Mendelian randomization: causal inference leveraging genetic data

Psychological Medicine, Journal Year: 2024, Volume and Issue: 54(8), P. 1461 - 1474

Published: April 19, 2024

Mendelian randomization (MR) leverages genetic information to examine the causal relationship between phenotypes allowing for presence of unmeasured confounders. MR has been widely applied unresolved questions in epidemiology, making use summary statistics from genome-wide association studies on an increasing number human traits. However, understanding essential concepts is necessary appropriate application and interpretation MR. This review aims provide a non-technical overview demonstrate its relevance psychiatric research. We begin with origins reasons recent expansion, followed by statistical methodology. then describe limitations MR, how these are being addressed methodological advances. showcase practical psychiatry through three illustrative examples - connection cannabis psychosis, link intelligence schizophrenia, search modifiable risk factors depression. The concludes discussion prospects focusing integration multi-omics data extension delineating complex networks.

Language: Английский

---

Structural and functional MRI correlates of inflammation in bipolar disorder: A systematic review

Journal of Affective Disorders, Journal Year: 2023, Volume and Issue: 325, P. 83 - 92

Published: Jan. 5, 2023

Bipolar disorder (BD) is a common affective characterized by recurrent oscillations between mood states and associated with inflammatory diseases chronic inflammation. However, data on MRI abnormalities in BD their relationship inflammation are heterogeneous no review has recapitulated them. In this pre-registered (PROSPERO: CRD42022308461) systematic we searched Web of Science Core Collection PubMed for articles correlating functional or structural measures immune-related markers BD. We included 23 studies (6 functional, 16 findings, 1 both, including 1'233 patients). Overall, the quality was fair, low risk bias. Heterogeneity methods results small sample sizes limit generalizability conclusions. A qualitative synthesis suggests that links immune traits alterations point toward brain areas involved somatomotor processing, trend negative correlation peripheral regions volume. discuss how disentangling complex system may unveil mechanisms underlying symptoms pathophysiology, potentially quickly translatable diagnostic, prognostic, therapeutic implications.

Language: Английский

---

Inflammation and emotion regulation: a narrative review of evidence and mechanisms in emotion dysregulation disorders

Neuronal Signaling, Journal Year: 2023, Volume and Issue: 7(4)

Published: Oct. 27, 2023

Abstract Emotion dysregulation (ED) describes a difficulty with the modulation of which emotions are felt, as well when and how these experienced or expressed. It is focal overarching symptom in many severe prevalent neuropsychiatric diseases, including bipolar disorders (BD), attention deficit/hyperactivity disorder (ADHD), borderline personality (BPD). In all disorders, ED can manifest through symptoms depression, anxiety, affective lability. Considering symptomatic similarities between BD, ADHD, BPD, transdiagnostic approach promising lens investigation. Mounting evidence supports role peripheral inflammatory markers stress multifactorial aetiology physiopathology BPD. Of note, neural circuits that regulate appear particularly vulnerable to insults inflammation, impact neuroimmune milieu central nervous system. Thus far, few studies have examined link inflammation To our knowledge, no specific work has provided critical comparison results from disorders. fill this gap literature, we review known associations mechanisms linking general, clinically, BD. Our narrative begins an examination routes followed by discussion disorder-specific accounting for methodological limitations relevant confounding factors. Finally, critically discuss both correspondences discrepancies comment on potential vulnerability therapeutic interventions.

Language: Английский

---

Schizophrenia genomics: genetic complexity and functional insights

Nature reviews. Neuroscience, Journal Year: 2024, Volume and Issue: 25(9), P. 611 - 624

Published: July 19, 2024

Language: Английский

---

Shared and unique characteristics of metabolic syndrome in psychotic disorders: a review

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: March 4, 2024

Introduction People with psychosis spectrum disorders (PSD) face an elevated risk of metabolic syndrome (MetS), which may reduce their life expectancy by nearly 20%. Pinpointing the shared and specific characteristics clinical implications MetS in PSD is crucial for designing interventions to this risk, but up-to-date review on across lacking. Methods This narrative fills gap examining literature both distinct transdiagnostically, i.e., traditional categorical diagnoses, a focus psychiatric cardio-metabolic management. Results We discuss common PSD, as well factors contributing development patients, including unhealthy lifestyle factors, genetic predisposition, pro-inflammatory state, drugs consumption, antipsychotic medication, psychotic symptoms. highlight importance early identification management existing gaps literature, instance screening younger patients. compare hypotheses-generating associations different concluding reviewing recommendations challenges screening, monitoring, managing PSD. Conclusion Early are mitigate long-term toll Interventions should healthy appropriate pharmacological behavioral interventions. Further translational research needed develop targeted personalized treatment approaches vulnerable population, aiming at improving physical health overall well-being.

Language: Английский

---

Assessing the Role of Cortisol in Anxiety, Major Depression, and Neuroticism: A Mendelian Randomization Study Using SERPINA6/SERPINA1 Variants

Biological Psychiatry Global Open Science, Journal Year: 2024, Volume and Issue: 4(3), P. 100294 - 100294

Published: Feb. 18, 2024

Previous evidence informed by the toxic stress model suggests that higher cortisol causes anxiety and major depression, but clinical success is lacking. To clarify role of cortisol, we used Mendelian randomization to estimate its associations with anxiety, neuroticism, leveraging largest available genome-wide association studies including from Psychiatric Genomics Consortium, UK Biobank, FinnGen.

