Directional Selection and Evolution of Polygenic Traits in Eastern Eurasia: Insights from Ancient DNA

Twin Research and Human Genetics, Год журнала: 2025, Номер unknown, С. 1 - 20

Опубликована: Янв. 30, 2025

Abstract This study explores directional selection on physical and psychosocial phenotypes in Eastern Eurasian populations, utilizing a dataset of 1245 ancient genomes. By analyzing polygenic scores (PGS) for traits including height, educational attainment (EA), IQ, autism, schizophrenia, others, we observed significant temporal trends spanning the Holocene era. The results suggest positive cognitive-related such as EA autism spectrum disorder (ASD), alongside negative anxiety depression. height were mixed showed nonlinear relationships with Years Before Present (BP). These partially mediated by genetic components linked to distinct ancestral populations. Regression models incorporating admixture, geography, variables used account biases population composition over time. Latitude effect ASD PGS, while it had skin pigmentation scores. Additionally, latitude exhibited effects multiple phenotypes. patterns highlight influence climate-mediated pressures trait evolution. Spline regression revealed that several years BP. findings provide evidence complex evolutionary dynamics, selective shaping phenotypic diversity across different timescales environments.

Язык: Английский

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From Clinic to Mechanisms: Multi-Omics Provide New Insights into Cerebrospinal Fluid Metabolites and the Spectrum of Psychiatric Disorders

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Март 14, 2025

Язык: Английский

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Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling

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

Опубликована: Июль 5, 2024

Abstract The major anxiety disorders (ANX; including generalized disorder, panic and phobias ) are highly prevalent, often onset early, persist throughout life, cause substantial global disability. Although distinct in their clinical presentations, they likely represent differential expressions of a dysregulated threat-response system. Here we present genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases 729,881 controls. We identified 58 independent significant risk variants 66 genes with robust biological support. In an sample 1,175,012 self-report 1,956,379 controls, 51 the associated were replicated. As predicted by twin studies, found genetic correlation between depression, neuroticism, other internalizing phenotypes. Follow-up analyses demonstrated enrichment all brain regions highlighted GABAergic signaling as one potential mechanism underlying risk. These results advance our understanding architecture prioritize for functional follow-up studies.

Язык: Английский

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Genome-Wide Insights into Internalizing Symptoms in Admixed Latin American Children

Genes, Год журнала: 2025, Номер 16(1), С. 63 - 63

Опубликована: Янв. 8, 2025

Background/Objectives: Internalizing disorders, including depression and anxiety, are major contributors to the global burden of disease. While genetic architecture these disorders in adults has been extensively studied, their early-life mechanisms remain underexplored, especially non-European populations. This study investigated underlying internalizing symptoms a cohort Latin American children. Methods: included 1244 Brazilian children whose legal guardians completed Child Behavior Checklist (CBCL) questionnaire. Genotyping was performed using Illumina HumanOmni 2.5-8v1 BeadChip. Results: The genome-wide association analysis revealed significant rs7196970 (p = 4.5 × 10−8, OR 0.61), ABCC1 gene, with symptoms. Functional annotation highlighted variants epigenetically active regulatory regions, multiple linked differential expression across several human tissues. Pathway enrichment identified 42 pathways, notable involvement neurobiological processes such as glutamatergic, GABAergic, dopaminergic synapses. Conclusions: identifies novel factors potentially associated These results may contribute future research on targeted interventions for childhood conditions.

Язык: Английский

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Sex-specific differences in peripheral blood metabolites and biological functions in major depressive disorder: a systematic review and meta-analysis

Neuroscience & Biobehavioral Reviews, Год журнала: 2025, Номер 170, С. 106052 - 106052

Опубликована: Фев. 5, 2025

Язык: Английский

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Integrating HiTOP and RDoC Frameworks Part II: Shared and Distinct Biological Mechanisms of Externalizing and Internalizing Psychopathology

