The genetic architecture of cortical similarity networks DOI Creative Commons
Isaac Sebenius,

Varun Warrier,

Richard A.I. Bethlehem

et al.

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

Published: Dec. 21, 2024

Abstract The genetic architecture of human brain networks is central to understanding the organization and evolution cortex, causal relationships between structure function, pathogenesis heritable neuropsychiatric disorders. However, current genetics remains fragmented. Here, we investigated common effects on Morphometric INverse Divergence (MIND), a biologically-validated, heritable, multimodal MRI metric inter-areal similarity connectivity. Using discovery dataset (N > 30,000 adults), estimated subject-specific MIND from multivariate distributions four features at each 23 cortical areas performed genome-wide association studies (GWAS) 276 edges. These edge-level were highly replicated by parallel GWAS an independent validation 18,000 adults). We found that strong correlations multiple edges largely reducible two gradients genetically-determined similarity, which was aligned with geodesic distance one phylogenetically primitive (paleocortex archicortex) predicted dual origin theory evolution. Genetic more than comparable derived functional connectivity networks; paleocortical trend genetically correlated with, causally predictive of, Finally, identified global local both nine clinical diagnoses or biomedical traits, indicating normative pleiotropically associated inherited risk disorders systemic metabolic immune traits. results provide fresh insight into origins cortex their implications for function health.

Language: Английский

Structural MRI of brain similarity networks DOI
Isaac Sebenius, Lena Dorfschmidt, Jakob Seidlitz

et al.

Nature reviews. Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 28, 2024

Language: Английский

Citations

8
Genome-wide and phenome-wide studies provided insights into brain glymphatic system function and its clinical associations DOI Creative Commons
Lusen Ran,

Yuanyuan Fang,

Chang Cheng

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(3)

Published: Jan. 17, 2025

We applied an MRI technique diffusion tensor imaging along the perivascular space (DTI-ALPS) for assessing glymphatic system (GS) in a genome-wide association study (GWAS) and phenome-wide (PheWAS) of 40,486 European individuals. Exploratory analysis revealed 17 genetic loci significantly associating with regional DTI-ALPS index. found 58 genes, including SPPL2C EFCAB5 , which prioritized index subtypes associated neurodegenerative diseases. PheWAS 241 traits suggested that body mass blood pressure phenotypes closely related to GS function. Moreover, we detected disrupted function 44 625 predefined disease conditions. Notably, Mendelian randomization mediation indicated lower was risk factor ischemic stroke (odds ratio = 1.56, P 0.028) by partly mediating obesity. Results provide insights into architecture mechanism DIT-ALPS highlight its great clinical value, especially cerebral stroke.

Language: Английский

Citations

1
Polygenic scores for autism are associated with reduced neurite density in adults and children from the general population DOI Creative Commons
Yuanjun Gu, Eva-Maria Stauffer, Saashi A. Bedford

et al.

Molecular Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Abstract Genetic variants linked to autism are thought change cognition and behaviour by altering the structure function of brain. Although a substantial body literature has identified structural brain differences in autism, it is unknown whether autism-associated common genetic changes cortical macro- micro-structure. We investigated this using neuroimaging data from adults (UK Biobank, N = 31,748) children (ABCD, 4928). Using polygenic scores correlations we observe robust negative association between for magnetic resonance imaging derived phenotype neurite density (intracellular volume fraction) general population. This result consistent across both adults, cortex white matter tracts, confirmed correlations. There were no sex association. Mendelian randomisation analyses provide evidence causal relationship intracellular fraction, although should be revisited better powered instruments. Overall, study provides shared variant genetics density.

Language: Английский

Citations

1
Improving multi-trait genomic prediction by incorporating local genetic correlations DOI Creative Commons

Teng Jun,

Tingting Zhai, Xinyi Zhang

et al.

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

Published: Feb. 25, 2025

Genomic prediction holds significant potential for advancing precision medicine in humans, as well accelerating genetic improvement animals and plants. For multi-trait prediction, the conventional models are primarily based on global correlations between traits. With development of local correlation (LGC) estimation methods, it is now possible to analyze LGCs confined specific genomic regions expected that incorporating into model would enhance ability. Here, we proposed three address this issue evaluated their performances using simulated data real datasets from human, cow, pig populations. Our results demonstrate heterogeneous across genome increase accuracy by an average 12.76% ± 2.07% compared method (MTGBLUP) datasets. findings highlight importance considering improving prediction. Three methods incorporate could universally improve methods.

Language: Английский

Citations

1
Role of air pollution exposure in the alteration of brain cortical structure: A Mendelian randomization study DOI Creative Commons
Chaojuan Huang,

Zimei Cheng,

Xu Wu

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 297, P. 118221 - 118221

Published: April 29, 2025

Language: Английский

Citations

1
What is the neurobiology of schizophrenia? DOI Creative Commons
Michael A. Cummings,

Ai-Li W. Arias,

Stephen M. Stahl

et al.

