RESUMO
The major anxiety disorders (ANX; including generalized anxiety disorder, panic disorder, and phobias) are highly prevalent, often onset early, persist throughout life, and cause substantial global disability. Although distinct in their clinical presentations, they likely represent differential expressions of a dysregulated threat-response system. Here we present a genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases and 729,881 controls. We identified 58 independent genome-wide significant ANX risk variants and 66 genes with robust biological support. In an independent sample of 1,175,012 self-report ANX cases and 1,956,379 controls, 51 of the 58 associated variants were replicated. As predicted by twin studies, we found substantial genetic correlation between ANX and depression, neuroticism, and other internalizing phenotypes. Follow-up analyses demonstrated enrichment in all major brain regions and highlighted GABAergic signaling as one potential mechanism underlying ANX genetic risk. These results advance our understanding of the genetic architecture of ANX and prioritize genes for functional follow-up studies.
RESUMO
Individual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across genotypes. However, environmental sensitivity genetic variants have proven challenging to detect. GWAS of monozygotic twin differences is a family-based variance analysis method, which is more robust to systemic biases that impact population-based methods. We combined data from up to 21,792 monozygotic twins (10,896 pairs) from 11 studies to conduct the largest GWAS meta-analysis of monozygotic phenotypic differences in children and adolescents/adults for seven psychiatric and neurodevelopmental phenotypes: attention deficit hyperactivity disorder (ADHD) symptoms, autistic traits, anxiety and depression symptoms, psychotic-like experiences, neuroticism, and wellbeing. The SNP-heritability of variance in these phenotypes were estimated (h2: 0% to 18%), but were imprecise. We identified a total of 13 genome-wide significant associations (SNP, gene, and gene-set), including genes related to stress-reactivity for depression, growth factor-related genes for autistic traits and catecholamine uptake-related genes for psychotic-like experiences. Monozygotic twins are an important new source of evidence about the genetics of environmental sensitivity.
RESUMO
Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.
Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/genética , População Branca/genética , Neurobiologia , Loci GênicosRESUMO
ABSTRACT: T-ALL relapse usually occurs early but can occur much later, which has been suggested to represent a de novo leukemia. However, we conclusively demonstrate late relapse can evolve from a pre-leukemic subclone harbouring a non-coding mutation that evades initial chemotherapy.
Assuntos
Leucemia-Linfoma de Células T do Adulto , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Mutação , Recidiva , Doença Crônica , Células ClonaisRESUMO
In the present study, we analyzed a large corpus of English-language online media articles covering genome-wide association studies (GWAS), exemplifying the use of computational methods to study science communication in biological sciences. We analyzed trends in media coverage, readability, themes, and mentions of ethical and social issues, in over 5,000 websites published from 2005 to 2018 from 3,555 GWAS publications on 1,943 different traits, identified via GWAS Catalog using a text-mining approach to inform the discussion about genetic literacy and media coverage. We found that 22.9% of GWAS papers received media attention but most were described in language too complex to be understood by the public. Ethical issues are rarely mentioned and mentions of translation are increasing over time. We predicted media attention based on year of publication, number of genetic associations identified, study sample size, and journal impact factor, using a regression model (r2 = 38.7%). We found that chronotype, educational attainment, alcohol and coffee consumption, sexual orientation, tanning, and hair color received substantially more attention than predicted by the regression model. We also evaluated the prevalence of the clickbait "one gene, one disease" headlines (e.g., "Scientists Say They've Found Gene That Causes Breast Cancer") and found that it is declining. In sum, online media coverage of GWAS should be more accessible, introduce more modern genetics terms, and when appropriate, ELSI should be mentioned. Science communication research can benefit from big data and text-mining techniques which allow us to study trends and changes in coverage trends across thousands of media outlets. Results can be explored interactively in a website we have built for this manuscript: https://jjmorosoli.shinyapps.io/newas/.
Assuntos
Compreensão , Estudo de Associação Genômica Ampla , Masculino , Feminino , Humanos , Comunicação , Idioma , AlfabetizaçãoRESUMO
Posttraumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 novel). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (e.g., GRIA1, GRM8, CACNA1E ), developmental, axon guidance, and transcription factors (e.g., FOXP2, EFNA5, DCC ), synaptic structure and function genes (e.g., PCLO, NCAM1, PDE4B ), and endocrine or immune regulators (e.g., ESR1, TRAF3, TANK ). Additional top genes influence stress, immune, fear, and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.
