Genetic association between circulating selenium level and the risk of schizophrenia in the European population: A two-sample Mendelian randomization study

Deng, Minggang; Cui, Han-Tao; Nie, Jia-Qi; Liang, Yuehui; Chai, Chen

doi:10.3389/fnut.2022.969887

Cited by 13 publications

(9 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The LDSC method indicated that genetic variants related to depression [ r g = 0.157, se = 0.023, p = 3.52×10 -12 ] and SCZ ( r g = 0.042, se = 0.020, p = 0.042) were positively correlated with AAA, while BIP was not ( r g = 0.013, se = 0.023, p = 0.591). Additionally, the GNOVA method estimates further supported these findings, indicating a positive association of AAA with depression ( r g = 0.152, se = 0.019, p = 8.41× -16 ) and SCZ ( r g = 0.053, se = 0.017, p = 0.002). Conversely, BIP did not demonstrate a significant association with AAA ( r g = 0.021, se = 0.019, p = 0.272).…”

Section: Resultsmentioning

confidence: 59%

“…These findings enhance the statistical power and offer the opportunity to explore their genetic associations. In addition, Mendelian Randomization (MR), which uses genetic variants (single nucleotide polymorphisms, SNPs) as instruments, is a powerful method for obtaining robust causal inference 15 and has been widely utilized in recent epidemiological research 16–18 . As a result, this study aims to investigate the genetic correlation between AAA and mental disorders and to utilize the MR design to evaluate their causality.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Relationship between mental disorders and abdominal aortic aneurysm: insights from genetic perspectives

Deng,

Chai,

Wang

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Objective:To explore the correlation or potential causation between mental disorders [depression, schizophrenia (SCZ), bipolar disorder (BIP)], and abdominal aortic aneurysm (AAA). <br />Methods:Summary-level genetic data sets were obtained from the large-scale genome-wide association studies. We first investigated the genetic correlation between AAA and mental disorders from the perspectives of global/local genetic correlation and shared genomic loci. Following that, bidirectional univariable Mendelian Randomization (UMR) was conducted to assess their causal relationship, with multivariable MR (MVMR) to control the effect from confounders. Finally, the mediation analyses were performed to evaluate whether the causality was mediated by the known risk factors, e.g., smoking and hypertension. <br />Results:Global genetic correlation analyses presented that depression and SCZ were correlated with AAA, while BIP was not. Besides, AAA was found to be locally correlated with depression, SCZ, and BIP in 4, 7, 10 genomic regions, respectively. Additionally, a total 26, 141, and 10 shared genomic loci were respectively found between AAA and depression, SCZ, and BIP. The UMR analyses indicated genetically predicted depression (OR: 1.270, 95% CI: 1.071-1.504, p = 0.006) and SCZ (OR: 1.047, 95% CI: 1.010-1.084, p = 0.011) were associated with elevated risk of AAA, while no causal effects of BIP on AAA, and AAA on three mental disorders were found. These associations were consistently robust in MVMR analyses. The mediation analyses indicated the causal effect of depression on AAA was mediated by smoking, hypertension, and hyperlipidemia, as well as coronary atherosclerosis, and smoking mediated the effect of SCZ on AAA. <br />Conclusion:Genetically predicted depression and SCZ were associated with elevated risk of AAA, and the known risk factors of AAA playing the mediation roles.

show abstract

Section: Resultsmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Relationship between mental disorders and abdominal aortic aneurysm: insights from genetic perspectives

Deng,

Chai,

Wang

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Genetic epidemiology established another approach to address these conundrums. Mendelian randomization (MR) is a genetic instrumental variable analysis approach based on genetic variants associated with the exposures of interest, which serve as un‐confounded proxies, which has been applied in genetic epidemiology to circumvent issues of confounding and reverse causation (Skrivankova et al., 2021; Deng et al., 2023). Since the genotype subgroups were randomly inherited from parents to offspring, independent of concerning confounding factors that influenced the exposure of interest (known as SNPs) and unaffected by reverse causation, if instrumental variable assumptions are all met.…”

Section: Introductionmentioning

confidence: 99%

Maternal history of Alzheimer's disease predisposes to altered serum cholesterol levels in adult offspring

