Correlation between polygenic risk scores of depression and cortical morphology networks

Journal of Psychiatry and Neuroscience, Год журнала: 2025, Номер 50(1), С. E21 - E30

Опубликована: Янв. 3, 2025

Background:

Cortical morphometry is an intermediate phenotype that closely related to the genetics and onset of major depressive disorder (MDD), cortical morphometric networks are considered more relevant disease mechanisms than brain regions. We sought investigate changes in MDD their relationship with genetic risk healthy controls.

Methods:

recruited controls patients Han Chinese descent. Participants underwent DNA extraction magnetic resonance imaging, including T₁-weighted diffusion tensor imaging. calculated polygenic scores (PRS) based on previous summary statistics from a genome-wide association study population. used novel method Kullback–Leibler divergence construct inverse (MIND) network, we included classic similarity network (MSN) as complementary approach. Considering between white matter networks, also constructed streamlined density network. conducted group comparison PRS correlation analyses at both regional level.

Results:

130 195 MDD. The results indicated enhanced connectivity MIND among people high risk, particularly somatomotor (SMN) default mode (DMN). did not observe significant findings MSN. showed disruption primarily SMN DMN. outperformed MSN distinguishing status.

Limitations:

Our was cross-sectional could explore causal relationships morphological changes, connectivity, states. Some had received antidepressant treatment, which may have influenced morphology structure.

Conclusion:

depression be disintegration, associated decoupling These provide new insights into potential biomarkers

Язык: Английский

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The impact of cortical and subcortical volumes on major depression risk: A genetic study

Journal of Affective Disorders, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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White‐Matter Structural Connectivity and Alzheimer's Disease: A Mendelian Randomization Study

Brain and Behavior, Год журнала: 2025, Номер 15(2)

Опубликована: Фев. 1, 2025

ABSTRACT Background Alzheimer's disease (AD) and white‐matter structural connectivity have been linked in some observational studies, although it is unknown if this a causal relationship. The purpose of study was to examine the impact various on AD via two‐sample multivariate Mendelian randomization (MR) approach. Methods genome‐wide association (GWAS) Wainberg et al. provided summary data connectivity, Bellenguez al.’s GWAS aggregated for AD. MR methods included inverse variance weighted, Egger, simple mode, weighted median, mode. Heterogeneity, horizontal pleiotropy, “leave‐one‐out” analysis guaranteed robustness causation. Finally, reverse conducted that showed positive results forward analysis. Results Among 206 connections, we identified 10 connections were strongly correlated with genetic susceptibility Right‐hemisphere limbic network thalamus salience_ventral attention accumbens positively likelihood AD, while remaining 8 negatively related None above relationship Conclusion Our reveals certain degree between which may provide support future diagnosis treatment

Язык: Английский

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Subjective Well-being: A Key to Bridge Urbanization, Brain and Mental Health

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Фев. 10, 2025

The pursuit of happiness is a lifelong endeavor for everyone; nevertheless, elucidating its etiology, neurobiological substrates, and implications mental health continues to pose significant challenges in contemporary research. This study sought delineate the causal relationships among subjective well-being (SWB), urbanization, brain, health, explore protective role SWB against prevalent psychiatric disorders. Utilizing data from 198,823 adults UK Biobank, including questionnaires (five items), urban living environments (121 variables), neuroimaging (2,413 measures), assessments (39 indicators), ICD-10 diagnoses (10 disorders), we initially identified two robust components using ten-fold cross-validated factor analysis: internal (ISWB) social (SSWB). Phenome-wide association studies (PheWAS) revealed associations between urbanization variables both ISWB (78/121) SSWB (59/121); indicators (416/2,413 measures) (77/2,413); (38/39 indicators) (37/39) (P < 0.05, Bonferroni corrected). Sequential mediation analysis uncovered 28 pathways brain (ISWB: 16 pathways, SSWB: 12 pathways), while moderated 19 where significantly → (14 ISWB, 5 SSWB). Finally, Cox proportional hazards survival demonstrated that individuals highest sextile had 76% reduction overall risk developing 10 disorders compared with those lowest (Z = -29.49, Hazard Ratio [HR] 0.24, P 3.93e-191), showed 36% -9.42, HR 0.64, 4.50e-2). Moreover, effects depression 0.13, 0.39). By systematically uncovering through which differentially participate regulation on human thereby affecting this thus provides biological evidence modifiable prevention common

Язык: Английский

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Mendelian randomization analyses uncover causal relationships between brain structural connectome and risk of psychiatric disorders

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 21, 2025

Abstract Growing evidence suggests abnormalities of brain structural connectome in psychiatric disorders, but the causal relationships remain underexplored. We conducted bidirectional two-sample Mendelian randomization (MR) analyses to investigate links between 206 white-matter connectivity phenotypes (n = 26,333, UK Biobank) and 13 major disorders 14,307 1,222,882). Forward MR identified effects genetically predicted five on six with associations being significant or suggestive. For instance, left-hemisphere frontoparietal control network right-hemisphere default mode was significantly negatively associated autism spectrum disorder risk, while increased hippocampus linked decreased anorexia nervosa cannabis use risk. Reverse revealed suggestively risk two four different phenotypes. example, susceptibility found be visual pallidum. These findings offer new insights into etiology highlight potential biomarkers for early detection prevention at level.

