Causal Association between Rheumatoid Arthritis with the Increased Risk of Type 2 Diabetes: A Mendelian 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.

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Network Mendelian randomization study: exploring the causal pathway from insomnia to type 2 diabetes

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2021-002510 ◽

2022 ◽

Vol 10 (1) ◽

pp. e002510

Author(s):

Wen Xiuyun ◽

Lin Jiating ◽

Xie Minjun ◽

Li Weidong ◽

Wu Qian ◽

...

Keyword(s):

Type 2 Diabetes ◽

Body Fat ◽

Mendelian Randomization ◽

Body Fat Percentage ◽

Causal Association ◽

Fat Percentage ◽

Waist To Hip Ratio ◽

Increased Risk ◽

Causal Pathway

IntroductionInsomnia is a novel pathogen for type 2 diabetes mellitus (T2DM). However, mechanisms linking insomnia and T2DM are poorly understood. In this study, we apply a network Mendelian randomization (MR) framework to determine the causal association between insomnia and T2DM and identify the potential mediators, including overweight (body mass index (BMI), waist-to-hip ratio, and body fat percentage) and glycometabolism (HbA1c, fasting blood glucose, and fasting blood insulin).Research design and methodsWe use the MR framework to detect effect estimates of the insomnia–T2DM, insomnia–mediator, and mediator–T2DM associations. A mediator between insomnia and T2DM is established if MR studies in all 3 steps prove causal associations.ResultsIn the Inverse variance weighted method, the results show that insomnia will increase the T2DM risk (OR 1.142; 95% CI 1.072 to 1.216; p=0.000), without heterogeneity nor horizontal pleiotropy, strongly suggesting that genetically predicted insomnia has a causal association with T2DM. Besides, our MR analysis provides strong evidence that insomnia is causally associated with BMI and body fat percentage. There is also suggestive evidence of an association between insomnia and the waist-to-hip ratio. At the same time, our results indicate that insomnia is not causally associated with glycometabolism. Higher BMI, waist-to-hip ratio, and body fat percentage levels are strongly associated with increased risk of T2DM.ConclusionsGenetically predicted insomnia has a causal association with T2DM. Being overweight (especially BMI and body fat percentage) mediates the causal pathway from insomnia to T2DM.

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