RESUMO
Although currently exotic to New Zealand, the potential geographic distribution of Amblyomma americanum (L.), the lone star tick, was modelled using maximum entropy (MaxEnt). The MaxEnt model was calibrated across the native range of A. americanum in North America using present-day climatic conditions and occurrence data from museum collections. The resulting model was then projected onto New Zealand using both present-day and future climates modelled under two greenhouse gas emission scenarios, representative concentration pathways (RCP) 4.5 (low) and RCP 8.5 (high). Three sets of WorldClim bioclimatic variables were chosen using the jackknife method and tested in MaxEnt using different combinations of model feature class functions and regularization multiplier values. The preferred model was selected based on partial receiver operating characteristic tests, the omission rate and the lowest Akaike information criterion. The final model had four bioclimatic variables, Annual Mean Temperature (BIO1), Annual Precipitation (BIO12), Precipitation Seasonality (BIO15) and Precipitation of Driest Quarter (BIO17), and the projected New Zealand distribution was broadly similar to that of Haemaphysalis longicornis Neumann, New Zealand's only livestock tick, but with a more extensive predicted suitability. The climate change predictions for the year 2050 under both low and high RCP scenarios projected only moderate increases in habitat suitability along the mountain valleys in the South Island. In conclusion, this analysis shows that given the opportunity and license A. americanum could and would successfully establish in New Zealand and could provide another vector for theileriosis organisms.
Assuntos
Distribuição Animal , Clima , Ecossistema , Ixodidae , Animais , Mudança Climática , Entropia , Modelos Teóricos , Nova ZelândiaRESUMO
The North American distributional potential of the recently invaded tick, Haemaphysalis longicornis, was estimated using occurrence data from its geographic range in other parts of the world and relevant climatic data sets. Several hundred candidate models were built using a correlative maximum entropy approach, and best-fitting models were selected based on statistical significance, predictive ability, and complexity. The median of the best-fitting models indicates a broad potential distribution for this species, but restricted to three sectors-the southeastern United States, the Pacific Northwest, and central and southern Mexico.
Assuntos
Distribuição Animal , Espécies Introduzidas , Ixodidae/fisiologia , Infestações por Carrapato , Animais , América do NorteRESUMO
The diathesis-stress theory for depression states that the effects of stress on the depression risk are dependent on the diathesis or vulnerability, implying multiplicative interactive effects on the liability scale. We used polygenic risk scores for major depressive disorder (MDD) calculated from the results of the most recent analysis from the Psychiatric Genomics Consortium as a direct measure of the vulnerability for depression in a sample of 5221 individuals from 3083 families. In the same we also had measures of stressful life events and social support and a depression symptom score, as well as DSM-IV MDD diagnoses for most individuals. In order to estimate the variance in depression explained by the genetic vulnerability, the stressors and their interactions, we fitted linear mixed models controlling for relatedness for the whole sample as well as stratified by sex. We show a significant interaction of the polygenic risk scores with personal life events (0.12% of variance explained, P-value=0.0076) contributing positively to the risk of depression. Additionally, our results suggest possible differences in the aetiology of depression between women and men. In conclusion, our findings point to an extra risk for individuals with combined vulnerability and high number of reported personal life events beyond what would be expected from the additive contributions of these factors to the liability for depression, supporting the multiplicative diathesis-stress model for this disease.