RESUMO
OBJECTIVE: The Australian Genetics of Bipolar Disorder Study is a nation-wide cohort of adults living with bipolar disorder. The study aims to detect the relationships between genetic risk, symptom severity, and the lifetime prevalence of bipolar disorder, treatment response and medication side effects, and patterns and costs of health care usage. METHODS: A total of 6682 participants (68.3% female; aged 44.8 ± 13.6 years [range = 18-90]) were recruited in three waves: a nation-wide media campaign, a mail-out based on prescriptions for lithium carbonate and through the Australian Genetics of Depression Study. Participants completed a self-report questionnaire. A total of 4706 (70%) participants provided a saliva sample and were genotyped and 5506 (82%) consented to record linkage of their Pharmaceutical and Medicare Benefits Schedule data. RESULTS: Most participants were living with bipolar I disorder (n = 4068) while 1622 participants were living with bipolar II disorder and 992 with sub-threshold bipolar disorder. The mean age of bipolar disorder diagnosis was 32.7 ± 11.6 years but was younger in bipolar I (p = 2.0E-26) and females (p = 5.7E-23). Excluding depression with onset prior to bipolar disorder diagnosis, 64.5% of participants reported one or more co-occurring psychiatric disorders: most commonly generalised anxiety disorder (43.5%) and posttraumatic stress disorder (20.7%). Adverse drug reactions were common and resulted in discontinuation rates ranging from 33.4% for lithium to 63.0% for carbamazepine. CONCLUSION: Our findings highlight the high rate of comorbidities and adverse drug reactions among adults living with bipolar disorder in the general Australian population. Future genomic analyses focus on identifying genetic variants influencing pharmacotherapy treatment response and side effects.
Assuntos
Transtorno Bipolar , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Adulto , Idoso , Feminino , Humanos , Adulto Jovem , Masculino , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/genética , Austrália/epidemiologia , Programas Nacionais de Saúde , Carbonato de LítioRESUMO
Endogenous retroviruses (ERVs) have rewired host gene networks. To explore the origins of co-option, we employed an active murine ERV, IAPEz, and an embryonic stem cell (ESC) to neural progenitor cell (NPC) differentiation model. Transcriptional silencing via TRIM28 maps to a 190 bp sequence encoding the intracisternal A-type particle (IAP) signal peptide, which confers retrotransposition activity. A subset of "escapee" IAPs (â¼15%) exhibits significant genetic divergence from this sequence. Canonical repressed IAPs succumb to a previously undocumented demarcation by H3K9me3 and H3K27me3 in NPCs. Escapee IAPs, in contrast, evade repression in both cell types, resulting in their transcriptional derepression, particularly in NPCs. We validate the enhancer function of a 47 bp sequence within the U3 region of the long terminal repeat (LTR) and show that escapee IAPs convey an activating effect on nearby neural genes. In sum, co-opted ERVs stem from genetic escapees that have lost vital sequences required for both TRIM28 restriction and autonomous retrotransposition.
Assuntos
Retrovirus Endógenos , Proteína 28 com Motivo Tripartido , Animais , Camundongos , Diferenciação Celular , Células-Tronco Embrionárias/metabolismo , Retrovirus Endógenos/genética , Retrovirus Endógenos/metabolismo , Histonas/metabolismo , Proteína 28 com Motivo Tripartido/metabolismo , Sequências Repetidas Terminais/genéticaRESUMO
BACKGROUND: Although associations between maternal exposure to adverse childhood experiences (ACEs) and perinatal anxiety and depression are established, there is a paucity of information about the associations between ACEs and perinatal trauma and perinatal post-traumatic stress outcomes. For the purposes of this article, perinatal trauma is defined as a very frightening or distressing event that may result in psychological harm. The event must have been related to conception, pregnancy, birth, and up to 12 months postpartum. METHODS: Women recruited at an antenatal appointment (n = 262) were invited to complete online surveys at two-time points; mid-pregnancy and eight weeks after the estimated date of delivery. The ACE Q 10-item self-reporting tool and a perinatal trauma screen related to the current and/or a previous perinatal period were completed. If the perinatal trauma screen was positive at either time point in the study, women were invited to complete a questionnaire examining symptoms of perinatal post-traumatic stress disorder and, if consenting, a clinical interview where the Post-traumatic Symptoms Scale was administered. RESULTS: Sixty women (22.9%) reported four or more ACEs. These women were almost four times more likely to endorse perinatal trauma, when compared with those who either did not report ACEs (OR = 3.6, CI 95% 1.74 - 7.36, p < 0.001) or had less than four ACEs (OR = 3.9, CI 95% 2.037.55, p < 0.001). A 6-sevenfold increase in perinatal trauma was seen amongst women who reported having at least one ACE related to abuse (OR = 6.23, CI 95% 3.32-11.63, p < 0.001) or neglect (OR = 6.94, CI 95% 2.95-16.33, p < 0.001). The severity of perinatal-PTSD symptoms for those with perinatal trauma in pregnancy was significantly higher in those women exposed to at least one ACE related to abuse. CONCLUSIONS: Awareness of maternal exposure to childhood adversity/maltreatment is critical to providing trauma-informed approaches in the perinatal setting. Our study suggests that routine screening for ACEs in pregnancy adds clinical value. This adds to previous research confirming the relationship between ACEs and mental health complexities and suggests that ACEs influence perinatal mental health outcomes.