Language: Английский

---

Association between hs-CRP and depressive symptoms: a cross-sectional study

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: March 26, 2024

Background and aim High-sensitivity C-reactive protein (hs-CRP) is a sensitive measure of low-grade inflammation appears superior to conventional blood tests in assessing cardiovascular disease. The purpose this investigation was explore the link between high-sensitivity CRP depressive symptoms among adults. Methods results Multiple logistic regression smoothed curve fitting were used investigate association hs-CRP based on data from the, 2017-2020 National Health Nutrition Examination Survey (NHANES). Subgroup analyses interaction assess stability relationship across populations. study comprised 6,293 non-clinical participants, which included 549 individuals with symptoms. prevalence found increase increasing levels hs-CRP. This trend persisted even after quartetting levels. In fully adjusted model, each unit associated 10% odds (OR=1.10,95%CI:1.01-1.21). Participants highest quartile had 39% higher compared those lowest (OR=1.39,95%CI:1.01-1.92). Additionally, positive correlation more pronounced men. Conclusions adult Americans, there exists elevated symptoms, prominent manifestation observed males.

Language: Английский

---

Effects of genetically predicted posttraumatic stress disorder on autoimmune phenotypes

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 1, 2024

Observational studies suggest that posttraumatic stress disorder (PTSD) increases risk for various autoimmune diseases. Insights into shared biology and causal relationships between these diseases may inform intervention approaches to PTSD co-morbid conditions. We investigated the genetic contributions PTSD, 18 diseases, 3 immune/inflammatory biomarkers. Univariate MiXeR was used contrast architectures of phenotypes. Genetic correlations were estimated using linkage disequilibrium score regression. Bi-directional, two-sample Mendelian randomization (MR) performed independent, genome-wide significant single nucleotide polymorphisms; inverse variance weighted median MR estimates evaluated. Sensitivity analyses uncorrelated (MR PRESSO) correlated horizontal pleiotropy (CAUSE) also performed. considerably more polygenic (10,863 influential variants) than (median 255 variants). However, evidenced correlation with nine three inflammatory had putative effects on thyroid disease (p = 0.00009) C-reactive protein (CRP) 4.3 × 10-7). Inferences not substantially altered by sensitivity analyses. Additionally, PTSD-autoimmune association remained in multivariable analysis adjusted genetically predicted biomarkers as potential mechanistic pathway variables. No a effect (all p values > 0.05). Although models supported associations CRP, adequate explain CRP 0.18). In summary, our results overlap inflammation. has disease, consistent existing epidemiologic evidence. A previously reported is potentially confounded genetics. Together, highlight nuanced links disorders, associated signatures, importance targeting related pathways protect against disability.

Language: Английский

---

Identifying the mediating role of socioeconomic status on the relationship between schizophrenia and major depressive disorder: a Mendelian randomisation analysis

Schizophrenia, Journal Year: 2023, Volume and Issue: 9(1)

Published: Aug. 29, 2023

Depressive disorder prevalence in patients with schizophrenia has been reported to be 40%. People low socioeconomic status (SES) are more likely suffer from and major depressive (MDD). However, the causal relationship between depression potential mediating role of SES remains unclear. Two-sample Mendelian randomization (MR) analyses were conducted explore bidirectional MDD largest sample size European ancestry public genome-wide association studies (sample ranged 130,644 480,359). Inverse variance weighted (IVW) method was used as primary analysis, several canonical MR methods validation analyses. The (educational years, household income, employment status, Townsend deprivation index) estimated by two-step method. showed that genetically predicted associated an increased risk (IVW odds ratio [OR] = 1.137 [95% CI 1.095, 1.181]). Reversely, also OR 1.323 1.118, 1.565]). mediation analysis via revealed effect on partly mediated index a proportion 10.27%, but no significant found schizophrenia. These results suggest robust MDD. Patients could benefit early effective intervention index.

Language: Английский

---

Causal link between gut microbiome and schizophrenia: a Mendelian randomization study

Psychiatric Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 20, 2024

Objective Some observational studies have shown that gut microbiome is significantly changed in patients with schizophrenia. We aim to identify the genetic causal link between and Methods A two-sample Mendelian randomization (MR) study was used evaluate schizophrenia 28 microbiome-associated instrumental variants chosen from recent MR reports largest genome-wide association (8-Apr-22 release). Results Inverse variance weighted method showed genetically increased Bacteroidales_S24-7 (per SD) resulted risk of (OR = 1.110, 95% CI: [1.012–1.217], P 0.027). Similarly, Prevotellaceae promoted 1.124, [1.030–1.228], 0.009). However, Lachnospiraceae reduced 0.878, [0.785–0.983], 0.023). In addition, also suppressed by Lactobacillaceae [0.776–0.994], 0.040) Verrucomicrobiaceae 0.860, [0.749–0.987], 0.032). Finally, we did not find any significant results other 23 Conclusion Our analysis suggests promotes risk, whereas Lachnospiraceae, Lactobacillaceae, reduces risk. Thus, regulation disturbed intestinal microbiota may represent a new therapeutic strategy for

Language: Английский

---