TGR5-mediated lateral hypothalamus-dCA3-dorsolateral septum circuit regulates depressive-like behavior in male mice

Neuron, Journal Year: 2024, Volume and Issue: 112(11), P. 1795 - 1814.e10

Published: March 21, 2024

Language: Английский

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Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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

Twin Research and Human Genetics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 20

Published: Jan. 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.

Language: Английский

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How to Use the Cuprizone Model to Study De- and Remyelination

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1445 - 1445

Published: Jan. 24, 2024

Multiple sclerosis (MS) is an autoimmune and inflammatory disorder affecting the central nervous system whose cause still largely unknown. Oligodendrocyte degeneration results in demyelination of axons, which can eventually be repaired by a mechanism called remyelination. Prevention pharmacological support remyelination are two promising strategies to ameliorate disease progression MS patients. The cuprizone model commonly employed investigate oligodendrocyte mechanisms or explore pathways. During last decades, several different protocols have been applied, all their pros cons. This article intends offer guidance for conducting pre-clinical trials using mice, focusing on discovering new treatment approaches prevent enhance

Language: Английский

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Gene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study

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

Published: Sept. 18, 2024

Language: Английский

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Genome-wide association study identifies 30 obsessive-compulsive disorder associated loci

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 13, 2024

Obsessive-compulsive disorder (OCD) affects ~1% of the population and exhibits a high SNP-heritability, yet previous genome-wide association studies (GWAS) have provided limited information on genetic etiology underlying biological mechanisms disorder. We conducted GWAS meta-analysis combining 53,660 OCD cases 2,044,417 controls from 28 European-ancestry cohorts revealing 30 independent significant SNPs SNP-based heritability 6.7%. Separate for clinical, biobank, comorbid, self-report sub-groups found no evidence sample ascertainment impacting our results. Functional positional QTL gene-based approaches identified 249 candidate risk genes OCD, which 25 were as putatively causal, highlighting WDR6, DALRD3, CTNND1 in MHC region. Tissue single-cell enrichment analyses highlighted hippocampal cortical excitatory neurons, along with D1- D2-type dopamine receptor-containing medium spiny playing role risk. displayed correlations 65 out 112 examined phenotypes. Notably, it showed positive all included psychiatric phenotypes, particular anxiety, depression, anorexia nervosa, Tourette syndrome, negative subset autoimmune disorders, educational attainment, body mass index.. This study marks step toward unraveling its landscape advances understanding genetics, providing foundation future interventions to address this debilitating

Language: Английский

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Distinct biological signature and modifiable risk factors underlie the comorbidity between major depressive disorder and cardiovascular disease

Nature Cardiovascular Research, Journal Year: 2024, Volume and Issue: 3(6), P. 754 - 769

Published: June 17, 2024

Language: Английский

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Leveraging haplotype information in heritability estimation and polygenic prediction

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Polygenic prediction has yet to make a major clinical breakthrough in precision medicine and psychiatry, where the application of polygenic risk scores is expected improve decision-making. Most widely used approaches for estimating are based on summary statistics from external large-scale genome-wide association studies, which rely assumptions matching data distributions. This may hinder impact modern diverse populations due small differences genetic architectures. Reference-free estimators instead genomic best linear unbiased predictions model population interest directly. We introduce framework, named hapla, with novel algorithm clustering haplotypes phased genotype estimate heritability perform reference-free complex traits. utilize inferred haplotype clusters compute accurate estimates simulation study iPSYCH2012 case-cohort depression disorders schizophrenia. demonstrate that our haplotype-based approach robustly outperforms standard genotype-based approaches, can help pave way future psychiatry. Here authors develop framework leverage information through estimation prediction. Their disease more accurately than existing methods, paving advancements personalized medicine.

Language: Английский

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From air to mind: unraveling the impact of indoor pollutants on psychiatric disorders

Frontiers in Psychiatry, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

Epidemiological evidence from the past 20 years indicates that environmental chemicals brought into air by vaporization of volatile organic compounds and other anthropogenic pollutants might be involved, at least in part, development or progression psychiatric disorders. This comes primarily occupational work studies humans, with indoor occupations being most important sources airborne affecting neural circuits implicated mood disorders (e.g., major depressive disorder bipolar disorder). The current mini review brings together recent findings pollution different fields research, including genetics, neuropathology, neuroimaging, for gauging underlying physiological mechanisms leading to emotional disturbances impact nearly all aspects human behavior. A better understanding how affect brain neurons augment clinical symptoms associated will undoubtedly useful subsequent treatment patients and/or article is part themed issue, "Understanding Link Between Environmental Pollutants, Brain & Behavior."

Language: Английский

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Integrating genetics and transcriptomics to characterize shared mechanisms in digestive diseases and psychiatric disorders

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 14, 2025

Digestive and psychiatric disorders tend to co-occur, yet mechanisms remain unclear. Leveraging genetic transcriptomic data integration, we conduct multi-trait analysis of GWAS (MTAG) weighted gene co-expression network (WGCNA) explore shared mechanism between gastrointestinal disorders. Significant correlations were found these disorders, especially in irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), depression (DEP), neuroticism (NE). MTAG identify 60 novel pleiotropic loci for IBS 14 GERD, predominantly located near genes associated with neurological pathways. Further WGCNA identifies multiple modules enriched involved pathways digestive tissues, some strongly preserved across brain tissues. Moreover, our suggests BSN, CELF4, NRXN1 as central players the regulation gut-brain axis (GBA). This study enhances understanding GBA underscores crucial targets future research. Genetics transcriptomics reveal highlighting loci. Genes regulate axis, revealing potential therapeutic targets.

Language: Английский

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