Assuntos
Experiências Adversas da Infância , Maus-Tratos Infantis , Parto , Criança , Feminino , Humanos , Gravidez , Maus-Tratos Infantis/diagnóstico , Estudos Longitudinais , Parto/psicologia , Período Pós-Parto/psicologia , Fatores de Risco , Transtornos de Estresse Pós-TraumáticosRESUMO
PURPOSE: Failure to respond to induction chemotherapy portends a poor outcome in childhood acute lymphoblastic leukemia (ALL) and is more frequent in T-cell ALL (T-ALL) than B-cell ALL. We aimed to address the limited understanding of clinical and genetic factors that influence outcome in a cohort of patients with T-ALL induction failure (IF). METHODS: We studied all cases of T-ALL IF on two consecutive multinational randomized trials, UKALL2003 and UKALL2011, to define risk factors, treatment, and outcomes. We performed multiomic profiling to characterize the genomic landscape. RESULTS: IF occurred in 10.3% of cases and was significantly associated with increasing age, occurring in 20% of patients age 16 years and older. Five-year overall survival (OS) rates were 52.1% in IF and 90.2% in responsive patients (P < .001). Despite increased use of nelarabine-based chemotherapy consolidated by hematopoietic stem-cell transplant in UKALL2011, there was no improvement in outcome. Persistent end-of-consolidation molecular residual disease resulted in a significantly worse outcome (5-year OS, 14.3% v 68.5%; HR, 4.10; 95% CI, 1.35 to 12.45; P = .0071). Genomic profiling revealed a heterogeneous picture with 25 different initiating lesions converging on 10 subtype-defining genes. There was a remarkable abundance of TAL1 noncoding lesions, associated with a dismal outcome (5-year OS, 12.5%). Combining TAL1 lesions with mutations in the MYC and RAS pathways produces a genetic stratifier that identifies patients highly likely to fail conventional therapy (5-year OS, 23.1% v 86.4%; HR, 6.84; 95% CI, 2.78 to 16.78; P < .0001) and who should therefore be considered for experimental agents. CONCLUSION: The outcome of IF in T-ALL remains poor with current therapy. The lack of a unifying genetic driver suggests alternative approaches, particularly using immunotherapy, are urgently needed.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Adulto Jovem , Adolescente , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Resultado do Tratamento , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Linfócitos T , PrognósticoRESUMO
BACKGROUND: Traumatic experiences are associated with increased risk for major depressive disorder (MDD). This study sought to determine the extent that trauma exposure, depression polygenic risk scores (PRS), and their interaction are associated with MDD and individual depression symptoms. METHODS: Data from 102,182 individuals from the large-scale UK Biobank population cohort was analysed. A series of regression analyses were conducted to estimate the association between trauma, depression PRS and 1) current depression, 2) lifetime MDD case-control status, 3) nine individual current depressive symptoms, and 4) thirteen individual symptoms experienced during a major depressive episode. Additive and multiplicative PRS-by-trauma interactions were also assessed. RESULTS: Trauma and depression PRS were significantly associated with both current depression and lifetime MDD. A positive, additive interaction effect was observed on depression, but multiplicative interactions were not significant. Trauma exposure and depression PRS were associated with specific patterns of depression symptoms; Trauma was associated with low self-esteem, suicidal ideation, and atypical (but not typical) neurovegetative symptoms. Additive interaction effects were observed on six out of nine current depressive symptoms. CONCLUSIONS: Trauma exposure and genetic predisposition to depression may lead to particular symptomatology, which may contribute to the extreme clinical heterogeneity observed in individuals with major depression.
Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico , Depressão , Predisposição Genética para Doença , Fatores de Risco , Análise de Regressão , Estudo de Associação Genômica AmplaRESUMO
Samples can be prone to ascertainment and attrition biases. The Australian Genetics of Depression Study is a large publicly recruited cohort (n = 20,689) established to increase the understanding of depression and antidepressant treatment response. This study investigates differences between participants who donated a saliva sample or agreed to linkage of their records compared to those who did not. We observed that older, male participants with higher education were more likely to donate a saliva sample. Self-reported bipolar disorder, ADHD, panic disorder, PTSD, substance use disorder, and social anxiety disorder were associated with lower odds of donating a saliva sample, whereas anorexia was associated with higher odds of donation. Male and younger participants showed higher odds of agreeing to record linkage. Participants with higher neuroticism scores and those with a history of bipolar disorder were also more likely to agree to record linkage whereas participants with a diagnosis of anorexia were less likely to agree. Increased likelihood of consent was associated with increased genetic susceptibility to anorexia and reduced genetic risk for depression, and schizophrenia. Overall, our results show moderate differences among these subsamples. Most current epidemiological studies do not search for attrition biases at the genetic level. The possibility to do so is a strength of samples such as the AGDS. Our results suggest that analyses can be made more robust by identifying attrition biases both on the phenotypic and genetic level, and either contextualising them as a potential limitation or performing sensitivity analyses adjusting for them.
Assuntos
Anorexia , Depressão , Humanos , Masculino , Depressão/epidemiologia , Depressão/genética , Austrália , Consentimento Livre e Esclarecido , DNARESUMO
Genes associated with educational attainment may be related to or interact with adolescent alcohol, tobacco and cannabis use. Potential gene-environment interplay between educational attainment polygenic scores (EA-PGS) and adolescent alcohol, tobacco, and cannabis use was evaluated with a series of regression models fitted to data from a sample of 1871 adult Australian twins. All models controlled for age, age2, cohort, sex and genetic ancestry as fixed effects, and a genetic relatedness matrix was included as a random effect. Although there was no evidence that adolescent alcohol, tobacco or cannabis use interacted with EA-PGS to influence educational attainment, there was a significant, positive gene-environment correlation with adolescent alcohol use at all PGS thresholds (ps <.02). Higher EA-PGS were associated with an increased likelihood of using alcohol as an adolescent (ΔR2 ranged from 0.5% to 1.1%). The positive gene-environment correlation suggests a complex relationship between educational attainment and alcohol use that is due to common genetic factors.
Assuntos
Cannabis , Adulto , Adolescente , Humanos , Nicotiana , Austrália/epidemiologia , Herança Multifatorial/genética , Escolaridade , EtanolRESUMO
Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery samples (N = 85,359) and five independent replication samples (N = 8058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, p = 6.32 × 10-10). Furthermore, we observed intronic variation in Foxp2 and one of its targets (Cntnap2) distinguishing a mouse model of pathological aggression (BALB/cJ strain) from controls (BALB/cByJ strain). Polygenic risk score (PRS) analyses in independent samples revealed that the genetic risk for ASB was associated with several antisocial outcomes across the lifespan, including diagnosis of conduct disorder, official criminal convictions, and trajectories of antisocial development. We found substantial genetic correlations of ASB with mental health (depression rg = 0.63, insomnia rg = 0.47), physical health (overweight rg = 0.19, waist-to-hip ratio rg = 0.32), smoking (rg = 0.54), cognitive ability (intelligence rg = -0.40), educational attainment (years of schooling rg = -0.46) and reproductive traits (age at first birth rg = -0.58, father's age at death rg = -0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB.
Assuntos
Transtorno da Personalidade Antissocial , Transtorno da Conduta , Animais , Camundongos , Transtorno da Personalidade Antissocial/genética , Estudo de Associação Genômica Ampla , Transtorno da Conduta/genética , Transtorno da Conduta/psicologia , Agressão/psicologia , Herança Multifatorial/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genéticaRESUMO
Mammalian genomes are a battleground for genetic conflict between repetitive elements and KRAB-zinc finger proteins (KZFPs). We asked whether KZFPs can regulate cell fate by using ZFP819, which targets a satellite DNA array, ZP3AR. ZP3AR coats megabase regions of chromosome 7 encompassing genes encoding ZSCAN4, a master transcription factor of totipotency. Depleting ZFP819 in mouse embryonic stem cells (mESCs) causes them to transition to a 2-cell (2C)-like state, whereby the ZP3AR array switches from a poised to an active enhancer state. This is accompanied by a global erosion of heterochromatin roadblocks, which we link to decreased SETDB1 stability. These events result in transcription of active LINE-1 elements and impaired differentiation. In summary, ZFP819 and TRIM28 partner up to close chromatin across Zscan4, to promote exit from totipotency. We propose that satellite DNAs may control developmental fate transitions by barcoding and switching off master transcription factor genes.
