Genetics of migraine: complexity, implications, and potential clinical applications

The Lancet Neurology, Journal Year: 2024, Volume and Issue: 23(4), P. 429 - 446

Published: March 18, 2024

Language: Английский

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Phenome-wide investigation of bidirectional causal relationships between major depressive disorder and common human diseases

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

Published: Dec. 27, 2024

The high comorbidity of major depressive disorder (MDD) with other diseases has been well-documented. However, the pairwise causal connections for MDD comorbid networks are poorly characterized. We performed Phenome-wide Mendelian randomization (MR) analyses to explore bidirectional associations between (N = 807,553) and 877 common from FinnGen datasets 377,277). inverse variance weighting method was primary technique, methods (weighted median MR-Egger) were used sensitivity analyses. Our MR showed that genetic liability is causally associated risks 324 disease phenotypes (average b: 0.339), including 46 psychiatric behavioral disorders 0.618), 18 neurological 0.348), 44 respiratory 0.345), 40 digestive 0.281), circulatory 0.237), 37 genitourinary 0.271), 66 musculoskeletal connective 0.326), 22 endocrine 0.302), others. In a reverse analysis, total 51 components predisposing various risk 0.086), 5 infectious 0.056), 11 0.106), 14 oncological 0.108), 0.114). Bidirectional identified 15 diseases. For most analyses, little evidence heterogeneity pleiotropy detected. findings confirmed extensive significant role predisposition in contributing human phenotypes, which more pronounced than those seen analysis influences on MDD.

Language: Английский

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Causal associations of inflammatory cytokines and urinary stones: a two-sample Mendelian randomization study

Translational Andrology and Urology, Journal Year: 2025, Volume and Issue: 14(2), P. 258 - 265

Published: Feb. 1, 2025

Prior research has shown potential changes in cytokine and growth factor levels patients with urinary stones, but the causal relationship remains uncertain. The purpose of this study was to investigate between tract stones. This used a two-sample Mendelian randomization (MR) 41 circulating cytokines factors datasets alongside stone disease (USD) data. It employed various analytical methods including inverse variance weighted (IVW) analysis, maximum likelihood estimation, MR-Egger regression, median approach, simple method, mode establish relationships. Sensitivity analysis included regression intercept test Cochrane's Q statistic. Using IVW an increase stem cell β associated decreased risk [odds ratio (OR) =0.9990; 95% confidence interval (CI): 0.9980-0.9999; P=0.04]. Conversely, interleukin-18 elevated stones (OR =1.0012; CI: 1.0002-1.0022; P=0.01). Various consistently supported these findings. Our findings suggest unidirectional interleukin-18, factors, USD. indicates that may actively contribute development or prevention USD, offering new avenue for clinical intervention based on modulation.

Language: Английский

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Major depressive disorder in sub-Saharan Africa: findings from the Neuro-GAP-Psychosis study

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Major depressive disorder (MDD) is a significant contributor to the burden of mental disorders in Africa, necessitating an understanding its prevalence and risk factors across diverse socio-cultural contexts address health disparities improve care. This cross-sectional study analyzed 7,073 adult participants from hospital settings Uganda, Kenya, Ethiopia, South Africa within NeuroGAP-Psychosis study. Prevalence estimates, calculated with 95% confidence intervals, revealed overall rates 0.9% for current MDD 5.1% lifetime MDD, reporting highest (2.1% current, 8.4% lifetime). Multilevel logistic regression identified associations between negative life events, alcohol use, Kessler psychological distress scores, while was linked age, female sex, chronic pain, frequent headaches, positive psychosis screening. These findings underscore need targeted interventions tailored reduce studied populations.

