The Landscape of Shared and Divergent Genetic Influences across 14 Psychiatric Disorders

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

Опубликована: Янв. 15, 2025

Abstract Psychiatric disorders display high levels of comorbidity and genetic overlap 1,2 . Genomic methods have shown that even for schizophrenia bipolar disorder, two long-thought to be etiologically distinct 3 , the majority signal is shared 4 Furthermore, recent cross-disorder analyses uncovered over a hundred pleiotropic loci across eight 5 However, full scope disorder-specific basis psychopathology remains largely uncharted. Here, we address this gap by triangulating suite cutting-edge statistical functional genomic applied 14 childhood- adult-onset psychiatric (1,056,201 cases). Our identify characterize five underlying factors 6 explain variance individual (∼66% on average) are associated with 268 loci. We observed particularly polygenic 7 local correlation 8 very few 9 defined by: ( i ) disorder (“SB factor”), ii major depression, PTSD, anxiety (“internalizing factor”). At level, multiple 10–12 which demonstrated SB factor was substantially enriched in genes expressed excitatory neurons, whereas internalizing oligodendrocyte biology. By comparison, all broad biological processes (e.g., transcriptional regulation). These results indicate increasing differentiation function at different risk, from quite general vulnerability more specific pathways subsets disorders. observations may inform neurobiologically valid nosology implicate novel targets therapeutic developments designed treat commonly occurring comorbid presentations.

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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Genomics of Anxiety Disorders

Psychiatric Clinics of North America, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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Psychiatric genetics in the diverse landscape of Latin American populations

Nature Genetics, Год журнала: 2025, Номер unknown

Опубликована: Апрель 2, 2025

Язык: Английский

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Exploring the implications of case selection methods for psychiatric molecular genetic studies

Molecular Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 20, 2025

Abstract Researchers selecting probands for molecular genetic studies confront a range of sampling issues with modest empirical guidance. In this paper, using cases major depression (MD), anxiety disorders (AD) alcohol use disorder (AUD), drug (DUD), bipolar (BD) and schizophrenia (SZ) from large population cohort all native Swedes born 1940–2003, we examine the implications three proband selection decisions by exploring profiles risks assessed validated family risk scores. The impact censoring comorbid diagnoses is quite variable, depending on frequency that in case sample relationship censored to primary disorder. an MD cohort, SZ produces only focal small decrease while AD wide-spread reduction most other disorders. We value SZ, BD whose onset was preceded one two years first episodes DUD or AUD. do not see any increase these “screened” cohorts. Secondary ascertainment, where A ascertained as diagnosis collected B, can, certain situations, increases B associated A. However, if closely genetically related (as seen MD/AD DUD/AUD pairings), pattern differs dramatically general moderate elevation across profile. These findings provide guidelines future investigators suggest caution when screening out utilizing secondary ascertainment.

Язык: Английский

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Comorbidity alters the genetic relationship between anxiety disorders and major depression

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

Опубликована: Ноя. 20, 2024

There is extensive comorbidity between anxiety disorders (ANX) and major depression (MD). Most studies on the genetics of ANX do not exclude comorbid cases MD,

Язык: Английский

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