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1.
Hum Brain Mapp ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33027543

RESUMO

First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.

2.
Nat Commun ; 11(1): 4637, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32934226

RESUMO

An association between schizophrenia and subsequent breast cancer has been suggested; however the risk of schizophrenia following a breast cancer is unknown. Moreover, the driving forces of the link are largely unclear. Here, we report the phenotypic and genetic positive associations of schizophrenia with breast cancer and vice versa, based on a Swedish population-based cohort and GWAS data from international consortia. We observe a genetic correlation of 0.14 (95% CI 0.09-0.19) and identify a shared locus at 19p13 (GATAD2A) associated with risks of breast cancer and schizophrenia. The epidemiological bidirectional association between breast cancer and schizophrenia may partly be explained by the genetic overlap between the two phenotypes and, hence, shared biological mechanisms.


Assuntos
Neoplasias da Mama/genética , Fatores de Transcrição GATA/genética , Esquizofrenia/genética , Idoso , Cromossomos Humanos Par 19/genética , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Suécia
4.
Nat Commun ; 11(1): 1842, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32296054

RESUMO

Despite considerable progress in schizophrenia genetics, most findings have been for large rare structural variants and common variants in well-imputed regions with few genes implicated from exome sequencing. Whole genome sequencing (WGS) can potentially provide a more complete enumeration of etiological genetic variation apart from the exome and regions of high linkage disequilibrium. We analyze high-coverage WGS data from 1162 Swedish schizophrenia cases and 936 ancestry-matched population controls. Our main objective is to evaluate the contribution to schizophrenia etiology from a variety of genetic variants accessible to WGS but not by previous technologies. Our results suggest that ultra-rare structural variants that affect the boundaries of topologically associated domains (TADs) increase risk for schizophrenia. Alterations in TAD boundaries may lead to dysregulation of gene expression. Future mechanistic studies will be needed to determine the precise functional effects of these variants on biology.


Assuntos
Estudo de Associação Genômica Ampla/métodos , Esquizofrenia/genética , Encéfalo/metabolismo , Exoma/genética , Genoma Humano/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Sistema Nervoso/metabolismo , Controle de Qualidade , Análise de Sequência de DNA
5.
Biol Psychiatry ; 87(12): 1045-1051, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32199606

RESUMO

BACKGROUND: While genetic variation has a known impact on the risk for obsessive-compulsive disorder (OCD), there is also evidence that there are maternal components to this risk. Here, we partitioned sources of variation, including direct genetic and maternal effects, on risk for OCD. METHODS: The study population consisted of 822,843 individuals from the Swedish Medical Birth Register, born in Sweden between January 1, 1982, and December 31, 1990, and followed for a diagnosis of OCD through December 31, 2013. Diagnostic information about OCD was obtained using the Swedish National Patient Register. RESULTS: A total of 7184 individuals in the birth cohort (0.87%) were diagnosed with OCD. After exploring various generalized linear mixed models to fit the diagnostic data, genetic maternal effects accounted for 7.6% (95% credible interval: 6.9%-8.3%) of the total variance in risk for OCD for the best model, and direct additive genetics accounted for 35% (95% credible interval: 32.3%-36.9%). These findings were robust under alternative models. CONCLUSIONS: Our results establish genetic maternal effects as influencing risk for OCD in offspring. We also show that additive genetic effects in OCD are overestimated when maternal effects are not modeled.

