Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The conserved ASTN2/BRINP1 locus at 9q33.1-33.2 is associated with major psychiatric disorders in a large pedigree from Southern Spain.

ABSTRACT: We investigated the genetic causes of major mental disorders (MMDs) including schizophrenia, bipolar disorder I, major depressive disorder and attention deficit hyperactive disorder, in a large family pedigree from Alpujarras, South of Spain, a region with high prevalence of psychotic disorders. We applied a systematic genomic approach based on karyotyping (n = 4), genotyping by genome-wide SNP array (n = 34) and whole-genome sequencing (n = 12). We performed genome-wide linkage analysis, family-based association analysis and polygenic risk score estimates. Significant linkage was obtained at chromosome 9 (9q33.1-33.2, LOD score = 4.11), a suggestive region that contains five candidate genes ASTN2, BRINP1, C5, TLR4 and TRIM32, previously associated with MMDs. Comprehensive analysis associated the MMD phenotype with genes of the immune system with dual brain functions. Moreover, the psychotic phenotype was enriched for genes involved in synapsis. These results should be considered once studying the genetics of psychiatric disorders in other families, especially the ones from the same region, since founder effects may be related to the high prevalence.

SUBMITTER: Pol-Fuster J

PROVIDER: S-EPMC8282839 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

The genomics of major psychiatric disorders in a large pedigree from Northern Sweden.

Project description:We searched for genetic causes of major psychiatric disorders (bipolar disorder, schizoaffective disorder, and schizophrenia) in a large, densely affected pedigree from Northern Sweden that originated with three pairs of founders born around 1650. We applied a systematic genomic approach to the pedigree via karyotyping (N?=?9), genome-wide SNP arrays (N?=?418), whole-exome sequencing (N?=?26), and whole-genome sequencing (N?=?10). Comprehensive analysis did not identify plausible variants of strong effect. Rather, pedigree cases had significantly higher genetic risk scores compared to pedigree and community controls.

| S-EPMC6362018 | biostudies-literature

Analysis of human neuronal cells carrying ASTN2 deletion: A cross-disorder risk variant of psychiatric disorders

Project description:Recent genetic studies have found common genomic risk variants among psychiatric disorders, strongly suggesting the overlaps in their molecular and cellular mechanism. Our research group identified the variant in ASTN2 as one of the candidate risk factors across these psychiatric disorders by whole-genome copy number variation analysis. However, the alterations in the human neuronal cells resulting from ASTN2 variants identified in patients remain unknown. To address this, we used patient-derived and genome-edited iPS cells with ASTN2 deletion; cells were further differentiated into neuronal cells. A comprehensive gene expression analysis using genome-edited iPSC cells with the loss of function variants on both alleles revealed that the expression level of ZNF558, a gene specifically expressed in human forebrain neural progenitor cells, was greatly reduced in ASTN2-deleted neuronal cells.

2024-03-07 | GSE260713 | GEO

Large Scale Genotyping of Psychiatric Disorders

Project description:Large Scale Genotyping of Psychiatric Disorders

| PRJNA394934 | ENA

Genetic Variation in the ASTN2 Locus in Cardiovascular, Metabolic and Psychiatric Traits: Evidence for Pleiotropy Rather Than Shared Biology.

Project description:BackgroundThe link between cardiometabolic and psychiatric illness has long been attributed to human behaviour, however recent research highlights shared biological mechanisms. The ASTN2 locus has been previously implicated in psychiatric and cardiometabolic traits, therefore this study aimed to systematically investigate the genetic architecture of ASTN2 in relation to a wide range of relevant traits.MethodsBaseline questionnaire, assessment and genetic data of 402111 unrelated white British ancestry individuals from the UK Biobank was analysed. Genetic association analyses were conducted using PLINK 1.07, assuming an additive genetic model and adjusting for age, sex, genotyping chip, and population structure. Conditional analyses and linkage disequilibrium assessment were used to determine whether cardiometabolic and psychiatric signals were independent.ResultsAssociations between genetic variants in the ASTN2 locus and blood pressure, total and central obesity, neuroticism, anhedonia and mood instability were identified. All analyses support the independence of the cardiometabolic traits from the psychiatric traits. In silico analyses provide support for the central obesity signal acting through ASTN2, however most of the other signals are likely acting through other genes in the locus.ConclusionsOur systematic analysis demonstrates that ASTN2 has pleiotropic effects on cardiometabolic and psychiatric traits, rather than contributing to shared pathology.

| S-EPMC8391428 | biostudies-literature

Genetic risk scores for major psychiatric disorders and the risk of postpartum psychiatric disorders.

Project description:Postpartum psychiatric disorders are heritable, but how genetic liability varies by other significant risk factors is unknown. We aimed to (1) estimate associations of genetic risk scores (GRS) for major depression (MD), bipolar disorder (BD), and schizophrenia (SCZ) with postpartum psychiatric disorders, (2) examine differences by prior psychiatric history, and (3) compare genetic and familial risk of postpartum psychiatric disorders. We conducted a nested case-control study based on Danish population-based registers of all women in the iPSYCH2012 cohort who had given birth before December 31, 2015 (n = 8850). Cases were women with a diagnosed psychiatric disorder or a filled psychotropic prescription within one year after delivery (n = 5829 cases, 3021 controls). Association analyses were conducted between GRS calculated from Psychiatric Genomics Consortium discovery meta-analyses for MD, BD, and SCZ and case-control status of a postpartum psychiatric disorder. Parental psychiatric history was associated with postpartum psychiatric disorders among women with previous psychiatric history (OR, 1.14; 95% CI 1.02-1.28) but not without psychiatric history (OR, 1.08; 95% CI: 0.81-1.43). GRS for MD was associated with an increased risk of postpartum psychiatric disorders in both women with (OR, 1.44; 95% CI: 1.19-1.74) and without (OR, 1.88; 95% CI: 1.26-2.81) personal psychiatric history. SCZ GRS was only minimally associated with postpartum disorders and BD GRS was not. Results suggest GRS of lifetime psychiatric illness can be applied to the postpartum period, which may provide clues about distinct environmental or genetic elements of postpartum psychiatric disorders and ultimately help identify vulnerable groups.

| S-EPMC6848186 | biostudies-literature

Leveraging genetic overlap between irritability and psychiatric disorders to identify genetic variants of major psychiatric disorders.