Liang,

Deng,

Jian

et al. 2024

Journal of Neurochemistry

View full text Add to dashboard Cite

Controversial findings regarding the association between serum cholesterol levels and Alzheimer's disease (AD) have been identified through observational studies. The genetic basis shared by both factors and the causality between them remain largely unknown. The objective of this study is to examine the causal impact of maternal history of AD on changes in serum cholesterol levels in adult offspring. By retrieving genetic variants from summary statistics of large‐scale genome‐wide association study of maternal history of AD (European‐based: Ncase = 27 696, Ncontrol = 260 980). The causal association between genetically predicted maternal history of AD and changes in serum cholesterol levels in adult offspring was examined using the two‐sample Mendelian randomization (MR) method. Causal impact estimates were calculated using single‐nucleotide polymorphisms in both univariable MR (UMR) and multivariable MR (MVMR) analyses. Additionally, other approaches, such as Cochran's Q test and leave‐one‐out variant analysis, were employed to correct for potential biases. The results of UMR presented that genetically predicted maternal history of AD was positively associated with hypercholesterolemia (OR = 1.014; 95% CI: 1.009–1.018; p < 0.001), total cholesterol (OR = 1.29; 95% CI: 1.134–1.466; p < 0.001) and low‐density lipoprotein (OR = 1.525; 95% CI: 1.272–1.828; p < 0.001) among adult offspring. Genetic predisposition for maternal history of AD to be negatively associated with high‐density lipoprotein (OR = 0.889; 95% CI: 0.861–0.917; p < 0.001). The MVMR analysis remained robust and significant after adjusting for diabetes and obesity in offspring. Sufficient evidence was provided in this study to support the putative causal impact of maternal history of AD on the change of serum cholesterol profile in adult offspring. In clinical practice, priority should be given to the detection and monitoring of cholesterol levels in individuals with a maternal history of AD, particularly in the early stages.

show abstract

“…As a statistical approach reminiscent of randomized controlled trials, Mendelian randomization (MR) utilizes genetic variation to determine whether the association observed between a risk factor and outcomes is indicative of the existence of a causal relationship [ 15 , 16 ]. Although confounding bias and reverse causality are common limitations in observational studies, they are less likely to appear in MR analyses since genotype formation precedes disease onset [ 17 ]. Several MR analyses have confirmed the causal relationship between IPF and exposures such as body mass index (BMI) [ 18 ], circulating proteins [ 19 ], comorbidities (including gastroesophageal reflux disease (GERD) [ 20 ], hypothyroidism [ 21 ], venous thromboembolism [ 22 ], chronic obstructive pulmonary disease [ 22 ], and diabetes [ 22 ]).…”

Section: Introductionmentioning

confidence: 99%

The causal relationship between genetically predicted blood metabolites and idiopathic pulmonary fibrosis: A bidirectional two-sample Mendelian randomization study

Pan,

Bai,

Zhu

et al. 2024

PLoS ONE

View full text Add to dashboard Cite

Background Numerous metabolomic studies have confirmed the pivotal role of metabolic abnormalities in the development of idiopathic pulmonary fibrosis (IPF). Nevertheless, there is a lack of evidence on the causal relationship between circulating metabolites and the risk of IPF. Methods The potential causality between 486 blood metabolites and IPF was determined through a bidirectional two-sample Mendelian randomization (TSMR) analysis. A genome-wide association study (GWAS) involving 7,824 participants was performed to analyze metabolite data, and a GWAS meta-analysis involving 6,257 IPF cases and 947,616 control European subjects was conducted to analyze IPF data. The TSMR analysis was performed primarily with the inverse variance weighted model, supplemented by weighted mode, MR-Egger regression, and weighted median estimators. A battery of sensitivity analyses was performed, including horizontal pleiotropy assessment, heterogeneity test, Steiger test, and leave-one-out analysis. Furthermore, replication analysis and meta-analysis were conducted with another GWAS dataset of IPF containing 4,125 IPF cases and 20,464 control subjects. Mediation analyses were used to identify the mediating role of confounders in the effect of metabolites on IPF. Results There were four metabolites associated with the elevated risk of IPF, namely glucose (odds ratio [OR] = 2.49, 95% confidence interval [95%CI] = 1.13–5.49, P = 0.024), urea (OR = 6.24, 95% CI = 1.77–22.02, P = 0.004), guanosine (OR = 1.57, 95%CI = 1.07–2.30, P = 0.021), and ADpSGEGDFXAEGGGVR (OR = 1.70, 95%CI = 1.00–2.88, P = 0.0496). Of note, the effect of guanosine on IPF was found to be mediated by gastroesophageal reflux disease. Reverse Mendelian randomization analysis displayed that IPF might slightly elevate guanosine levels in the blood. Conclusion Conclusively, hyperglycemia may confer a promoting effect on IPF, highlighting that attention should be paid to the relationship between diabetes and IPF, not solely to the diagnosis of diabetes. Additionally, urea, guanosine, and ADpSGEGDFXAEGGGVR also facilitate the development of IPF. This study may provide a reference for analyzing the potential mechanism of IPF and carry implications for the prevention and treatment of IPF.

show abstract

Genetic association between circulating selenium level and the risk of schizophrenia in the European population: A two-sample Mendelian randomization study

Cited by 13 publications

References 38 publications

Relationship between mental disorders and abdominal aortic aneurysm: insights from genetic perspectives

Relationship between mental disorders and abdominal aortic aneurysm: insights from genetic perspectives

Maternal history of Alzheimer's disease predisposes to altered serum cholesterol levels in adult offspring

The causal relationship between genetically predicted blood metabolites and idiopathic pulmonary fibrosis: A bidirectional two-sample Mendelian randomization study

Contact Info

Product

Resources

About