6.
Soc Psychiatry Psychiatr Epidemiol ; 55(10): 1383-1393, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31907560

RESUMO

PURPOSE: The EGOS study (Epidemiology and Genetics of Obsessive-compulsive disorder and chronic tic disorders in Sweden) is a large-scale, epidemiological, prospective cohort that is used to identify genetic and environmental risk factors in the etiology of obsessive-compulsive disorder (OCD) and chronic tic disorders (CTD). METHODS: Individuals born between January 1954 and December 1998 with at least two diagnoses of OCD or CTD at different timepoints in the National Patient Register (NPR), and followed between January 1997 and December 2012, represent the EGOS source population (n = 20,374). The Swedish Multi-Generation Registry (MGR) are then used to define family relatedness for all cases and additional phenotypic and demographic data added to the resultant database. To create an epidemiologically valid subset of the source cohort that also includes biospecimens and additional phenotyping, we contact cases from within the source population. To date, 6832 invitations have been sent out and 1853 (27%) have elected to participate in the EGOS biospecimen collection. RESULTS: To date, 1608 biological samples have been collected, of which 1249 are genotyped and 832 supplementary Obsessive-Compulsive Inventory-Revised (OCI-R) and/or Florida Obsessive-Compulsive Inventory (FOCI) have been completed by individuals with OCD and/or CTD, age 16-64 years. DNA samples are genotyped using Infinium Global Screening Array and will undergo whole-exome sequencing in the future. Detailed information is available for each individual through linkage to the Swedish national registers, e.g., identification of additional psychiatric diagnoses, medical diagnoses, birth-related variables, and relevant demographic and social data. CONCLUSION: EGOS benefits from a genetically homogeneous sample with epidemiological ascertainment, minimizing the risk of confounding due to population stratification on ascertainment bias. In addition, this study is built upon clinical diagnoses of OCD and CTD in specialized psychiatric care, which reduces further biases and case misclassification.


Assuntos
Transtorno Obsessivo-Compulsivo , Transtornos de Tique , Síndrome de Tourette , Humanos , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno Obsessivo-Compulsivo/genética , Estudos Prospectivos , Suécia/epidemiologia , Transtornos de Tique/diagnóstico , Transtornos de Tique/epidemiologia , Transtornos de Tique/genética
7.
Biol Psychiatry ; 87(8): 736-744, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31767120

RESUMO

BACKGROUND: Genetic studies of schizophrenia have implicated numerous risk loci including several copy number variants (CNVs) of large effect and hundreds of loci of small effect. In only a few cases has a specific gene been clearly identified. Rare CNVs affecting a single gene offer a potential avenue to discovering schizophrenia risk genes. METHODS: CNVs were generated from exome sequencing of 4913 schizophrenia cases and 6188 control subjects from Sweden. We integrated two CNV calling methods (XHMM and ExomeDepth) to expand our set of single-gene CNVs and leveraged two different approaches for validating these variants (quantitative polymerase chain reaction and NanoString). RESULTS: We found a significant excess of all rare CNVs (deletions: p = .0004, duplications: p = .0006) and single-gene CNVs (deletions: p = .04, duplications: p = .03) in schizophrenia cases compared with control subjects. An expanded set of CNVs generated from integrating multiple approaches showed a significant burden of deletions in 11 of 21 gene sets previously implicated in schizophrenia and across all genes in those sets (p = .008), although no tests survived correction. We performed an extensive validation of all deletions in the significant set of voltage-gated calcium channels among CNVs called from both exome sequencing and genotyping arrays. In total, 4 exonic, single-gene deletions were validated in schizophrenia cases and none in control subjects (p = .039), of which all were identified by exome sequencing. CONCLUSIONS: These results point to the potential contribution of single-gene CNVs to schizophrenia, indicate that the utility of exome sequencing for CNV calling has yet to be maximized, and note that single-gene CNVs should be included in gene-focused studies using other classes of variation.