CNS Spectrums, Journal Year: 2024, Volume and Issue: 30(1)

Published: Oct. 30, 2024

Abstract Schizophrenia spectrum disorders are brain diseases that developmental dementias (dementia praecox). Their pathology begins in utero with psychosis most commonly becoming evident adolescence and early adulthood. It is estimated they afflict the U.S. population at a prevalence rate of approximately 0.8%. Genetic studies indicate these about 80% determined by genes 20% environmental risk factors. Inheritance polygenic some 270 gene loci having been identified as contributing to for schizophrenia. Interestingly, many polymorphisms involved formation maturation. The genetic epigenetic risks give rise which neuroblasts migrate abnormally, assume abnormal locations orientations, vulnerable excessive neuronal synaptic loss, resulting overt psychotic illness. illness trajectory schizophrenia then one loss mass related number active exacerbations duration untreated In this context, molecules such dopamine, glutamate, serotonin play critical roles respect positive, negative, cognitive domains Acutely, antipsychotics ameliorate illness, especially positive signs symptoms. long-term effects antipsychotic medications have debated; however, bulk imaging data suggest slow but do not reverse Long-acting injectable (LAI) appear superior regard. Clozapine remains “gold standard” managing treatment-resistant

Language: Английский

Citations

5
The Contribution of Mosaic Chromosomal Alterations to Schizophrenia DOI
Kaihui Chang,

Xuemin Jian,

Chuanhong Wu

et al.

Biological Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Language: Английский

Citations

3
Synchronization stability of epileptic brain network with higher-order interactions DOI
Zhaohui Li, Chenlong Wang,

Mindi Li

et al.

Chaos An Interdisciplinary Journal of Nonlinear Science, Journal Year: 2025, Volume and Issue: 35(1)

Published: Jan. 1, 2025

Generally, epilepsy is considered as abnormally enhanced neuronal excitability and synchronization. So far, previous studies on the synchronization of epileptic brain networks mainly focused strength, but stability has not yet been explored deserved. In this paper, we propose a novel idea to construct hypergraph network (HGBN) based phase Furthermore, apply framework nonlinear coupled oscillation dynamic model (generalized Kuramoto model) investigate HGBNs patients. Specifically, quantified by calculating eigenvalue spectrum higher-order Laplacian matrix in HGBN. Results show that decreased slightly early stages seizure increased significantly prior termination. This indicates an emergency self-regulation mechanism may facilitate termination seizures. Moreover, variation during seizures be induced topological changes epileptogenic zones (EZs) Finally, verify interactions improve study proves validity with dynamical HGBN, emphasizing importance influence EZs

Language: Английский

Citations

0
Genome-wide analysis identifies novel shared loci between depression and white matter microstructure DOI Creative Commons

Qiyu Zhao,

Shuo Wang, Di Xiong

et al.

Molecular Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Depression, a complex and heritable psychiatric disorder, is associated with alterations in white matter microstructure, yet their shared genetic basis remains largely unclear. Utilizing the largest available genome-wide association study (GWAS) datasets for depression (N = 674,452) microstructure 33,224), assessed through diffusion tensor imaging metrics such as fractional anisotropy (FA) mean diffusivity (MD), we employed linkage disequilibrium score regression method to estimate global correlations, local analysis of [co]variant approach pinpoint genomic regions conjunctional false discovery rate identify variants. Our findings revealed that showed significant correlations FA 37 MD 59 regions, while were weak. Variant-level identified 78 distinct loci jointly (25 novel loci) (35 loci), 41 (17 loci). Further analyses these exhibited both concordant discordant effect directions between traits, well overlapping hemispheric patterns architecture. Enrichment implicated biological processes related metabolism regulation. This provides evidence mixed-direction architecture microstructure. The identification specific pathways offers potential insights developing targeted interventions improve integrity alleviate depressive symptoms.

Language: Английский

Citations

0
Cortical differences across psychiatric disorders and associated common and rare genetic variants DOI Creative Commons
Kuldeep Kumar, Zhijie Liao, Jakub Kopál

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 19, 2025

Genetic studies have identified common and rare variants increasing the risk for neurodevelopmental psychiatric disorders (NPDs). These also been shown to influence structure of cerebral cortex. However, it is unknown whether cortical differences associated with genetic are linked they confer NPDs. To answer this question, we analyzed thickness (CT) surface area (SA) NPDs, in ∼33000 individuals from general population clinical cohorts, as well ENIGMA summary statistics 8 Rare NPDs were preferentially total SA, while mean CT. Larger effects on CT, but not observed NPD medicated subgroups. At regional level, sensorimotor areas, showed higher association areas. We show that schizophrenia- bipolar-disorder- SNPs positive negative effect sizes SA suggesting their aggregated cancel out additive polygenic models. Overall, CT do relate those across individual may be critical non-genetic factors, such medication lived experience disorder.

Language: Английский

Citations

0