Assuntos
Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/genética , Adulto , Depressão/diagnóstico , Depressão/genética , Transtorno Depressivo Maior/etiologia , Suscetibilidade a Doenças , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Acontecimentos que Mudam a Vida , Masculino , Pessoa de Meia-Idade , Herança Multifatorial/genética , Fatores de RiscoRESUMO
Despite moderate heritability, only one study has identified genome-wide significant loci for cannabis-related phenotypes. We conducted meta-analyses of genome-wide association study data on 2080 cannabis-dependent cases and 6435 cannabis-exposed controls of European descent. A cluster of correlated single-nucleotide polymorphisms (SNPs) in a novel region on chromosome 10 was genome-wide significant (lowest P=1.3E-8). Among the SNPs, rs1409568 showed enrichment for H3K4me1 and H3K427ac marks, suggesting its role as an enhancer in addiction-relevant brain regions, such as the dorsolateral prefrontal cortex and the angular and cingulate gyri. This SNP is also predicted to modify binding scores for several transcription factors. We found modest evidence for replication for rs1409568 in an independent cohort of African American (896 cases and 1591 controls; P=0.03) but not European American (EA; 781 cases and 1905 controls) participants. The combined meta-analysis (3757 cases and 9931 controls) indicated trend-level significance for rs1409568 (P=2.85E-7). No genome-wide significant loci emerged for cannabis dependence criterion count (n=8050). There was also evidence that the minor allele of rs1409568 was associated with a 2.1% increase in right hippocampal volume in an independent sample of 430 EA college students (fwe-P=0.008). The identification and characterization of genome-wide significant loci for cannabis dependence is among the first steps toward understanding the biological contributions to the etiology of this psychiatric disorder, which appears to be rising in some developed nations.
Assuntos
Cromossomos Humanos Par 10/genética , Abuso de Maconha/genética , Adulto , Negro ou Afro-Americano/genética , Alelos , Cannabis , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , População Branca/genética , Adulto JovemRESUMO
Haemaphysalis longicornis is the only species of tick present in New Zealand which infests livestock and is also the only competent vector for Theileria orientalis. Since 2012, New Zealand has suffered from an epidemic of infectious bovine anaemia associated with T. orientalis, an obligate intracellular protozoan parasite of cattle and buffaloes. The aim of this study was to predict the spatial distribution of habitat suitability of New Zealand for the tick H. longicornis using a simple rule-based climate envelope model, to validate the model against published data and use the validated model to project an expansion in habitat suitability for H. longicornis under two alternative climate change scenarios for the periods 2046-2065 and 2081-2100, relative to the climate of 1981-2010. A rule-based climate envelope model was developed based on the environmental requirements for off-host tick survival. The resulting model was validated against a maximum entropy environmental niche model of environmental suitability for T. orientalis transmission and against a H. longicornis occurrence map. Validation was completed using the I-similarity statistic and by linear regression. The H. longicornis climate envelope model predicted that 75% of cattle farms in the North Island, 3% of cattle farms in the South Island and 54% of cattle farms in New Zealand overall have habitats potentially suitable for the establishment of H. longicornis. The validation methods showed an acceptable level of agreement between the envelope model and published data. Both of the climate change scenarios, for each of the time periods, projected only slight to moderate increases in the average farm habitat suitability scores for all the South Island regions. However, only for the West Coast, Marlborough, Tasman, and Nelson regions did these increases in environmental suitability translate into an increased proportion of cattle farms with low or high H. longicornis habitat suitability. These results will have important implications for the geographical progression of Theileria-associated bovine anaemia (TABA) in New Zealand and will also be of interest to Haemaphysalis longicornis researchers in Australia, Japan, Korea and New Zealand.
Assuntos
Distribuição Animal , Mudança Climática , Ecossistema , Ixodidae/fisiologia , Modelos Biológicos , Animais , Previsões , Nova ZelândiaRESUMO
Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.
