rs34331204 regulates <i>TSPAN13</i> expression and contributes to Alzheimer’s disease with sex differences

Hu, Yang; Zhang, Haihua; Liu, Bian; Gao, Shan; Wang, Tao; Han, Zhifa; Ji, Xunming; Liu, Guiyou

doi:10.1093/brain/awaa302

Cited by 51 publications

(28 citation statements)

References 26 publications

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“…Therefore, it was difficult for observational studies to determine the causal direction of this association. The genetic determinants of cardiovascular diseases and neurodegenerative diseases have been increasingly wellcharacterized (Greuel et al, 2020;Hu et al, 2020Hu et al, , 2021a. In our MR study, we suggested an association between television watching with worse CP, which was consistent with previous studies (Falck et al, 2017;Stubbs et al, 2017).…”

Section: Discussionsupporting

confidence: 92%

Genetic Liability to Sedentary Behavior in Relation to Stroke, Its Subtypes and Neurodegenerative Diseases: A Mendelian Randomization Study

Yang

Chen

et al. 2021

Front. Aging Neurosci.

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Objective: To investigate the causal association of domain-specific sedentary behaviors with cerebrovascular diseases and neurodegenerative diseases, and the potential mediators among these associations.Methods: Genetic instruments were identified for television watching, computer use and driving behavior from a genome-wide association study including 408,815 subjects. Mendelian randomization (MR) analysis was used to estimate the causal effect of sedentary behaviors on the cerebrovascular diseases and neurodegenerative diseases. Multivariable MR analysis was applied to adjust potential confounding factors, and mediation analysis was conducted to explore potential mediators.Results: Genetically predisposition to 1.5 h/day increase in leisure time watching television was associated with increased risk of all-cause stroke [odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.15–1.52, p-value for MR-Egger method (PEgger) = 0.11, I2 = 37%, Cochrane’s Q = 212, p-value for Cochran Q test (PQ) < 0.001], and ischemic stroke (OR = 1.28, 95%CI = 1.10–1.49, PEgger = 0.04, I2 = 35%, Cochrane’s Q = 206, PQ = 0.002). Interestingly, television watching may decrease the risk of Parkinson’s disease (OR = 0.65, 95%CI = 0.50–0.84, PEgger = 0.47, I2 = 19%, Cochrane’s Q = 157, PQ = 0.04). Television watching was a detrimental factor of cognitive performance (estimate = −0.46, 95%CI = −0.55 – −0.37, PEgger = 0.001, I2 = 85%, Cochrane’s Q = 862, PQ < 0.001). Sensitivity analyses using leave out method and MR-PRESSO method suggested weak evidence of pleiotropy.Conclusion: We provided genetic evidence for the causal association of television watching with increased risk of all-cause stroke and ischemic stroke, decreased risk of Parkinson’s disease, and worse cognitive performance. The results should be interpreted with caution considering the pleiotropy.

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Section: Discussionsupporting

confidence: 92%

Genetic Liability to Sedentary Behavior in Relation to Stroke, Its Subtypes and Neurodegenerative Diseases: A Mendelian Randomization Study

Yang

Chen

et al. 2021

Front. Aging Neurosci.

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“…In previous studies, the association between hypothyroidism and NAFLD has been researched from various perspectives, both clinically ( Chung et al, 2012 ; Pagadala et al, 2012 ; Lee et al, 2015 ; Ludwig et al, 2015 ; Mantovani et al, 2018 ; Hu et al, 2019 , 2020 , 2021 ) and biologically ( Ferrandino et al, 2017 ; Gionfra et al, 2019 ; Lonardo et al, 2019 ). The causality, however, is still unexplored ( Efstathiadou et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Exploring the Causality Between Hypothyroidism and Non-alcoholic Fatty Liver: A Mendelian Randomization Study

Qiu

Cao

Guo

et al. 2021

Front. Cell Dev. Biol.

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The etiology of non-alcoholic fatty liver disease (NAFLD) involves complex interaction of genetic and environmental factors. A large number of observational studies have shown that hypothyroidism contributes to a high risk of NAFLD. However, the exact causality is still unknown. Due to the progress of genome-wide association study (GWAS) and the discovery of Mendelian randomization (MR), it is possible to explore the causality between the two diseases. In this study, in order to research into the influence of intermediate phenotypes on outcome, nine independent genetic variants of hypothyroidism obtained from the GWAS were used as instrumental variables (IVs) to perform MR analysis on NAFLD. Since there was no heterogeneity between IVs (P = 0.70), a fixed-effects model was used. The correlation between hypothyroidism and NAFLD was evaluated by using inverse-variance weighted (IVW) method and weighted median method. Then the sensitivity test was analyzed. The results showed that there was a high OR (1.7578; 95%CI 1.1897–2.5970; P = 0.0046) and a low intercept (−0.095; P = 0.431). None of the genetic variants drove the overall result (P < 0.01). Simply, we proved for the first time that the risk of NAFLD increases significantly on patients with hypothyroidism. Furthermore, we explained possible causes of NAFLD caused by hypothyroidism.

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“…M1-like macrophages were grouped into pattern 1 and SPP1 (secreted phosphoprotein 1), NPR2 (Natriuretic Peptide Receptor 2) and CCL (Chemokine ligands) may be possible significant pathways. Moreover, GSVA software was utilized to identify differences in hallmark gene sets of Molecular Signatures Database (MSigDB) across different cell types [ 48 , [52] , [53] , [54] , [55] ]. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Single-cell RNA analysis reveals the potential risk of organ-specific cell types vulnerable to SARS-CoV-2 infections

Zhang

Cui

Cao

et al. 2022

Computers in Biology and Medicine

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rs34331204 regulates TSPAN13 expression and contributes to Alzheimer’s disease with sex differences

Cited by 51 publications

References 26 publications

Genetic Liability to Sedentary Behavior in Relation to Stroke, Its Subtypes and Neurodegenerative Diseases: A Mendelian Randomization Study

Genetic Liability to Sedentary Behavior in Relation to Stroke, Its Subtypes and Neurodegenerative Diseases: A Mendelian Randomization Study

Exploring the Causality Between Hypothyroidism and Non-alcoholic Fatty Liver: A Mendelian Randomization Study

Single-cell RNA analysis reveals the potential risk of organ-specific cell types vulnerable to SARS-CoV-2 infections

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