Language: Английский

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NEK4: prediction of available drug targets and common genetic linkages in bipolar disorder and major depressive disorder

Frontiers in Psychiatry, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 30, 2025

Background Bipolar disorder (BD) is a mental illness characterized by alternating episodes of elevated mood and depression, while major depressive (MDD) debilitating condition that ranks second globally in terms disease burden. Pharmacotherapy plays crucial role managing both BD MDD. We investigated the genetic differences populations individuals with MDD BD, from perspective, we offered new insights into potential drug targets. This will provide clues to Methods study employed genome-wide association studies (GWAS) summary-data-based Mendelian randomization (SMR) methods investigate underpinnings patients bipolar predict target genes. Genetic variants associated were identified through large-scale GWAS datasets. For utilized comprehensive meta-analysis comprising 57 cohorts Europe, North America, Australia, including 41,917 cases 371,549 controls European ancestry. dataset included type 1 2 diagnosed based on DSM-IV, ICD-9, or ICD-10 criteria standardized assessments. MDD, used data Howard DM et al., which integrated largest totaling 246,363 561,190 controls. The SMR approach, combined expression quantitative trait loci (eQTL) data, was then applied assess causal associations between these gene expression, aiming identify markers targets Furthermore, two-sample (TSMR) analyses performed explore links protein (pQTL) disorders. Results analysis revealed 41 druggable genes five appeared brain tissue blood eQTL datasets significantly risk. 45 found be analysis, three simultaneously NEK4 , common candidate for also high risk diseases may help differentiate BD. Specifically, showed strong (β brain=0.126, P FDR=0.001; βblood=1.158, FDR=0.003) brain=0.0316, FDR=0.022; βblood=0.254, FDR=0.045). Additionally, notably linked (βbrain=0.123, FDR=2.97E-05; βblood=1.018, FDR=0.002), but no significant 2.Moreover, TSMR four proteins (BMP1, F9, ITIH3, SIGIRR) affecting PSMB4 Conclusion Our as key (MDD), suggesting its biomarker differentiating subtypes. Using GWAS, SMR, approaches, multiple risk, providing basis These findings offer promising directions precision medicine novel therapeutic strategies health treatment.

Language: Английский

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Fremanezumab for the Treatment of Patients With Migraine and Comorbid Major Depressive Disorder

JAMA Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: May 5, 2025

Importance Migraine and major depressive disorder are frequently comorbid; however, evidence evaluating the efficacy of preventive migraine therapy in patients with both diseases is limited. Objective To evaluate safety fremanezumab adults comorbid disorder. Design, Setting, Participants The UNITE study was a double-blind, placebo-controlled, parallel-group, randomized clinical trial consisting 4-week screening period, 12-week double-blind open-label extension (OLE), conducted between July 9, 2020, August 31, 2022. at 55 centers across 12 countries. Eligible were episodic (EM) or chronic (CM), history according to Diagnostic Statistical Manual Mental Disorders (Fifth Edition) criteria for more months before screening, active symptoms depression (9-item Patient Health Questionnaire score 10 more) screening. Interventions Patients 1:1 receive monthly (225 mg) matched placebo. All OLE received quarterly (675 mg). Main Outcomes Measures primary end point mean change from baseline days during period. Results Of 540 screened study, 353 (mean [SD] age, 42.9 [12.3] years; 310 female [88%]; EM, 48%; CM, 52%) eligible (n = 175) placebo 178). Mean (SE) period −5.1 (0.50; 95% CI, −6.09 −4.13) −2.9 (0.49; −3.89 −1.96) ( P <.001). Hamilton Depression Rating Scale–17 Items week 8 −6.0 (0.55; −7.10 −4.95) −4.6 (0.54; −5.66 −3.55) (least squares [SE] difference: −1.4 [0.61]; −2.61 −0.22; .02). Adverse events consistent other trials. maintained throughout OLE. Conclusions Relevance Treatment compared resulted significant reductions symptoms. No new concerns observed. authors’ knowledge, this first trial, specifically designed assess disorder, demonstrate improvements single pharmacological intervention. Trial Registration ClinicalTrials.gov Identifier: NCT04041284

Language: Английский

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Association between TRP channels and glutamatergic synapse gene polymorphisms and migraine and the comorbidities anxiety and depression in a Chinese population