Assuntos
Povo Asiático/genética , Transtorno Depressivo Maior/genética , População Branca/genética , Teorema de Bayes , Estudos de Casos e Controles , China , Europa (Continente) , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Herança Multifatorial , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The tick-borne haemoparasite Theileria orientalis is the most important infectious cause of anaemia in New Zealand cattle. Since 2012 a previously unrecorded type, T. orientalis type 2 (Ikeda), has been associated with disease outbreaks of anaemia, lethargy, jaundice and deaths on over 1000 New Zealand cattle farms, with most of the affected farms found in the upper North Island. The aim of this study was to model the relative environmental suitability for T. orientalis transmission throughout New Zealand, to predict the proportion of cattle farms potentially suitable for active T. orientalis infection by region, island and the whole of New Zealand and to estimate the average relative environmental suitability per farm by region, island and the whole of New Zealand. The relative environmental suitability for T. orientalis transmission was estimated using the Maxent (maximum entropy) modelling program. The Maxent model predicted that 99% of North Island cattle farms (n=36,257), 64% South Island cattle farms (n=15,542) and 89% of New Zealand cattle farms overall (n=51,799) could potentially be suitable for T. orientalis transmission. The average relative environmental suitability of T. orientalis transmission at the farm level was 0.34 in the North Island, 0.02 in the South Island and 0.24 overall. The study showed that the potential spatial distribution of T. orientalis environmental suitability was much greater than presumed in the early part of the Theileria associated bovine anaemia (TABA) epidemic. Maximum entropy offers a computer efficient method of modelling the probability of habitat suitability for an arthropod vectored disease. This model could help estimate the boundaries of the endemically stable and endemically unstable areas for T. orientalis transmission within New Zealand and be of considerable value in informing practitioner and farmer biosecurity decisions in these respective areas.
Assuntos
Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/transmissão , Meio Ambiente , Modelos Biológicos , Theileriose/epidemiologia , Theileriose/transmissão , Animais , Bovinos , Entropia , Nova Zelândia , Theileria/fisiologiaRESUMO
Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was associated with AO-AD and other aspects of alcohol consumption in two independent samples. Genetic risk scores (GRS) were created based on AO-AD GWAS results from a discovery sample of 1788 regular drinkers from extended pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA). GRS were used to predict AO-AD, AD and Alcohol dependence symptom count (AD-SX), age at onset of intoxication (AO-I), as well as maxdrinks in regular drinking participants from two independent samples-the Study of Addictions: Genes and Environment (SAGE; n=2336) and an Australian sample (OZ-ALC; n=5816). GRS for AO-AD from COGA explained a modest but significant proportion of the variance in all alcohol-related phenotypes in SAGE. Despite including effect sizes associated with large numbers of single nucleotide polymorphisms (SNPs; >110 000), GRS explained, at most, 0.7% of the variance in these alcohol measures in this independent sample. In OZ-ALC, significant but even more modest associations were noted with variance estimates ranging from 0.03 to 0.16%. In conclusion, there is modest evidence that genetic variation in AO-AD is associated with liability to other aspects of alcohol involvement.
Assuntos
Alcoolismo/genética , Adulto , Idade de Início , Austrália , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial , Linhagem , Fenótipo , Estados Unidos , População BrancaRESUMO
Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40-48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32 330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13-20% (P<0.001) of the liability of lifetime cannabis use. Finally, there was a strong genetic correlation (rg=0.83; P=1.85 × 10(-8)) between lifetime cannabis use and lifetime cigarette smoking implying that the SNP effect sizes of the two traits are highly correlated. This is the largest meta-analysis of cannabis GWA studies to date, revealing important new insights into the genetic pathways of lifetime cannabis use. Future functional studies should explore the impact of the identified genes on the biological mechanisms of cannabis use.