Assuntos
DNA Satélite , Proteínas Repressoras , Animais , Camundongos , DNA Satélite/genética , Mamíferos/genética , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Repressoras/metabolismo , Fatores de Transcrição/genética , CromossomosRESUMO
Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10-8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10-9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10-8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
Assuntos
Predisposição Genética para Doença , Linfoma não Hodgkin , Humanos , Estudo de Associação Genômica Ampla , Fatores de Risco , Linfoma não Hodgkin/genética , Células Germinativas , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVES: This study sought to evaluate the prevalence, timing of onset and duration of symptoms of depression in the perinatal period (PND) in women with depression, according to whether they had a history of depression prior to their first perinatal period. We further sought to identify biopsychosocial correlates of perinatal symptoms in women with depression. DESIGN AND SETTING: The Australian Genetics of Depression Study is an online case cohort study of the aetiology of depression. For a range of variables, women with depression who report significant perinatal depressive symptoms were compared with women with lifetime depression who did not experience perinatal symptoms. PARTICIPANTS: In a large sample of parous women with major depressive disorder (n=7182), we identified two subgroups of PND cases with and without prior depression history (n=2261; n=878, respectively). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was a positive screen for PND on the lifetime version of the Edinburgh Postnatal Depression Scale. Descriptive measures reported lifetime prevalence, timing of onset and duration of PND symptoms. There were no secondary outcome measures. RESULTS: The prevalence of PND among parous women was 70%. The majority of women reported at least one perinatal episode with symptoms both antenatally and postnatally. Of women who experienced depression prior to first pregnancy, PND cases were significantly more likely to report more episodes of depression (OR=1.15 per additional depression episode, 95% CI 1.13 to 1.17, p<0.001), non-European ancestry (OR 1.5, 95% CI 1.0 to 2.1, p=0.03), severe nausea during pregnancy (OR 1.3, 95% CI 1.1 to 1.6, p=0.006) and emotional abuse (OR 1.4, 95% CI 1.1 to 1.7, p=0.005). CONCLUSIONS: The majority of parous women with lifetime depression in this study experienced PND, associated with more complex, severe depression. Results highlight the importance of perinatal assessments of depressive symptoms, particularly for women with a history of depression or childhood adverse experiences.
Assuntos
Depressão Pós-Parto , Transtorno Depressivo Maior , Austrália/epidemiologia , Criança , Estudos de Coortes , Depressão/psicologia , Depressão Pós-Parto/diagnóstico , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Gravidez , Prevalência , Fatores de RiscoRESUMO
We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.
Assuntos
Abandono do Hábito de Fumar , Gêmeos Monozigóticos , Criança , Escolaridade , Humanos , Fumar/genética , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genéticaRESUMO
Biomarkers may be useful endophenotypes for genetic studies if they share genetic sources of variation with the outcome, for example, with all-cause mortality. Australian adult study participants who had reported their parental survival information were included in the study: 14,169 participants had polygenic risk scores (PRS) from genotyping and up to 13,365 had biomarker results. We assessed associations between participants' biomarker results and parental survival, and between biomarker results and eight parental survival PRS at varying p-value cut-offs. Survival in parents was associated with participants' serum bilirubin, C-reactive protein, HDL cholesterol, triglycerides and uric acid, and with LDL cholesterol for participants' fathers but not for their mothers. PRS for all-cause mortality were associated with liver function tests (alkaline phosphatase, butyrylcholinesterase, gamma-glutamyl transferase), metabolic tests (LDL and HDL cholesterol, triglycerides, uric acid), and acute-phase reactants (C-reactive protein, globulins). Association between offspring biomarker results and parental survival demonstrates the existence of familial effects common to both, while associations between biomarker results and PRS for mortality favor at least a partial genetic cause of this covariation. Identification of genetic loci affecting mortality-associated biomarkers offers a route to the identification of additional loci affecting mortality.