Frontiers in Genetics, Journal Year: 2023, Volume and Issue: 14

Published: May 26, 2023

Background: Genetic and environmental factors contribute to migraine the comorbidities of anxiety depression. However, association between genetic polymorphisms in transient receptor potential (TRP) channels glutamatergic synapse genes with risk depression remain unclear. Methods: 251 patients containing 49 112 600 controls were recruited. A customized 48-plex SNPscan kit was used for genotyping 13 SNPs nine target genes. Logistic regression conducted analyze these SNPs’ susceptibility comorbidities. The generalized multifactor dimension reduction (GMDR) applied SNP-SNP gene-environment interactions. GTEx database examine effects significant on gene expressions. Results: TRPV1 rs8065080 TRPV3 rs7217270 associated an increased dominant model [OR adj (95% CI): 1.75 (1.09–2.90), p = 0.025; 1.63 (1.02–2.58), 0.039, respectively]. GRIK2 rs2227283 edge significance CI) 1.36 (0.99–1.89), 0.062]. In patients, rs222741 both recessive 2.64 (1.24–5.73), 0.012; 1.97 (1.02–3.85), 0.046, TRPM8 rs7577262 (OR 0.27, 95% CI 0.10–0.76, 0.011). TRPV4 rs3742037, rs17862920 SLC17A8 rs11110359 2.03 (1.06–3.96), 0.035; 0.48 (0.23–0.96), 0.042; 0.42 (0.20–0.84), 0.016, Significant eQTL sQTL signals observed SNP rs8065080. Individuals GRS (Genetic scores) Q4 (14–17) had a higher lower comorbidity than those scores Q1 (0–9) groups 2.31 (1.39–3.86), 0.001; 0.28 (0.08–0.88), 0.034, Conclusion: This study suggests that rs8065080, rs7217270, polymorphism may associate risk. rs222741, rs17862920, Higher increase decrease

Language: Английский

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Anxiety disorders and adhesive capsulitis: a bidirectional Mendelian randomization study

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

Previous epidemiological investigations and related research efforts consistently have outlined an observable association between anxiety disorders adhesive capsulitis (AC). However, the intricate nature of causal connection these entities has yet to be fully clarified. Therefore, this investigative study aims thoroughly examine delineate interrelationship AC using a bidirectional, two-sample Mendelian randomization (MR) approach.

Language: Английский

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No causal association between allergic rhinitis and migraine: a Mendelian randomization study

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: Jan. 27, 2024

Allergic rhinitis (AR) and migraine are among the most common public health problems worldwide. Observational studies on correlation between AR have reported inconsistent results. This study aimed to investigate causal relationship of with its subtypes, including aura (MA) without (MO). Bidirectional two-sample Mendelian randomization (MR) analysis was performed publicly available summary-level statistics large genome-wide association estimate possible effects. The inverse variance-weighted method selected for primary supplemented weighted median, mode, MR-Egger methods. using summary effect estimates (CAUSE) were further verify causality. Several sensitivity tests, leave-one-out, Cochran's Q, intercept, MR-PRESSO assess robustness did not exhibit a significant elevated risk any (odd ratio (OR), 0.816; 95% confidence interval (CI), 0.511-1.302; P = 0.394), MA (OR, 0.690; CI 0.298-1.593; 0.384), or MO 1.022; 0.490-2.131; 0.954). Consistently, reverse MR reveal effects subtypes AR. Almost all analyses supported clear risk. More research is warranted complex migraine.

Language: Английский

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Effect of genetic liability to migraine and its subtypes on breast cancer: a mendelian randomization study

BMC Cancer, Journal Year: 2023, Volume and Issue: 23(1)

Published: Sept. 20, 2023

Abstract Background The relationship between migraine and breast cancer risk has generated conflicting findings. We attempted to assess the association using Mendelian randomization (MR) analysis. Methods selected genetic instruments associated with from a recently published genome-wide studies (GWAS). Inverse variant weighted (IVW) analysis was adopted as main method, we also performed weighted-median method MR‒Egger, MR pleiotropy residual sum outlier (MR-PRESSO), Robust Adjusted Profile Score (MR-RAPS) methods supplements. Results Our suggested that any (AM) factor for overall (IVW: odds ratio (OR) = 1.072, 95% confidence intervals (CI) 1.035–1.110, P 8.78 × 10 − 5 , false discovery rate (FDR) 7.36 4 ) estrogen receptor-positive (ER+) OR 1.066, CI 1.023–1.111, 0.0024; FDR 0.0108) but not receptor-negative (ER-) cancer. In its subtype analysis, women history of without aura (MO) had an increased ER- 1.089, 1.019–1.163, 0.0118, 0.0354), MO suggestively ( > 0.05 IVW < 0.05). No significant heterogeneity or horizontal found in sensitivity Conclusion This study AM have ER +

Language: Английский

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