
Andrea Sartorio ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Thyroid Function ◽  
Lower Risk ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Sensitivity Analyses ◽  
Thyroid Peroxidase ◽  
Genome Wide Association Studies ◽  
Causal Association

Thyroid function has a widespread effect on the cardiometabolic system. However, the causal association between either subclinical hyper- or hypothyroidism and the thyroid hormones with blood pressure (BP) and cardiovascular diseases (CVD) is not clear. We aim to investigate this in a two-sample Mendelian randomization (MR) study. Single nucleotide polymorphisms (SNPs) associated with thyroid-stimulating hormone (TSH), free tetraiodothyronine (FT4), hyper- and hypothyroidism, and anti-thyroid peroxidase antibodies (TPOAb), from genome-wide association studies (GWAS), were selected as MR instrumental variables. SNPs–outcome (BP, CVD) associations were evaluated in a large-scale cohort, the Malmö Diet and Cancer Study (n = 29,298). Causal estimates were computed by inverse-variance weighted (IVW), weighted median, and MR-Egger approaches. Genetically increased levels of TSH were associated with decreased systolic BP and with a lower risk of atrial fibrillation. Hyperthyroidism and TPOAb were associated with a lower risk of atrial fibrillation. Our data support a causal association between genetically decreased levels of TSH and both atrial fibrillation and systolic BP. The lack of significance after Bonferroni correction and the sensitivity analyses suggesting pleiotropy, should prompt us to be cautious in their interpretation. Nevertheless, these findings offer mechanistic insight into the etiology of CVD. Further work into the genes involved in thyroid functions and their relation to cardiovascular outcomes may highlight pathways for targeted intervention.

MR-Corr2: a two-sample Mendelian randomization method that accounts for correlated horizontal pleiotropy using correlated instrumental variants

2021 ◽  
Author(s):  
Qing Cheng ◽  
Tingting Qiu ◽  
Xiaoran Chai ◽  
Baoluo Sun ◽  
Yingcun Xia ◽  
...  
Keyword(s):  
Complex Traits ◽  
Error Control ◽  
Type I Error ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Bivariate Normal Distribution ◽  
Supplementary Information ◽  
Type I ◽  
Genome Wide Association Studies ◽  
The Impact

Abstract Motivation Mendelian randomization (MR) is a valuable tool to examine the causal relationships between health risk factors and outcomes from observational studies. Along with the proliferation of genome-wide association studies, a variety of two-sample MR methods for summary data have been developed to account for horizontal pleiotropy (HP), primarily based on the assumption that the effects of variants on exposure (γ) and HP (α) are independent. In practice, this assumption is too strict and can be easily violated because of the correlated HP. Results To account for this correlated HP, we propose a Bayesian approach, MR-Corr2, that uses the orthogonal projection to reparameterize the bivariate normal distribution for γ and α, and a spike-slab prior to mitigate the impact of correlated HP. We have also developed an efficient algorithm with paralleled Gibbs sampling. To demonstrate the advantages of MR-Corr2 over existing methods, we conducted comprehensive simulation studies to compare for both type-I error control and point estimates in various scenarios. By applying MR-Corr2 to study the relationships between exposure–outcome pairs in complex traits, we did not identify the contradictory causal relationship between HDL-c and CAD. Moreover, the results provide a new perspective of the causal network among complex traits. Availability and implementation The developed R package and code to reproduce all the results are available at https://github.com/QingCheng0218/MR.Corr2. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Exploration of Lung Cancer-Related Genetic Factors via Mendelian Randomization Method Based on Genomic and Transcriptomic Summarized Data

2021 ◽  
Vol 9 ◽  
Author(s):  
Nitao Cheng ◽  
Xinran Cui ◽  
Chen Chen ◽  
Changsheng Li ◽  
Jingyu Huang
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Large Scale ◽  
Genetic Factors ◽  
Mendelian Randomization ◽  
Familial Aggregation ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Increased Risk ◽  
The Impact

Lung carcinoma is one of the most deadly malignant tumors in mankind. With the rising incidence of lung cancer, searching for the high effective cures become more and more imperative. There has been sufficient research evidence that living habits and situations such as smoking and air pollution are associated with an increased risk of lung cancer. Simultaneously, the influence of individual genetic susceptibility on lung carcinoma morbidity has been confirmed, and a growing body of evidence has been accumulated on the relationship between various risk factors and the risk of different pathological types of lung cancer. Additionally, the analyses from many large-scale cancer registries have shown a degree of familial aggregation of lung cancer. To explore lung cancer-related genetic factors, Genome-Wide Association Studies (GWAS) have been used to identify several lung cancer susceptibility sites and have been widely validated. However, the biological mechanism behind the impact of these site mutations on lung cancer remains unclear. Therefore, this study applied the Summary data-based Mendelian Randomization (SMR) model through the integration of two GWAS datasets and four expression Quantitative Trait Loci (eQTL) datasets to identify susceptibility genes. Using this strategy, we found ten of Single Nucleotide Polymorphisms (SNPs) sites that affect the occurrence and development of lung tumors by regulating the expression of seven genes. Further analysis of the signaling pathway about these genes not only provides important clues to explain the pathogenesis of lung cancer but also has critical significance for the diagnosis and treatment of lung cancer.

Sign in / Sign up

Export Citation Format

Share Document