8.
Schizophr Bull ; 46(2): 319-327, 2020 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-31165892

RESUMO

Methylome-wide association studies (MWASs) are promising complements to sequence variation studies. We used existing sequencing-based methylation data, which assayed the majority of all 28 million CpGs in the human genome, to perform an MWAS for schizophrenia in blood, while controlling for cell-type heterogeneity with a recently generated platform-specific reference panel. Next, we compared the MWAS results with findings from 3 existing large-scale array-based schizophrenia methylation studies in blood that assayed up to ~450 000 CpGs. Our MWAS identified 22 highly significant loci (P < 5 × 10-8) and 852 suggestively significant loci (P < 1 × 10-5). The top finding (P = 5.62 × 10-11, q = 0.001) was located in MFN2, which encodes mitofusin-2 that regulates Ca2+ transfer from the endoplasmic reticulum to mitochondria in cooperation with DISC1. The second-most significant site (P = 1.38 × 10-9, q = 0.013) was located in ALDH1A2, which encodes an enzyme for astrocyte-derived retinoic acid-a key neuronal morphogen with relevance for schizophrenia. Although the most significant MWAS findings were not assayed on the arrays, we observed significant enrichment of overlapping findings with 2 of the 3 array datasets (P = 0.0315, 0.0045, 0.1946). Overrepresentation analysis of Gene Ontology terms for the genes in the significant overlaps suggested high similarity in the biological functions detected by the different datasets. Top terms were related to immune and/or stress responses, cell adhesion and motility, and a broad range of processes essential for neurodevelopment.

9.
Mol Psychiatry ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31712719

RESUMO

A high proportion of those with schizophrenia experience treatment non-response, placing them at higher risk for mortality and suicide attempts, compared to treatment responders. The clinical, social, and economic burden of treatment-resistant schizophrenia (TRS) are substantial. Previous genomic and epidemiological studies of TRS were often limited by sample size or lack of comprehensive genomic data. We aimed to systematically understand the clinical, demographic, and genomic correlates of TRS using epidemiological and genetic epidemiological modelling in a Swedish national population sample (n = 24,706) and then in a subgroup with common variant genetic risk scores, rare copy-number variant burden, and rare exonic burden (n = 4936). Population-based analyses identified increasing schizophrenia family history to be significantly associated with TRS (highest quartile of familial burden vs. lowest: adjusted odds ratio (aOR): 1.31, P = 4.8 × 10-8). In males, a decrease of premorbid IQ of one standard deviation was significantly associated with greater risk of TRS (minimal aOR: 0.94, P = 0.002). In a subset of cases with extensive genomic data, we found no significant association between the genetic risk scores of four psychiatric disorders and two cognitive traits with TRS (schizophrenia genetic risk score: aOR = 1.07, P = 0.067). The association between copy number variant and rare variant burden measures and TRS did not reach the pre-defined statistical significance threshold (all P ≥ 0.005). In conclusion, direct measures of genomic risk were not associated with TRS; however, premorbid IQ in males and schizophrenia family history were significantly correlated with TRS and points to new insights into the architecture of TRS.

10.
Transl Psychiatry ; 9(1): 192, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31431615

RESUMO

Our recent study has demonstrated that increased connectivity in the cerebello-thalamo-cortical (CTC) circuitry is a state-independent neural trait that can potentially predict the onset of psychosis. One possible cause of such "trait" abnormality would be genetic predisposition. Here, we tested this hypothesis using multi-paradigm functional magnetic resonance imaging (fMRI) data from two independent twin cohorts. In a sample of 85 monozygotic (MZ) and 52 dizygotic (DZ) healthy twin pairs acquired from the Human Connectome Project, we showed that the connectivity pattern of the identified CTC circuitry was more similar in the MZ twins (r = 0.54) compared with that in the DZ twins (r = 0.22). The structural equation modeling analysis revealed a heritability estimate of 0.52 for the CTC connectivity, suggesting a moderately strong genetic effect. Moreover, using an independent schizophrenia cotwin sample (10 discordant MZ cotwins, 30 discordant DZ cotwins, and 32 control cotwins), we observed a significant linear relationship between genetic distance to schizophrenia and the connectivity strength in the CTC circuitry (i.e., schizophrenia MZ cotwins > schizophrenia DZ cotwins > control twins, P = 0.045). The present data provide converging evidence that increased connectivity in the CTC circuitry is likely to be a heritable trait that is associated with the genetic risk of schizophrenia.


