Shared genetics and bidirectional causal relationships between type 2 diabetes and attention-deficit/hyperactivity disorder

General Psychiatry, Journal Year: 2023, Volume and Issue: 36(2), P. e100996 - e100996

Published: March 1, 2023

Type 2 diabetes (T2D) is a chronic metabolic disorder with high comorbidity mental disorders. The genetic links between attention-deficit/hyperactivity (ADHD) and T2D have yet to be elucidated.We aim assess shared genetics potential associations ADHD T2D.We performed correlation, two-sample Mendelian randomisation polygenic overlap analyses T2D. genome-wide association study (GWAS) summary results of (80 154 cases 853 816 controls), ADHD2019 (20 183 35 191 controls from the 2019 GWAS dataset) ADHD2022 (38 691 275 986 2022 were used for analyses. dataset was obtained DIAGRAM Consortium. datasets Psychiatric Genomics We compared signals reveal variation using larger dataset. Moreover, molecular pathways constructed based on large-scale literature data understand connection T2D.T2D has positive correlations (rg=0.33) (rg=0.31). Genetic liability associated an increased risk (odds ratio (OR): 1.30, p<0.001), while had suggestive causal effect (OR: p=0.086). higher 1.05, p=0.001) 1.03, p<0.001). analysis showed that most variants are ADHD2022. three overlapping loci. Molecular pathway suggests could promote each other through inflammatory pathways.Our demonstrates substantial bidirectional

Language: Английский

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Causal associations between major depressive disorder and COVID-19

General Psychiatry, Journal Year: 2023, Volume and Issue: 36(2), P. e101006 - e101006

Published: April 1, 2023

We aimed to evaluate whether major depressive disorder (MDD) could aggravate the outcomes of coronavirus disease 2019 (COVID-19) or genetic liability COVID-19 trigger MDD.We assess bidirectional causal associations between MDD and COVID-19.We performed correlation Mendelian randomisation (MR) analyses potential three outcomes. Literature-based network analysis was conducted construct molecular pathways connecting found that has positive correlations with (rg: 0.10-0.15). Our MR indicated is associated increased risks infection (odds ratio (OR)=1.05, 95% confidence interval (CI): 1.00 1.10, p=0.039). However, did not confer any effects on MDD. Pathway identified a panel immunity-related genes may mediate links COVID-19.Our study suggests increase susceptibility COVID-19. findings emphasise need social support improve mental health intervention networks for people mood disorders during pandemic.

Language: Английский

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Causal associations and shared genetics between hypertension and COVID‐19

Journal of Medical Virology, Journal Year: 2023, Volume and Issue: 95(4)

Published: March 23, 2023

To evaluate the genetic relationship between hypertension and COVID-19 explore molecular pathways linking to COVID-19. We performed correlation Mendelian randomization (MR) analyses assess potential associations hospitalized compared genome-wide association signals reveal shared variation Moreover, hypertension-driven were constructed based on large-scale literature data understand influence of at level. Hypertension has a positive with (rg = 0.19). The MR indicate that liability confers causal effect (odds ratio [OR]: 1.05, confidence interval [CI]: 1.00-1.09, p 0.030). have three overlapping loci share eight protein-coding risk genes, including ABO, CSF2, FUT2, IZUMO1, MAMSTR, NPNT, RASIP1, WNT3. Molecular pathway analysis suggests may promote development through induction inflammatory pathways. Our study genetically determined increase for severe connecting underline links

Language: Английский

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COVID-19 vaccination and the risk of autoimmune diseases: a Mendelian randomization study

Frontiers in Public Health, Journal Year: 2024, Volume and Issue: 12

Published: March 14, 2024

Background In recent times, reports have emerged suggesting that a variety of autoimmune disorders may arise after the coronavirus disease 2019 (COVID-19) vaccination. However, causality and underlying mechanisms remain unclear. Methods We collected summary statistics COVID-19 vaccination 31 diseases from genome-wide association studies (GWAS) as exposure outcome, respectively. Random-effects inverse variance weighting (IVW), MR Egger, weighted median, simple mode, mode were used analytical methods through Mendelian randomization (MR), heterogeneity sensitivity analysis performed. Results selected 72 instrumental variables for ( p &lt; 5 × 10 −6 ; r2 0.001, genetic distance = 10,000 kb), analyses showed was causally associated with an increased risk multiple sclerosis (MS) (IVW, OR: 1.53, 95% CI: 1.065–2.197, 0.026) ulcerative colitis (UC) 1.00, 1.000–1.003, 0.039). If refined −8 associations became negative. No found remaining outcomes. These results robust to analyses. Conclusion Our study provided potential evidence impact on MS UC occurrence, but it lacks sufficient robustness, which could provide new idea public health policy.