Assuntos
Abuso de Maconha/genética , Fumar Maconha/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno CD56/genética , Proteínas de Transporte/genética , Moléculas de Adesão Celular/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Canais de Potássio/genética , Canais de Potássio Ativados por Sódio , Adulto JovemRESUMO
INTRODUCTION: To examine the contribution of trauma exposure to cannabis initiation and transition to first cannabis use disorder (CUD) symptom in African-American (AA) and European-American (EA) emerging adults. METHODS: Data are from the Missouri Adolescent Female Twins Study [(N=3787); 14.6% AA; mean age=21.7 (SD 3.8)]. Trauma exposures (e.g. sexual abuse, physical abuse, witnessing another person being killed or injured, experiencing an accident, and experiencing a disaster) were modeled as time-varying predictors of cannabis initiation and transition to CUD symptom using Cox proportional hazards regression. Other substance involvement and psychiatric disorders were considered as time-varying covariates. RESULTS: Analyses revealed different trauma-related and psychiatric predictors for cannabis use supporting racially distinct etiologic models of cannabis involvement. For AA women, history of witnessing injury/death or experiencing a life-threatening accident was associated with cannabis initiation across the complete emerging adult risk period while sexual abuse predicted cannabis initiation only before 15 years old. For EA women, history of sexual or physical abuse and major depressive disorder (MDD) predicted cannabis initiation and physical abuse and MDD predicted transition from initiation to first CUD symptom. No association was discovered between trauma exposures and transition to first CUD symptom in AA women. CONCLUSIONS: Results reveal trauma exposures as important contributors to cannabis initiation and to a lesser extent transition to CUD symptom, with different trauma types conferring risk for cannabis involvement in AA and EA women. Findings suggest the importance of considering racial/ethnic differences when developing etiologic models of cannabis involvement.
Assuntos
Adultos Sobreviventes de Eventos Adversos na Infância/psicologia , Negro ou Afro-Americano/psicologia , Acontecimentos que Mudam a Vida , Abuso de Maconha/diagnóstico , Abuso de Maconha/psicologia , Fumar Maconha/psicologia , Gêmeos/psicologia , População Branca/psicologia , Adolescente , Adulto , Feminino , Humanos , Prognóstico , Estados Unidos , Adulto JovemRESUMO
Anxiety disorders (ADs), namely generalized AD, panic disorder and phobias, are common, etiologically complex conditions with a partially genetic basis. Despite differing on diagnostic definitions based on clinical presentation, ADs likely represent various expressions of an underlying common diathesis of abnormal regulation of basic threat-response systems. We conducted genome-wide association analyses in nine samples of European ancestry from seven large, independent studies. To identify genetic variants contributing to genetic susceptibility shared across interview-generated DSM-based ADs, we applied two phenotypic approaches: (1) comparisons between categorical AD cases and supernormal controls, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. We used logistic and linear regression, respectively, to analyze the association between these phenotypes and genome-wide single nucleotide polymorphisms. Meta-analysis for each phenotype combined results across the nine samples for over 18 000 unrelated individuals. Each meta-analysis identified a different genome-wide significant region, with the following markers showing the strongest association: for case-control contrasts, rs1709393 located in an uncharacterized non-coding RNA locus on chromosomal band 3q12.3 (P=1.65 × 10(-8)); for FS, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P=2.86 × 10(-9)). Independent replication and further exploration of these findings are needed to more fully understand the role of these variants in risk and expression of ADs.
Assuntos
Transtornos de Ansiedade/genética , Estudos de Casos e Controles , Estudos de Associação Genética/métodos , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , População Branca/genéticaRESUMO
Monitoring an epidemic of an emerging vector-borne disease can be problematic; particularly in a country where vector-borne disease has previously had minimal impact on livestock. This paper describes methods of past and current surveillance of the Theileria-associated bovine anaemia (Ikeda; TABA) epidemic in New Zealand, and the resulting inferences made. Over the three year period of the TABA epidemic a portfolio of surveillance methods has been used: case reporting (with subsidised PCR testing), syndromic surveillance, sentinel surveillance, testing convenience samples for herd infection, as well as specific active surveillance initiatives to understand the tick vector distribution. Surveillance data have shown that the number of affected cattle herds has continued to increase over time with seasonal peaks in spring and autumn coinciding with peak activity of nymph and adult ticks respectively. In spring 2014, the epidemic extended south into areas that were previously considered to be unsuitable for the tick vector. As a result a survey was initiated that showed that ticks were present in areas outside of the known distribution. Testing pooled blood samples from cattle herds across New Zealand showed there still remained a significant percentage of herds where only non-Ikeda type infections were present, indicating that these herds were at risk of future TABA (Ikeda) outbreaks. For some regions there had been a noticeable increase in the percentage of herds infected, yet with only a small increase in the number of outbreaks compared with the previous year. Thus, outbreaks had either gone unobserved or had not been confirmed by testing. In these regions extensive low-input beef farming could explain the non-detection observed. There was a close relationship between the number of syndromic reports of anaemia and the number of confirmed cases of TABA (Ikeda), (P<0.01, adjusted R-squared=0.74). Active monitoring of the epidemic for a three year period has provided valuable insight into seasonal nature of the disease and its continuing impact. Information from multiple surveillance sources can help build up an understanding of the epidemiology, even when data from each individual surveillance stream are limited. The TABA (Ikeda) epidemic in New Zealand represents a useful case study of long term monitoring where disease is caused by an emerging pathogen.
