Opportunities and challenges of single-cell and spatially resolved genomics methods for neuroscience discovery

Nature Neuroscience, Год журнала: 2024, Номер 27(12), С. 2292 - 2309

Опубликована: Дек. 1, 2024

Язык: Английский

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Effects of gene dosage and development on subcortical nuclei volumes in individuals with 22q11.2 copy number variations

Neuropsychopharmacology, Год журнала: 2024, Номер 49(6), С. 1024 - 1032

Опубликована: Март 2, 2024

Abstract The 22q11.2 locus contains genes critical for brain development. Reciprocal Copy Number Variations (CNVs) at this impact risk neurodevelopmental and psychiatric disorders. Both deletions (22qDel) duplications (22qDup) are associated with autism, but 22qDel uniquely elevates schizophrenia risk. Understanding phenotypes these highly penetrant CNVs can provide insights into genetic pathways underlying neuropsychiatric Human neuroimaging animal models indicate subcortical alterations in 22qDel, yet little is known about developmental differences across specific nuclei between reciprocal CNV carriers typically developing (TD) controls. We conducted a longitudinal MRI study total of 385 scans from ( n = 96, 191, 53.1% female), 22qDup 37, 64, 45.9% TD controls 80, 130, 51.2% wide age range (5.5–49.5 years). Volumes the thalamus, hippocampus, amygdala, anatomical subregions were estimated using FreeSurfer, linear effects gene dosage non-linear characterized generalized additive mixed (GAMMs). Positive (volume increasing copy number) observed intracranial whole hippocampus volumes, not thalamus or amygdala volumes. Several exhibited similar positive effects, bi-directional found thalamic nuclei. Distinct age-related trajectories three groups. Notably, both flattened development hippocampal CA2/3 subfields relative to This provides novel on structures their trajectories.

Язык: Английский

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The pleiotropic spectrum of proximal 16p11.2 CNVs

The American Journal of Human Genetics, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

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Highly demarcated structural alterations in the brain and impaired social incentive learning in Tbx1 heterozygous mice

Molecular Psychiatry, Год журнала: 2024, Номер unknown

Опубликована: Окт. 27, 2024

Copy number variants (CNVs) are robustly associated with psychiatric disorders and changes in brain structures. However, because CNVs contain many genes, the precise gene-phenotype relationship remains unclear. Although various volumetric alterations brains of 22q11.2 CNV carriers have been identified humans mouse models, it is unknown how each gene encoded region contributes to structural alterations, mental illnesses, their dimensions. Our previous studies Tbx1, a T-box family transcription factor CNV, as driver for social interaction communication, spatial working memory, cognitive flexibility. unclear TBX1 impacts volumes regions functionally linked behavioral In this study, we used magnetic resonance imaging analysis comprehensively evaluate relevant affected structures congenic Tbx1 heterozygous mice. data showed that anterior posterior portions amygdaloid complex its surrounding cortical were most reduced an amygdala-dependent task, mice impaired ability learn incentive value partner. The primary secondary auditory cortexes increased, acoustic, but not non-acoustic, sensorimotor gating was findings identify brain's regional volume dimensions heterozygosity.

Язык: Английский

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Genomics of Attention Deficit Hyperactivity Disorder

Psychiatric Clinics of North America, Год журнала: 2025, Номер 48(2), С. 361 - 376

Опубликована: Фев. 28, 2025

Язык: Английский

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Cortical differences across psychiatric disorders and associated common and rare genetic variants

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

Опубликована: Апрель 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.

Язык: Английский

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Large-Scale Neuroimaging of Mental Illness

Current topics in behavioral neurosciences, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Язык: Английский

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Population Neuroscience: Principles and Advances

Current topics in behavioral neurosciences, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Язык: Английский

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Subcortical Anatomy in Neurogenetic Disorders: New Findings and Future Questions

American Journal of Psychiatry, Год журнала: 2023, Номер 180(9), С. 634 - 635

Опубликована: Сен. 1, 2023

Язык: Английский

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Effects of Gene Dosage and Development on Subcortical Nuclei Volumes in Individuals with 22q11.2 Copy Number Variations

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 1, 2023

The 22q11.2 locus contains genes critical for brain development. Reciprocal Copy Number Variations (CNVs) at this impact risk neurodevelopmental and psychiatric disorders. Both deletions (22qDel) duplications (22qDup) are associated with autism, but 22qDel uniquely elevates schizophrenia risk. Understanding phenotypes these highly penetrant CNVs can provide insights into genetic pathways underlying neuropsychiatric Human neuroimaging animal models indicate subcortical alterations in 22qDel, yet little is known about developmental differences across specific nuclei between reciprocal CNV carriers typically developing (TD) controls. We conducted a longitudinal MRI study (n=96, 53.1% female), 22qDup (n=37, 45.9% TD controls (n=80, 51.2% wide age range (5.5-49.5 years). Volumes of the thalamus, hippocampus, amygdala, anatomical subregions were estimated using FreeSurfer, effect gene dosage was examined linear mixed models. Age-related changes characterized general additive (GAMMs). Positive effects (22qDel < 22qDup) observed total intracranial whole hippocampus volumes, not thalamus or amygdala volumes. Several exhibited similar positive effects, bi-directional found thalamic nuclei. Distinct age-related trajectories three groups. Notably, both flattened development hippocampal CA2/3 subfields relative to This provides novel on structures their trajectories.

Язык: Английский

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