Language: Английский

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Shared genetics and causal associations between COVID‐19 and multiple sclerosis

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 95(1)

Published: Dec. 26, 2022

Neuroinflammation caused by COVID-19 negatively impacts brain metabolism and function, while pre-existing pathology may contribute to individuals' vulnerability the adverse consequences of COVID-19. We used summary statistics from genome-wide association studies (GWAS) perform Mendelian randomization (MR) analyses, thus assessing potential associations between multiple sclerosis (MS) two outcomes (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection hospitalization). Genome-wide risk genes were compared GWAS datasets on hospitalized MS. Literature-based analysis was conducted construct molecular pathways connecting MS found that genetic liability confers a causal effect (odd ratio [OR]: 1.09, 95% confidence interval: 1.03-1.16) but not SARS-CoV-2 (1.03, 1.00-1.05). Genetic (1.15, 1.02-1.30). Hospitalized share five within loci, including TNFAIP8, HSD17B4, CDC37, PDE4A, KEAP1. Pathway identified panel immunity-related mediate links Our study suggests associated with 9% increased for hospitalization, 15% Immunity-related underlie link

Language: Английский

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Causal associations and genetic overlap between COVID-19 and intelligence

QJM, Journal Year: 2023, Volume and Issue: 116(9), P. 766 - 773

Published: June 7, 2023

COVID-19 might cause neuroinflammation in the brain, which could decrease neurocognitive function. We aimed to evaluate causal associations and genetic overlap between intelligence.We performed Mendelian randomization (MR) analyses assess potential three outcomes intelligence (N = 269 867). The COVID phenotypes included severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection 501 486), hospitalized 1 965 329) critical 743 167). Genome-wide risk genes were compared genome-wide association study (GWAS) datasets on intelligence. In addition, functional pathways constructed explore molecular connections intelligence.The MR indicated that liabilities SARS-CoV-2 (odds ratio [OR]: 0.965, 95% confidence interval [CI]: 0.939-0.993) (OR: 0.989, CI: 0.979-0.999) confer effects There was suggestive evidence supporting effect of 0.988, 0.972-1.003). Hospitalized share 10 within genomic loci, including MAPT WNT3. Enrichment analysis showed these are functionally connected distinct subnetworks 30 linked cognitive decline. pathway revealed COVID-19-driven pathological changes brain multiple peripheral systems may lead impairment.Our suggests exert a detrimental tau protein Wnt signaling mediate influence

Language: Английский

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The causal role of gut microbiota in susceptibility and severity of COVID‐19: A bidirectional Mendelian randomization study

Journal of Medical Virology, Journal Year: 2023, Volume and Issue: 95(7)

Published: July 1, 2023

Growing evidence has shown that altered gut microbiota is associated with the pathogenesis of COVID-19, but their causal effects are still unclear. We conducted a bidirectional Mendelian randomization (MR) study to assess on COVID-19 susceptibility or severity, and vice versa. The microbiome genome-wide association studies (GWAS) data 18 340 individuals GWAS statistics from host genetics initiative (38 984 European patients 1 644 784 controls) were used as exposure outcomes. inverse variance weighted (IVW) was primary MR analysis. Sensitivity analyses performed validate robustness, pleiotropy, heterogeneity results. In forward MR, we identified several microbial genera (p < 0.05 FDR 0.1): Alloprevotella (odds ratio [OR]: 1.088, 95% confidence interval [CI]: 1.021-1.160), Coprococcus (OR: 1.159, CI: 1.030-1.304), Parasutterella 0.902, 0.836-0.973), Ruminococcaceae UCG014 0.878, 0.777-0.992). Reverse had depletion families Lactobacillaceae (Beta [SE]: -0.220 [0.101]) Lachnospiraceae (-0.129 [0.062]), Flavonifractor (-0.180 [0.081]) Lachnoclostridium [-0.181 [0.063]). Our findings supported effect infection might further causally induce dysbiosis.

Language: Английский

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Causal Associations between Posttraumatic Stress Disorder and COVID-19

Journal of Integrative Neuroscience, Journal Year: 2024, Volume and Issue: 23(4), P. 68 - 68

Published: April 1, 2024

Objective: We aimed to evaluate bidirectional genetic relationships between posttraumatic stress disorder (PTSD) and COVID-19. Methods: investigated potential causal associations PTSD two COVID-19 conditions (COVID-19 hospitalization SARS-CoV-2 infection) via Mendelian randomization (MR) analyses. Three genome-wide association study (GWAS) summary datasets were used in the study, including (N = 174,659), infection 2,597,856), 2,095,324). performed a literature-based analysis uncover molecular pathways connecting Results: found that exerts effect on (odds ratio (OR): 1.10, 95% confidence interval (CI): 1.00–1.21, p 0.048) hospitalized (OR: 1.34, CI: 1.07–1.67, 0.001). However, both not associated with risk of PTSD. Pathway revealed several immunity-related genes may link Conclusions: Our suggests was increased risks for susceptibility severity. Early diagnosis effective treatment individuals infected coronavirus improve management outcomes

Language: Английский

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A systematic review of Mendelian randomization studies on multiple sclerosis

European Journal of Neuroscience, Journal Year: 2023, Volume and Issue: 58(4), P. 3172 - 3194

Published: July 18, 2023

Abstract Mendelian randomization (MR) is a powerful approach for assessing the causal effect of putative risk factors on an outcome, using genetic variants as instrumental variables. The methodology and application developed in framework MR have been dramatically improved, taking advantage many public genome‐wide association study (GWAS) data. availability summary‐level data allowed to perform numerous studies especially complex diseases, pinpointing modifiable exposures causally related increased or decreased disease risk. Multiple sclerosis (MS) multifactorial whose aetiology involves both non‐genetic their interplay. Previous observational revealed associations between candidate MS risk; although being prone confounding, reverse causation, these were unable draw conclusions. analysis addresses limitations allows establish reliable accurate Here, we systematically reviewed evaluating effect, through MR, Among 107 papers found, only 42 eligible final evaluation qualitative synthesis. We found that, above all, low vitamin D levels high adult body mass index (BMI) appear be uncontested

Language: Английский

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Exploring the causal effects of depression and antidepressants on COVID-19

Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: 359, P. 350 - 355

Published: May 25, 2024

Language: Английский

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