Assuntos
Anemia/veterinária , Epidemias/veterinária , Theileriose/epidemiologia , Anemia/epidemiologia , Anemia/parasitologia , Animais , Bovinos , Monitoramento Epidemiológico , Nova Zelândia/epidemiologia , Estações do Ano , Theileriose/parasitologiaRESUMO
Opioid dependence, a severe addictive disorder and major societal problem, has been demonstrated to be moderately heritable. We conducted a genome-wide association study in Comorbidity and Trauma Study data comparing opioid-dependent daily injectors (N=1167) with opioid misusers who never progressed to daily injection (N=161). The strongest associations, observed for CNIH3 single-nucleotide polymorphisms (SNPs), were confirmed in two independent samples, the Yale-Penn genetic studies of opioid, cocaine and alcohol dependence and the Study of Addiction: Genetics and Environment, which both contain non-dependent opioid misusers and opioid-dependent individuals. Meta-analyses found five genome-wide significant CNIH3 SNPs. The A allele of rs10799590, the most highly associated SNP, was robustly protective (P=4.30E-9; odds ratio 0.64 (95% confidence interval 0.55-0.74)). Epigenetic annotation predicts that this SNP is functional in fetal brain. Neuroimaging data from the Duke Neurogenetics Study (N=312) provide evidence of this SNP's in vivo functionality; rs10799590 A allele carriers displayed significantly greater right amygdala habituation to threat-related facial expressions, a phenotype associated with resilience to psychopathology. Computational genetic analyses of physical dependence on morphine across 23 mouse strains yielded significant correlations for haplotypes in CNIH3 and functionally related genes. These convergent findings support CNIH3 involvement in the pathophysiology of opioid dependence, complementing prior studies implicating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate system.
Assuntos
Predisposição Genética para Doença , Transtornos Relacionados ao Uso de Opioides/genética , Polimorfismo de Nucleotídeo Único , Receptores de AMPA/genética , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiopatologia , Animais , Feminino , Estudo de Associação Genômica Ampla , Habituação Psicofisiológica/genética , Habituação Psicofisiológica/fisiologia , Humanos , Masculino , Camundongos Endogâmicos , Transtornos Relacionados ao Uso de Opioides/diagnóstico por imagem , Transtornos Relacionados ao Uso de Opioides/fisiopatologia , Receptores de AMPA/metabolismo , Especificidade da Espécie , Adulto JovemRESUMO
BACKGROUND: Childhood maltreatment (CM) has consistently been linked with adverse outcomes including substance use disorders and adult sexual revictimization. Adult sexual victimization itself has been linked with psychopathology but has predominately been studied in women. The current investigation examines the impact of CM and co-occurring psychopathology on adult sexual victimization in men and women, replicating findings in three distinct samples. METHOD: We investigated the association between continuous CM factor scores and adult sexual victimization in the Childhood Trauma Study (CTS) sample (N = 2564). We also examined the unique relationship between childhood sexual abuse (CSA) and adult sexual victimization while adjusting for co-occurring substance dependence and psychopathology. We replicated these analyses in two additional samples: the Comorbidity and Trauma Study (CATS; N = 1981) and the Australian Twin-Family Study of Alcohol Use Disorders (OZ-ALC; N = 1537). RESULTS: Analyses revealed a significant association with CM factor scores and adult sexual victimization for both men and women across all three samples. The CSA factor score was strongly associated with adult sexual victimization after adjusting for substance dependence and psychopathology; higher odds ratios were observed in men (than women) consistently across the three samples. CONCLUSIONS: A continuous measure of CSA is independently associated with adult sexual trauma risk across samples in models that included commonly associated substance dependence and psychopathology as covariates. The strength of the association between this CSA measure and adult sexual victimization is higher in magnitude for men than women, pointing to the need for further investigation of sexual victimization in male community samples.
Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Sobreviventes Adultos de Maus-Tratos Infantis/estatística & dados numéricos , Abuso Sexual na Infância/psicologia , Delitos Sexuais/psicologia , Adulto , Austrália , Criança , Comorbidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores Sexuais , Fatores Socioeconômicos , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
BACKGROUND: Genetic influences contribute significantly to co-morbidity between conduct disorder and substance use disorders. Estimating the extent of overlap can assist in the development of phenotypes for genomic analyses. METHOD: Multivariate quantitative genetic analyses were conducted using data from 9577 individuals, including 3982 complete twin pairs and 1613 individuals whose co-twin was not interviewed (aged 24-37 years) from two Australian twin samples. Analyses examined the genetic correlation between alcohol dependence, nicotine dependence and cannabis abuse/dependence and the extent to which the correlations were attributable to genetic influences shared with conduct disorder. RESULTS: Additive genetic (a(2) = 0.48-0.65) and non-shared environmental factors explained variance in substance use disorders. Familial effects on conduct disorder were due to additive genetic (a(2) = 0.39) and shared environmental (c(2) = 0.15) factors. All substance use disorders were influenced by shared genetic factors (rg = 0.38-0.56), with all genetic overlap between substances attributable to genetic influences shared with conduct disorder. Genes influencing individual substance use disorders were also significant, explaining 40-73% of the genetic variance per substance. CONCLUSIONS: Among substance users in this sample, the well-documented clinical co-morbidity between conduct disorder and substance use disorders is primarily attributable to shared genetic liability. Interventions targeted at generally reducing deviant behaviors may address the risk posed by this shared genetic liability. However, there is also evidence for genetic and environmental influences specific to each substance. The identification of these substance-specific risk factors (as well as potential protective factors) is critical to the future development of targeted treatment protocols.
Assuntos
Transtorno da Conduta/genética , Doenças em Gêmeos/genética , Interação Gene-Ambiente , Transtornos Relacionados ao Uso de Substâncias/genética , Gêmeos/genética , Adolescente , Adulto , Austrália , Cannabis , Criança , Comorbidade , Etanol , Feminino , Humanos , Masculino , Análise Multivariada , Nicotina , Fenótipo , Sistema de Registros , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: In the present study, we examined the relationship between cannabis involvement and suicidal ideation (SI), plan and attempt, differentiating the latter into planned and unplanned attempt, taking into account other substance involvement and psychopathology. METHODS: We used two community-based twin samples from the Australian Twin Registry, including 9583 individuals (58.5% female, aged between 27 and 40). The Semi-Structured Assessment of the Genetics of Alcoholism (SSAGA) was used to assess cannabis involvement which was categorized into: (0) no cannabis use (reference category); (1) cannabis use only; (2) 1-2 cannabis use disorder symptoms; (3) 3 or more symptoms. Separate multinomial logistic regression analyses were conducted for SI and suicide attempt with or without a plan. Twin analyses examined the genetic overlap between cannabis involvement and SI. RESULTS: All levels of cannabis involvement were related to SI, regardless of duration (odds ratios [ORs]=1.28-2.00, p<0.01). Cannabis use and endorsing ≥3 symptoms were associated with unplanned (SANP; ORs=1.95 and 2.51 respectively, p<0.05), but not planned suicide attempts (p>0.10). Associations persisted even after controlling for other psychiatric disorders and substance involvement. Overlapping genetic (rG=0.45) and environmental (rE=0.21) factors were responsible for the covariance between cannabis involvement and SI. CONCLUSIONS: Cannabis involvement is associated, albeit modestly, with SI and unplanned suicide attempts. Such attempts are difficult to prevent and their association with cannabis use and cannabis use disorder symptoms requires further study, including in different samples and with additional attention to confounders.