Assuntos
Encéfalo/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Doenças em Gêmeos/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Adulto , Conectoma , Doenças em Gêmeos/genética , Feminino , Predisposição Genética para Doença , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Esquizofrenia/genética
11.
Biol Psychiatry ; 86(7): 545-556, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31443932

RESUMO

BACKGROUND: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects. METHODS: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects. RESULTS: FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects. CONCLUSIONS: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31302732

RESUMO

Preclinical studies indicate a link between the kynurenine pathway and monocyte chemoattractant protein-1 (MCP-1), but there is a lack of clinical studies examining this further. We here perform a secondary analysis of kynurenine metabolites and MCP-1 in cerebrospinal fluid of 23 twins affected from schizophrenia, bipolar disorder or unaffected. We show an association between MCP-1 and kynurenic acid (KYNA), driven by unique environmental influences and a less pronounced association between MCP-1 and tryptophan. No association was detected between MCP-1 and quinolinic acid. Further studies on the mechanism behind the putative relationship between KYNA and MCP-1 are needed.

13.
Psychiatry Res ; 278: 180-187, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31207455

RESUMO

Twin- and family studies have shown variations in the heritability estimates of bipolar disorder (BPD). The current study uses an updated statistical methodology for heritability estimation in BPD by taking available time of follow-up into account while controlling for co-variates. We identified monozygotic and dizygotic same and different sex twins with BPD (n = 804) or unaffected from BPD (n = 91,604) from the Swedish Twin Register and the National Patient Register. We applied structural equational modeling with inversed probability weighting to estimate the heritability, taking into account censoring and truncation of data. Sex-limitation models were constructed to analyze qualitative or quantitative sex-differences in BPD. Heritability for BPD was 60.4% (95% Confidence Interval: 50.3-70.5) after age, sex, left-hand truncation and censoring of the data was taken into account. A larger proportion of females were affected from BPD (females 62.2%; males 37.8%, p < 0.001), but no sex-difference in BPD heritability was found, nor any sex-specific genetic effects. We demonstrated a robust 60% heritability for BPD with no evidence of sex-specific genetic effects on disease liability.


Assuntos
Transtorno Bipolar/epidemiologia , Transtorno Bipolar/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Sistema de Registros , Caracteres Sexuais , Adulto , Doenças em Gêmeos/genética , Feminino , Humanos , Masculino , Suécia
14.
Cancer Epidemiol Biomarkers Prev ; 28(7): 1252-1258, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31040135

RESUMO

BACKGROUND: Genome-wide association studies have identified germline genetic variants in 25 genetic loci that increase the risk of developing glioma in adulthood. It is not known if these variants increase the risk of developing glioma in children and adolescents and young adults (AYA). To date, no studies have performed genome-wide analyses to find novel genetic variants associated with glioma risk in children and AYA. METHODS: We investigated the association between 8,831,628 genetic variants and risk of glioma in 854 patients diagnosed up to the age of 29 years and 3,689 controls from Sweden and Denmark. Recruitment of patients and controls was population based. Genotyping was performed using Illumina BeadChips, and untyped variants were imputed with IMPUTE2. We selected 41 established adult glioma risk variants for detailed investigation. RESULTS: Three adult glioma risk variants, rs634537, rs2157719, and rs145929329, all mapping to the 9p21.3 (CDKN2B-AS1) locus, were associated with glioma risk in children and AYA. The strongest association was seen for rs634537 (odds ratioG = 1.21; 95% confidence interval = 1.09-1.35; P = 5.8 × 10-4). In genome-wide analysis, an association with risk was suggested for 129 genetic variants (P <1 × 10-5). CONCLUSIONS: Carriers of risk alleles in the 9p21.3 locus have an increased risk of glioma throughout life. The results from genome-wide association analyses require validation in independent cohorts. IMPACT: Our findings line up with existing evidence that some, although not all, established adult glioma risk variants are associated with risk of glioma in children and AYA. Validation of results from genome-wide analyses may reveal novel susceptibility loci for glioma in children and AYA.

15.
Nat Genet ; 51(3): 431-444, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30804558

RESUMO

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.