Project description:Irritability is a heritable core mental trait associated with several psychiatric illnesses. However, the genomic basis of irritability is unclear. Therefore, this study aimed to 1) identify the genetic variants associated with irritability and investigate the associated biological pathways, genes, and tissues as well as single-nucleotide polymorphism (SNP)-based heritability; 2) explore the relationships between irritability and various traits, including psychiatric disorders; and 3) identify additional and shared genetic variants for irritability and psychiatric disorders. We conducted a genome-wide association study (GWAS) using 379,506 European samples (105,975 cases and 273,531 controls) from the UK Biobank. We utilized various post-GWAS analyses, including linkage disequilibrium score regression, the bivariate causal mixture model (MiXeR), and conditional and conjunctional false discovery rate approaches. This GWAS identified 15 independent loci associated with irritability; the total SNP heritability estimate was 4.19%. Genetic correlations with psychiatric disorders were most pronounced for major depressive disorder (MDD) and bipolar II disorder (BD II). MiXeR analysis revealed polygenic overlap with schizophrenia (SCZ), bipolar I disorder (BD I), and MDD. Conditional false discovery rate analyses identified additional loci associated with SCZ (number [n] of additional SNPs = 105), BD I (n = 54), MDD (n = 107), and irritability (n = 157). Conjunctional false discovery rate analyses identified 85, 41, and 198 shared loci between irritability and SCZ, BD I, and MDD, respectively. Multiple genetic loci were associated with irritability and three main psychiatric disorders. Given that irritability is a cross-disorder trait, these findings may help to elucidate the genomics of psychiatric disorders.

| S-EPMC10317967 | biostudies-literature

A polygenic p factor for major psychiatric disorders.

Project description:It has recently been proposed that a single dimension, called the p factor, can capture a person's liability to mental disorder. Relevant to the p hypothesis, recent genetic research has found surprisingly high genetic correlations between pairs of psychiatric disorders. Here, for the first time, we compare genetic correlations from different methods and examine their support for a genetic p factor. We tested the hypothesis of a genetic p factor by applying principal component analysis to matrices of genetic correlations between major psychiatric disorders estimated by three methods-family study, genome-wide complex trait analysis, and linkage-disequilibrium score regression-and on a matrix of polygenic score correlations constructed for each individual in a UK-representative sample of 7 026 unrelated individuals. All disorders loaded positively on a first unrotated principal component, which accounted for 57, 43, 35, and 22% of the variance respectively for the four methods. Our results showed that all four methods provided strong support for a genetic p factor that represents the pinnacle of the hierarchical genetic architecture of psychopathology.

| S-EPMC6168558 | biostudies-literature

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder.

Project description:Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n?~?260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.

| S-EPMC6175827 | biostudies-literature

Identification of Common Thalamocortical Dysconnectivity in Four Major Psychiatric Disorders.

Project description:BACKGROUND:Recent genetic and imaging analyses of large datasets suggested that common biological substrates exist across psychiatric diagnoses. Functional connectivity (FC) abnormalities of thalamocortical circuits were consistently found in patients with schizophrenia but have been less studied in other major psychiatric disorders. This study aimed to examine thalamocortical FC in 4 major psychiatric disorders to identify the common connectivity abnormalities across major psychiatric disorders. METHODS:This study recruited 100 patients with schizophrenia, 100 patients with bipolar I disorder, 88 patients with bipolar II disorder, 100 patients with major depressive disorder, and 160 healthy controls (HCs). Each participant underwent resting functional magnetic resonance imaging. The thalamus was used to derive FC maps, and group comparisons were made between each patient group and HCs using an independent-sample t test. Conjunction analysis was used to identify the common thalamocortical abnormalities among these 4 psychiatric disorders. RESULTS:The 4 groups of patients shared a similar pattern of thalamocortical dysconnectivity characterized by a decrease in thalamocortical FC with the dorsal anterior cingulate, anterior prefrontal cortex and inferior parietal cortex. The groups also showed an increase in FC with the postcentral gyrus, precentral gyrus, superior temporal cortex, and lateral occipital areas. Further network analysis demonstrated that the frontoparietal regions showing hypoconnectivity belonged to the salience network. CONCLUSION:Our findings provide FC evidence that supports the common network hypothesis by identifying common thalamocortical dysconnectivities across 4 major psychiatric disorders. The network analysis also supports the cardinal role of salience network abnormalities in major psychiatric disorders.

| S-EPMC6737486 | biostudies-literature

Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap.

Project description:The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how genetic variants impart brain dysfunction or pathology. We used transcriptomic profiling as a quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders-autism, schizophrenia, bipolar disorder, depression, and alcoholism-compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions. The degree of sharing of transcriptional dysregulation is related to polygenic (single-nucleotide polymorphism-based) overlap across disorders, suggesting a substantial causal genetic component. This comprehensive systems-level view of the neurobiological architecture of major neuropsychiatric illness demonstrates pathways of molecular convergence and specificity.

| S-EPMC5898828 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data