Язык: Английский

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The role of the hippocampus and SLC39A8 in chronic musculoskeletal pain-induced dementia: a Mendelian randomization study

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 16, 2025

Despite observational studies suggesting a link between chronic musculoskeletal pain (CMP) and increased risk of cognitive decline dementia, the causal nature this relationship remains uncertain due to potential confounding factors reverse causality. We employed two-sample Mendelian Randomization (TSMR), bidirectional MR, mediation drug-target colocalization analysis, along with gene set enrichment protein-protein interaction (PPI) analyses. TSMR assessed associations CMP dementia its subtypes, including Alzheimer's disease (AD), vascular (VaD), Lewy body (LBD), frontotemporal (FTD), Parkinson's (PD). Bidirectional MR evaluated causality, while analyses identified mediators, focusing on neuroimaging phenotypes. Drug-target investigated role SLC39A8 gene, analysis determined shared genetic variants. Gene PPI elucidated biological pathways implicated in CMP-dementia relationship. Robust evidence established low back (LBP) PD, knee osteoarthritis as partial mediator, pathway involving inflammation. revealed no further supporting unidirectional from LBP PD. Colocalization confirmed distinct architectures for mediator. highlighted critical pathways, such purine metabolism glutamate receptor signaling. Suggestive indicated links limb overall myalgia VaD, well protective effects Polymyalgia Rheumatica (PMR) against AD rheumatism This study reveals complex neurodegenerative diseases, particularly robust The findings underscore need research elucidate underlying mechanisms inform targeted prevention treatment strategies.

Язык: Английский

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Response to commentaries by Schmidt and Kaplan, Penhune, Hickok and Theofanopoulou on “Beat-based dancing to music has evolutionary foundations in advanced vocal learning.”

BMC Neuroscience, Год журнала: 2024, Номер 25(1)

Опубликована: Ноя. 6, 2024

Abstract Each commentary on my article raises important points and new ideas for research rhythmic processing in humans other species. Here I respond to concerning the role of social factors ontogeny beat synchronization, neural connectivity underlying evolution this connectivity, mechanisms by which evolutionary changes strength one white matter tract (driven natural selection) can have knock-on effects structure an adjacent tract.

Язык: Английский

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Beyond Volume: Unraveling the Genetics of Human Brain Geometry

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 25, 2024

Abstract Brain geometry impacts brain function. A quantitative encoding of form is provided by the Laplace-Beltrami operator’s spectrum eigenvalues (LBS). We examined LBS genetics 22 subcortical structures including cerebellum in 19,862 healthy White-British UK Biobank participants multivariate GWAS (MOSTest) on first 49 each. Controlling for surface and volume, we identified 80 unique variants (p<1/22*5E-8) influencing shapes one or several structures, with highest yield (37 variants) stem. The previously known influence these loci basic morphology, such as thus shown to also complex shape. Known associations observed blood pressure, neurodegeneration, alcohol consumption, mental disorders hint at preclinical stages conditions potentially mediating genetic effect morphology. Significant correlations between polygenic risks hypertension, ischemic stroke schizophrenia evince early biomarkers.

Язык: Английский

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Uncovering the multivariate genetic architecture of frailty with genomic structural equation modelling

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 24, 2024

Frailty is a multifaceted clinical state associated with accelerated aging and adverse health outcomes. Informed etiological models of frailty hold promise for producing widespread improvements across the population. currently measured using aggregate scores, which obscure pathways that are only relevant to subcomponents frailty. Therefore, we performed first multivariate genome-wide association study latent genetic architecture between 30 deficits, identified 408 genomic risk loci. Our model included general factor overlap all plus six novel factors indexing shared signal specific groups deficits. Follow-up analyses demonstrated added value factors, including predicting in external datasets, divergent correlations clinically outcomes, unique underlying biology linked aging. This suggests nuanced key understanding its causes how it relates worse health.

Язык: Английский

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Genetic factors and symptom dimensions associated with antidepressant treatment outcomes: clues for new potential therapeutic targets?

European Archives of Psychiatry and Clinical Neuroscience, Год журнала: 2024, Номер unknown

Опубликована: Авг. 27, 2024

Abstract Treatment response and resistance in major depressive disorder (MDD) show a significant genetic component, but previous studies had limited power also due to MDD heterogeneity. This literature review focuses on the factors associated with treatment outcomes MDD, exploring their overlap those clinically relevant symptom dimensions. We searched PubMed for: (1) genome-wide association (GWASs) or whole exome sequencing (WESs) that investigated efficacy MDD; (2) examining between specific dimensions; (3) GWASs of identified 13 one WES reporting several loci, genes, gene sets involved expression, immune system regulation, synaptic transmission plasticity, neurogenesis differentiation. Nine dimensions were poor studied by (anxiety, neuroticism, anhedonia, cognitive functioning, melancholia, suicide attempt, psychosis, sleep, sociability). Four genes both these dimensions: CGREF1 (anxiety); MCHR1 (neuroticism); FTO NRXN3 (sleep). Other overlapping signals found when considering suggestively outcomes. Genetic showed convergence at level biological processes, despite no replication variant level. The interest may point shared mechanisms potential targets for new treatments tailored individual patient’s clinical profile.

Язык: Английский

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