Assuntos
Transtorno do Espectro Autista/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Dinamarca , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Herança Multifatorial/genética , Fenótipo , Fatores de Risco
16.
Biol Psychiatry ; 86(2): 110-119, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-30686506

RESUMO

BACKGROUND: Genetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. Subtypes of BD including schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I), and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania, and depression. The genetic factors contributing to the combination of symptoms among these subtypes are poorly understood. METHODS: Rare large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis, and 307 with unknown psychosis history], 1436 BD II, 579 SAB, and 505 BD not otherwise specified) and 8656 controls. CNV burden and a polygenic risk score (PRS) for schizophrenia were used to evaluate the relative contributions of rare and common variants to risk of BD, BD subtypes, and psychosis. RESULTS: CNV burden did not differ between BD and controls when treated as a single diagnostic entity. However, burden in SAB was increased relative to controls (p = .001), BD I (p = .0003), and BD II (p = .0007). Burden and schizophrenia PRSs were increased in SAB compared with BD I with psychosis (CNV p = .0007, PRS p = .004), and BD I without psychosis (CNV p = .0004, PRS p = 3.9 × 10-5). Within BD I, psychosis was associated with increased schizophrenia PRSs (p = .005) but not CNV burden. CONCLUSIONS: CNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.

17.
Scand J Public Health ; 47(2): 260-268, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29708026

RESUMO

AIMS: Following the 2004 Southeast Asian tsunami, Swedish authorities received public criticism for slow implementation of rescue work. Meanwhile, data are scarce on survivors' perspectives and potential mental health symptoms associated with timing of evacuation. Therefore, the aim of this study was to investigate survivors' contentment with evacuation time and whether duration at disaster site following the 2004 tsunami was associated with post-traumatic stress symptoms (PTSS) and psychological morbidity. METHODS: Of 10,116 Swedish tsunami survivors who returned to Sweden in the first 3 weeks post tsunami, 4910 (49%) answered a questionnaire 14 months later including questions on evacuation time, contentment with evacuation time and PTSS (Impact of Event Scale). We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CI) of PTSS by timing of evacuation adjusting for gender, age, education, various indicators of trauma exposure and pre-tsunami psychiatric diagnoses. RESULTS: More than half of the survivors (53%) were content with evacuation time while 33% wanted later evacuation and 13% earlier evacuation. Compared with those evacuated 14-21 days post tsunami, individuals evacuated at day 1-4 presented with increased odds of PTSS (crude OR 3.0, 95% CI 2.0-4.5; and multivariable adjusted OR 2.0, 95% CI 1.3-3.0) and impaired mental health (crude OR 1.7, 95% CI 1.2-2.4; and multivariable adjusted OR 1.4 95% CI 1.0-2.0). CONCLUSIONS: One-third of Swedish tsunami survivors preferred a later evacuation from disaster sites. These findings call for further studies, with prospective designs, to disentangle the causal direction of the association between evacuation time and PTSS.


Assuntos
Desastres , Trabalho de Resgate/organização & administração , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Sobreviventes/psicologia , Tsunamis , Adolescente , Adulto , Ásia Sudeste/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Sobreviventes/estatística & dados numéricos , Suécia/epidemiologia , Adulto Jovem
18.
Schizophr Res ; 204: 183-192, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30121189

RESUMO

The schizophrenia and bipolar twin study in Sweden (STAR) is a large nation-wide cohort of monozygotic (MZ) and dizygotic (DZ) same-sex twins with schizophrenia or bipolar disorder and healthy control pairs, extensively characterized with brain imaging, neuropsychological tests, biomarkers, genetic testing, psychiatric symptoms and personality traits. The purpose is to investigate genetic and environmental mechanisms that give rise to schizophrenia and bipolar disorder as well as the intermediate phenotypes. This article describes the design, recruitment, data collection, measures, collected twins' characteristics, diagnostic procedures as well as ongoing and planned analyses. Identification of biomarkers, genetic and epigenetic variation and the development of specific and common endophenotypes for schizophrenia and bipolar disorder are potential gains from this cohort.