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

Опубликована: Фев. 6, 2025

Abstract Background The Hierarchical Taxonomy of Psychopathology (HiTOP) and Research Domain Criteria (RDoC) frameworks emphasize transdiagnostic mechanistic aspects psychopathology, respectively. We used a multi-omics approach to examine how externalizing (EXT), internalizing (INT), shared EXT+INT liability map onto these models. Methods conducted analyses across five RDoC units analysis: genes, molecules, cells, circuits, physiology. Using genome-wide association studies from the companion Part I article, we identified genes tissue-specific expression patterns. drug repurposing that integrate gene annotations identify potential therapeutic targets single-cell RNA sequencing data implicate brain cell types. then magnetic resonance imaging regions circuits associated with each psychopathology spectrum. Finally, tested causal relationships between spectrum physical health conditions. Results identification methods, EXT was 1,759 INT 454 1,138 genes. Drug targets, including those affect dopamine serotonin pathways. Expression enriched in GABAergic, cortical, hippocampal neurons, while were more narrowly linked GABAergic neurons. reduced gray matter volume amygdala subcallosal cortex. Mendelian randomization, showed stronger effects on health—including chronic pain cardiovascular diseases—than EXT. Conclusions Our findings revealed distinct pathways underlying psychopathology. Integrating genomic insights HiTOP advanced our understanding mechanisms underlie

Язык: Английский

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Association between polygenic risk scores and treatment response to antidepressants, benzodiazepines, and antihistamines in anxiety and depression

Biological Psychiatry Global Open Science, Год журнала: 2025, Номер unknown, С. 100470 - 100470

Опубликована: Фев. 1, 2025

Язык: Английский

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Computer reconstruction of gene networks controlling anxiety levels in humans and laboratory mice

Vavilov Journal of Genetics and Breeding, Год журнала: 2025, Номер 29(1), С. 162 - 170

Опубликована: Март 4, 2025

Anxiety is a normotypic human condition, and like any other emotion has an adaptive value. But excessively high or low anxiety negative consequences for adaptation, which primarily determines the importance of studying these two extreme conditions. At same time, it known that perception aversive stimuli associated with leads to changes in activity brain’s cingulate cortex. The advantage animals as models genetic bases humans ability subtly control external conditions formation certain state, availability brain tissues, create study transgenic models, including through use differentially expressed genes small laboratory from family Muridae anxiety. Within framework translational approach, three-domain potential gene network, generalized humans, was reconstructed using mouse different levels by automatically analyzing texts scientific articles. One domain reduced second increased anxiety, third dispatcher who activates one domains depending on status organism (genetic, epigenetic, physiological). Stages work: (I) A list cortex wild type CD-1 line NCBI GEO database (experiment GSE29014). Using tools this database, differences expression were revealed groups mice (relatively normal) (II) Search orthologs DEG OMA Orthology database. (III) Computer reconstruction ANDSystem cognitive system based (a) orthologous stage (III), (b) MalaCards proven methods approach networks behavior regulation can be used identify molecular markers personality traits, propensity psychopathology.

Язык: Английский

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Evaluation of the two-way associations between mental disorders and menstrual irregularities: A Mendelian randomization study from both directions

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

Опубликована: Март 1, 2025

Язык: Английский

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Heritability and polygenic load for comorbid anxiety and depression

Translational Psychiatry, Год журнала: 2025, Номер 15(1)

Опубликована: Март 26, 2025

Abstract Anxiety and depression commonly occur together resulting in worse health outcomes than when they isolation. We aimed to determine whether the genetic liability for comorbid anxiety was greater or occurred alone. Data from 12,792 genotyped twins (ages 38–85) were analysed, including 1,986 complete monozygotic 1,594 dizygotic pairs. Outcomes prescription of antidepressant anxiolytic drugs, as defined by World Health Organization Anatomical Therapeutic Chemical Classification System (ATC) convention, ( n = 1028), only 718), 484). Heritability each outcome estimated using twin modelling, influence common variation assessed polygenic scores (PGS) depressive symptoms, anxiety, 40 other traits. 79% compared with 41% 50% The PGS symptoms likewise predicted more (adjusted odds ratio per SD 1.53, 95% CI 1.43–1.63; Δ R 2 0.031, ΔAUC 0.044) outcomes, nearly identical results International Diseases (ICD) diagnoses 1.70, 1.53–1.90; 0.036, 0.051). Individuals highest decile had over 5 times higher being prescribed medication those lowest decile. While on a predominant role may have been biased size heterogeneity available data bases, are consistent conclusion that factors explain substantially

Язык: Английский

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