Mendelian randomization analysis of Circulating adiponectin levels on prostate cancer

Abstract Background: Previous observational studies showed a conflict with the correlation between circulating adiponectin levels and prostate cancer. Methods: In this study, we employed Mendelian randomization analysis to identify the causal effects between them. 14 single nucleotide polymorphisms were screened from the largest-scale genome-wide association study meta-analysis of adiponectin in a multi-ethnic population. The SNP outcome effects were obtained from Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome and Japanese Encyclopedia of Genetic Associations by Riken. Inverse variance weighted model with random-effects was the main effect estimation in our study, alongside weighted median, MR-Egger, and weighted mode models.Results: The results showed no significant causal estimate but a potential protective effect of adiponectin on prostate cancer. In addition, two other research of adiponectin repeated the analysis to avoid the bias of human species showing the similar results. Conclusion: Our study did not provide significant evidence to support the causal effects of circulating adiponectin levels on prostate cancer, but most of our results showed a potential protective effect requiring larger-scale MR analysis to confirm.

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Genetically Determined Levels of Serum Metabolites and Risk of Neuroticism: A Mendelian Randomization Study

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyaa062 ◽

2020 ◽

Author(s):

Li Qian ◽

Yajuan Fan ◽

Fengjie Gao ◽

Binbin Zhao ◽

Bin Yan ◽

...

Keyword(s):

Uric Acid ◽

Lower Risk ◽

Genome Wide Association Study ◽

Mendelian Randomization ◽

Strong Predictor ◽

Causal Effects ◽

Sensitivity Analyses ◽

Nucleotide Polymorphisms ◽

Genetic Associations ◽

Inverse Variance

Abstract Background Neuroticism is a strong predictor for a variety of social and behavioral outcomes, but the etiology is still unknown. Our study aims to provide a comprehensive investigation of causal effects of serum metabolome phenotypes on risk of neuroticism using Mendelian randomization (MR) approaches. Methods Genetic associations with 486 metabolic traits were utilized as exposures, and data from a large genome-wide association study of neuroticism were selected as outcome. For MR analysis, we used the standard inverse-variance weighted (IVW) method for primary MR analysis and 3 additional MR methods (MR-Egger, weighted median, and MR pleiotropy residual sum and outlier) for sensitivity analyses. Results Our study identified 31 metabolites that might have causal effects on neuroticism. Of the 31 metabolites, uric acid and paraxanthine showed robustly significant association with neuroticism in all MR methods. Using single nucleotide polymorphisms as instrumental variables, a 1-SD increase in uric acid was associated with approximately 30% lower risk of neuroticism (OR: 0.77; 95% CI: 0.62–0.95; PIVW = 0.0145), whereas a 1-SD increase in paraxanthine was associated with a 7% higher risk of neuroticism (OR: 1.07; 95% CI: 1.01–1.12; PIVW = .0145). Discussion Our study suggested an increased level of uric acid was associated with lower risk of neuroticism, whereas paraxanthine showed the contrary effect. Our study provided novel insight by combining metabolomics with genomics to help understand the pathogenesis of neuroticism.

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A Two-Sample Mendelian Randomization Analysis Investigates Associations Between Gut Microbiota and Celiac Disease

Nutrients ◽

10.3390/nu12051420 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1420 ◽

Cited By ~ 4

Author(s):

Iraia García-Santisteban ◽

Ariadna Cilleros-Portet ◽

Elisabet Moyua-Ormazabal ◽

Alexander Kurilshikov ◽

Alexandra Zhernakova ◽

...

Keyword(s):

Celiac Disease ◽

Gut Microbiota ◽

Genome Wide Association Study ◽

Mendelian Randomization ◽

Outcome Data ◽

Nucleotide Polymorphisms ◽

Mendelian Randomization Analysis ◽

Immune Mediated ◽

And Function ◽

Randomization Analysis

Celiac disease (CeD) is a complex immune-mediated inflammatory condition triggered by the ingestion of gluten in genetically predisposed individuals. Literature suggests that alterations in gut microbiota composition and function precede the onset of CeD. Considering that microbiota is partly determined by host genetics, we speculated that the genetic makeup of CeD patients could elicit disease development through alterations in the intestinal microbiota. To evaluate potential causal relationships between gut microbiota and CeD, we performed a two-sample Mendelian randomization analysis (2SMR). Exposure data were obtained from the raw results of a previous genome-wide association study (GWAS) of gut microbiota and outcome data from summary statistics of CeD GWAS and Immunochip studies. We identified a number of putative associations between gut microbiota single nucleotide polymorphisms (SNPs) associated with CeD. Regarding bacterial composition, most of the associated SNPs were related to Firmicutes phylum, whose relative abundance has been previously reported to be altered in CeD patients. In terms of functional units, we linked a number of SNPs to several bacterial metabolic pathways that seemed to be related to CeD. Overall, this study represented the first 2SMR approach to elucidate the relationship between microbiome and CeD.

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GWAS-Based Multivariate Mendelian Randomization Analysis of Causal Effects of Lipoproteins on Coronary Artery Disease

SSRN Electronic Journal ◽

10.2139/ssrn.3294105 ◽

2018 ◽

Author(s):

Yuande Tan

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Mendelian Randomization ◽

Causal Effects ◽

Mendelian Randomization Analysis ◽

Artery Disease ◽

Randomization Analysis

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Testosterone in Female Depression: A Meta-Analysis and Mendelian Randomization Study

Biomolecules ◽

10.3390/biom11030409 ◽

2021 ◽

Vol 11 (3) ◽

pp. 409

Author(s):

Dhruba Tara Maharjan ◽

Ali Alamdar Shah Syed ◽

Guan Ning Lin ◽

Weihai Ying

Keyword(s):

Mendelian Randomization ◽

Meta Analysis ◽

Menopausal Status ◽

Serum Testosterone ◽

Serum Levels ◽

Testosterone Levels ◽

Mendelian Randomization Analysis ◽

The Difference ◽

Diagnostic Capabilities ◽

Randomization Analysis

Testosterone’s role in female depression is not well understood, with studies reporting conflicting results. Here, we use meta-analytical and Mendelian randomization techniques to determine whether serum testosterone levels differ between depressed and healthy women and whether such a relationship is casual. Our meta-analysis shows a significant association between absolute serum testosterone levels and female depression, which remains true for the premenopausal group while achieving borderline significance in the postmenopausal group. The results from our Mendelian randomization analysis failed to show any causal relationship between testosterone and depression. Our results show that women with depression do indeed display significantly different serum levels of testosterone. However, the directions of the effect of this relationship are conflicting and may be due to menopausal status. Since our Mendelian randomization analysis was insignificant, the difference in testosterone levels between healthy and depressed women is most likely a manifestation of the disease itself. Further studies could be carried out to leverage this newfound insight into better diagnostic capabilities culminating in early intervention in female depression.

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