Assuntos
Abuso de Maconha/psicologia , Fumar Maconha/psicologia , Ideação Suicida , Tentativa de Suicídio/psicologia , Suicídio/psicologia , Adulto , Austrália , Feminino , Humanos , Masculino , Gêmeos/psicologia , Prevenção do SuicídioRESUMO
Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.
Assuntos
Dissonias/genética , Sono/genética , Adulto , Negro ou Afro-Americano/genética , Idoso , Feminino , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Autorrelato , População Branca/genéticaRESUMO
The last 50 years of research into infections in Australia and New Zealand caused by larvae of the sheep blowfly, Lucilia cuprina, have significantly advanced our understanding of this blowfly and its primary host, the sheep. However, apart from some highly effective drugs it could be argued that no new control methodologies have resulted. This review addresses the major areas of sheep blowfly research over this period describing the significant outcomes and analyses, and what is still required to produce new commercial control technologies. The use of drugs against this fly species has been very successful but resistance has developed to almost all current compounds. Integrated pest management is becoming basic to control, especially in the absence of mulesing, and has clearly benefited from computer-aided technologies. Biological control has more challenges but natural and perhaps transformed biopesticides offer possibilities for the future. Experimental vaccines have been developed but require further analysis of antigens and formulations to boost protection. Genetic technologies may provide potential for long-term control through more rapid indirect selection of sheep less prone to flystrike. Finally in the future, genetic analysis of the fly may allow suppression and perhaps eradication of blowfly populations or identification of new and more viable targets for drug and vaccine intervention. Clearly all these areas of research offer potential new controls but commercial development is perhaps inhibited by the success of current chemical insecticides and certainly requires a significant additional injection of resources.
Assuntos
Dípteros , Controle de Insetos , Miíase/veterinária , Doenças dos Ovinos/prevenção & controle , Animais , Austrália , Dípteros/genética , Dípteros/imunologia , Dípteros/fisiologia , Controle de Insetos/métodos , Controle de Insetos/tendências , Resistência a Inseticidas , Inseticidas , Larva , Miíase/imunologia , Miíase/prevenção & controle , Nova Zelândia , Controle Biológico de Vetores , Ovinos , Doenças dos Ovinos/imunologia , VacinasRESUMO
Cannabis is the most commonly used illicit drug worldwide. With debate surrounding the legalization and control of use, investigating its health risks has become a pressing area of research. One established association is that between cannabis use and schizophrenia, a debilitating psychiatric disorder affecting ~1% of the population over their lifetime. Although considerable evidence implicates cannabis use as a component cause of schizophrenia, it remains unclear whether this is entirely due to cannabis directly raising risk of psychosis, or whether the same genes that increases psychosis risk may also increase risk of cannabis use. In a sample of 2082 healthy individuals, we show an association between an individual's burden of schizophrenia risk alleles and use of cannabis. This was significant both for comparing those who have ever versus never used cannabis (P=2.6 × 10(-4)), and for quantity of use within users (P=3.0 × 10(-3)). Although directly predicting only a small amount of the variance in cannabis use, these findings suggest that part of the association between schizophrenia and cannabis is due to a shared genetic aetiology. This form of gene-environment correlation is an important consideration when calculating the impact of environmental risk factors, including cannabis use.