Assuntos
Transtorno Bipolar , Endofenótipos , Interação Gene-Ambiente , Sistema de Registros , Esquizofrenia , Adulto , Idoso , Biomarcadores , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/etiologia , Transtorno Bipolar/genética , Transtorno Bipolar/fisiopatologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/etiologia , Esquizofrenia/genética , Esquizofrenia/fisiopatologia , Suécia , Adulto Jovem
19.
Clin Epidemiol ; 10: 1817-1826, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555264

RESUMO

Background: The consequences of autism in pregnancy outcomes have not been explored before, although it is of crucial importance because of the frequent comorbidities and medication in this group of women. Objectives: To estimate the risk of adverse pregnancy outcomes in women diagnosed with autism. Design: Nationwide population-based cohort study. Setting: Sweden. Participants: Singleton births identified in the Swedish Medical Birth Registry, 2006-2014. A total of 2,198 births to women diagnosed with autism registered in the Swedish National Patient Registry were compared to 877,742 singleton births to women without such a diagnosis. Main outcome and measures: Preterm delivery. Secondary measures were cesarean delivery (emergency and elective), Apgar score <7 at 5 minutes, small for gestational age, large for gestational age, stillbirth, gestational diabetes, and preeclampsia. ORs were calculated through logistic regression, adjusted for maternal age at delivery, maternal country of birth, smoking, maternal body mass index, parity, calendar year of birth, and psychotropic and antiepileptic medication during pregnancy. Results: Women with autism were at increased risk of preterm birth (OR=1.30; 95% CI=1.10-1.54), especially medically indicated preterm birth (OR=1.41; 95% CI=1.08-1.82), but not with spontaneous preterm birth. Maternal autism was also associated with an increased risk of elective cesarean delivery (OR=1.44; 95% CI=1.25-1.66) and preeclampsia (OR=1.34; 95% CI=1.08-1.66), but not with emergency cesarean delivery, low Apgar score (<7), large for gestational age, gestational diabetes, and stillbirth. In women with medication during pregnancy, there was no increased risk of adverse pregnancy outcome except for induction of delivery (OR=1.33; 95% CI=1.14-1.55). Conclusion and relevance: Maternal autism is associated with preterm birth, likely due to an increased frequency of medically indicated preterm births, but also with other adverse pregnancy outcomes, suggesting a need for extra surveillance during prenatal care.

20.
Transl Psychiatry ; 8(1): 210, 2018 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-30297702

RESUMO

Ankyrin-3 (ANK3) is one of the few genes that have been consistently identified as associated with bipolar disorder by multiple genome-wide association studies. However, the exact molecular basis of the association remains unknown. A rare loss-of-function splice-site SNP (rs41283526*G) in a minor isoform of ANK3 (incorporating exon ENSE00001786716) was recently identified as protective of bipolar disorder and schizophrenia. This suggests that an elevated expression of this isoform may be involved in the etiology of the disorders. In this study, we used novel approaches and data sets to test this hypothesis. First, we strengthen the statistical evidence supporting the allelic association by replicating the protective effect of the minor allele of rs41283526 in three additional large independent samples (meta-analysis p-values: 6.8E-05 for bipolar disorder and 8.2E-04 for schizophrenia). Second, we confirm the hypothesis that both bipolar and schizophrenia patients have a significantly higher expression of this isoform than controls (p-values: 3.3E-05 for schizophrenia and 9.8E-04 for bipolar type I). Third, we determine the transcription start site for this minor isoform by Pacific Biosciences sequencing of full-length cDNA and show that it is primarily expressed in the corpus callosum. Finally, we combine genotype and expression data from a large Norwegian sample of psychiatric patients and controls, and show that the risk alleles in ANK3 identified by bipolar disorder GWAS are located near the transcription start site of this isoform and are significantly associated with its elevated expression. Together, these results point to the likely molecular mechanism underlying ANK3´s association with bipolar disorder.


Assuntos
Anquirinas/metabolismo , Transtorno Bipolar/genética , Transtorno Bipolar/metabolismo , Encéfalo/metabolismo , Predisposição Genética para Doença , Alelos , Estudos de Coortes , Regulação da Expressão Gênica no Desenvolvimento , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único , Isoformas de Proteínas/metabolismo , Fatores de Risco , Esquizofrenia/genética , Esquizofrenia/metabolismo
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