Associations of GWAS-Supported Non-MHC Genes with Autoimmune Thyroiditis in Patients with Type 1 Diabetes

Liang, Jialin; Liang, Ganxiong; Z, Liu; Cai, Huan

doi:10.2147/dmso.s319630

Cited by 3 publications

(2 citation statements)

References 32 publications

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“…We would like to highlight that the variant rs6679677, which was significantly associated with T1DM, is situated between PHTF1 (Putative Homeodomain Transcription Factor 1) and RSBN1, which are implicated in systemic seropositive rheumatic diseases [37]. Although MR is a powerful statistical method used in epidemiology and genetics to assess causality between exposures, its effectiveness heavily depends on the critical assumption that the genetic variant serving as an IV remains unassociated with confounding factors.…”

Section: Discussionmentioning

confidence: 99%

Association between Type 1 Diabetes Mellitus and Parkinson’s Disease: A Mendelian Randomization Study

Mai,

Tan,

Sun

et al. 2024

JCM

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While much evidence suggests that type 2 diabetes mellitus increases the risk of Parkinson’s disease (PD), the relationship between type 1 diabetes mellitus (T1DM) and PD is unclear. To study their association, we performed a two-sample Mendelian randomization (MR) using the following statistical methods: inverse variance weighting (IVW), MR-Egger, weight median, and weighted mode. Independent datasets with no sample overlap were retrieved from the IEU GWAS platform. All the MR methods found a lower risk of PD in T1DM (IVW—OR 0.93, 95% CI 0.91–0.96, p = 3.12 × 10−5; MR-Egger—OR 0.93, 95% CI 0.88–0.98, p = 1.45 × 10−2; weighted median—OR 0.93, 95% CI 0.89–0.98, p = 2.76 × 10−3; and weighted mode—OR 0.94, 95% CI 0.9–0.98, p = 1.58 × 10−2). The findings were then replicated with another independent GWAS dataset on T1DM (IVW—OR 0.97, 95% CI 0.95–0.99, p = 3.10 × 10−3; MR-Egger—OR 0.96, 95% CI 0.93–0.99, p = 1.08 × 10−2; weighted median—OR 0.97, 95% CI 0.94–0.99, p = 1.88 × 10−2; weighted mode—OR 0.97, 95% CI 0.94–0.99, p = 1.43 × 10−2). Thus, our study provides evidence that T1DM may have a protective effect on PD risk, though further studies are needed to clarify the underlying mechanisms.

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Section: Discussionmentioning

confidence: 99%

Association between Type 1 Diabetes Mellitus and Parkinson’s Disease: A Mendelian Randomization Study

Mai,

Tan,

Sun

et al. 2024

JCM

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“…The SNPs were also utilized to investigate the association between thyroid disease and other diseases. QRFPR rs7679475 may exert an influence on the susceptibility of AT in patients with type 1 diabetes in Chinese Han population 14 . Hypothyroidism significantly increases the incidence of non-alcoholic fatty liver disease (NAFLD), while hyperthyroidism may act as a risk factor for NAFLD through MR analysis 15 and so forth.…”

Section: Introductionmentioning

confidence: 99%

Negative causal exploration of systemic sclerosis: a Mendelian randomization analysis

Han,

Wang

et al. 2024

Sci Rep

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Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune-related connective tissue disease with a complex and unknown pathophysiological mechanism with genes association. Several articles have reported a high prevalence of thyroid disease in SSc patients, while one study suggested a potential contribution of appendicitis to the development of SSc. To investigate this causal association, we conducted Mendelian randomization (MR) analysis using instrumental variables (IVs) to assess exposure and outcome. In the MR study involving two cohorts, all analyses were conducted using the TwoSampleMR package in R (version 4.3.0). Single nucleotide polymorphisms (SNPs) meeting a statistically significant threshold of 5E−08 were included in the analysis. Multiple complementary approaches including MR-IVW, MR-Egger, weighted median, simple mode, and weighted mode were employed to estimated the relationship between the exposure and outcome. Leave-one-out analysis and scatter plots were utilized for further investigation. Based on the locus-wide significance level, all of the MR analysis consequences manifested no causal association between the risk of appendicitis with SSc (IVW OR 0.319, 95% CI 0.063–14.055, P = 0.966). Negative causal effects of autoimmune thyroiditis (AT) on SSc (IVW OR 0.131, 95% CI 0.816–1.362, P = 0.686), Graves’ disease (GD) on SSc (IVW OR 0.097, 95% CI 0.837–1.222, P = 0.908), and hypothyroidism on SSc (IVW OR 1.136, 95% CI 0.977–1.321, P = 0.096) were derived. The reverse MR revealed no significant causal effect of SSc on thyroid disease. According to the sensitivity analysis, horizontal pleiotropy was unlikely to distort the causal estimates. The consequences indicated no significant association between AT, GD, and hypothyroidism with SSc. Similarly, there was no observed relationship with appendicitis.

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The 26RFa (QRFP)/GPR103 Neuropeptidergic System: A Key Regulator of Energy and Glucose Metabolism

Devère,

Takhlidjt,

Prévost

et al. 2024

Neuroendocrinology

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Background: Obesity and type 2 diabetes are strongly associated pathologies, currently considered as a worldwide epidemic problem. Understanding the mechanisms that drive the development of these diseases would enable to develop new therapeutic strategies for their prevention and treatment. Particularly, the role of the brain in the energy and glucose homeostasis has been studied for two decades. In specific, the hypothalamus contains well-identified neural networks regulating appetite and potentially also glucose homeostasis. A new concept has thus emerged, suggesting that obesity and diabetes could be due to a dysfunction of the same, still poorly understood, neural networks. Summary: The neuropeptide 26RFa (also termed QRFP) belongs to the family of RFamide regulatory peptides and has been identified as the endogenous ligand of the human G protein-coupled receptor GPR103 (QRFPR). The primary structure of 26RFa is strongly conserved during vertebrate evolution, suggesting its crucial roles in the control of vital functions. Indeed, the 26RFa/GPR103 peptidergic system is reported to be involved in the control of various neuroendocrine functions, notably the control of energy metabolism in which it plays an important role, both centrally and peripherally, since 26RFa regulates feeding behavior, thermogenesis and lipogenesis. Moreover, 26RFa is reported to control glucose homeostasis both peripherally, where it acts as an incretin, and centrally, where the 26RFa/GPR103 system relays insulin signaling in the brain to control glucose metabolism. Key Messages: This review gives a comprehensive overview of the role of the 26RFa/GPR103 system as a key player in the control of energy and glucose metabolism. In pathophysiological context, this neuropeptidergic system represents a prime therapeutic target whose mechanisms are highly relevant to decipher.

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Associations of GWAS-Supported Non-MHC Genes with Autoimmune Thyroiditis in Patients with Type 1 Diabetes

Cited by 3 publications

References 32 publications

Association between Type 1 Diabetes Mellitus and Parkinson’s Disease: A Mendelian Randomization Study

Association between Type 1 Diabetes Mellitus and Parkinson’s Disease: A Mendelian Randomization Study

Negative causal exploration of systemic sclerosis: a Mendelian randomization analysis

The 26RFa (QRFP)/GPR103 Neuropeptidergic System: A Key Regulator of Energy and Glucose Metabolism

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