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Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.

Substance use disorders (SUDs) incur serious social and personal costs. The risk for SUDs is complex, with risk factors ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N = 15,134. Our analyses included participants of European (NEUR = 12,659) and African (NAFR = 2475) ancestries. SUD outcomes included: (1) alcohol dependence, (2) nicotine dependence; (3) drug dependence, and (4) any substance dependence. In the models containing the PGS and CERI, the CERI was associated with all three outcomes (ORs = 01.37-1.67). PGS for problematic alcohol use, externalizing, and smoking quantity were associated with alcohol dependence, drug dependence, and nicotine dependence, respectively (OR = 1.11-1.33). PGS for problematic alcohol use and externalizing were also associated with any substance dependence (ORs = 1.09-1.18). The full model explained 6-13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.86-8.04 for each SUD relative to the bottom 90%. Overall, the combined measures of clinical, environmental, and genetic risk demonstrated modest ability to distinguish between affected and unaffected individuals in young adulthood. PGS were significant but added little in addition to the clinical/environmental risk index. Results from our analysis demonstrate there is still considerable work to be done before tools such as these are ready for clinical applications.

In response to international agreements, recent Indian legislation has raised expectations that all children, regardless of need or ability, should gain access to formal education that is inclusive and addresses their social and learning needs. Initiatives designed to support the implementation of this legislation have been undertaken in several parts of India. Reports related to such initiatives have largely focused upon developments in large urban connotations, with studies in rural areas being less in evidence. This paper reports a small-scale study conducted in Telangana a state in the south-central part of India. Through the application of semi-structured interviews data were obtained to enable a comparison to be made of the experiences of two purposive samples of families of children with disabilities and special educational needs, and the professionals who support them. The first sample was located in Hyderabad, a large metropolitan city, the capital of Telangana State. The second was situated in villages in Sangareddy, a single rural district of the same state. Interviews were conducted either in English or in Telugu, the state language with all interviews transcribed and subjected to thematic analysis. The findings, which will be used to support further development in the area, reveal a willingness on the part of professionals to support the education and social welfare needs of children with special educational needs and their families and an awareness of current national legislation aimed at achieving this objective. A disparity exists between the availability of professional support services available to families and children, with those living in the rural district experiencing greater difficulty in accessing appropriate support than their counterparts in the metropolitan city. The lack of opportunities for training and professional development is perceived to be a major obstacle to the progress of inclusive education as required by national legislation in both locations. Recommendations are made for further research that is closely allied to changes in practice, for the development of professional development of teachers and other professionals, and for the development of centralised provision in rural areas to address the needs of families.

ObjectiveTo investigate the genetic architecture of internalizing symptoms in childhood and adolescence.MethodIn 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument.ResultsThe meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, neffective = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (|rg| > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |rg| = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa.ConclusionGenetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E-06), PCDH7 (P = 2.0E-06), and IPO13 (P = 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range [Formula: see text]: 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.

Data were collected from heads of households across Bhutan to gain insights regarding children with disabilities up to 18 years in Bhutan. Fieldwork was conducted by local enumerators, trained by researchers from the UK who analysed and interpreted the data. Results indicate that whilst there are largely positive attitudes towards children with disabilities in Bhutan, the majority of respondents conceptualized disability narrowly and were pessimistic about such children's ability to lead full lives. Households including children with disabilities were less positive than others concerning the ways in which children are regarded and supported in their communities. Fatalistic views related to beliefs in karma were noted and influenced expectations regarding what children with disabilities might achieve. More positive attitudes are held by younger people and those more highly educated. Attitudes and expectations have had a negative effect in restricting access to educational and social inclusion for many children with disabilities.

This paper reports the opportunities and challenges faced by first generation learners, all of whom were designated as being from scheduled tribes and scheduled castes, accessing education in a rural community in the state of Maharashtra, India. The design of the research and the methods used for this child-centred study aimed to generate data to enable reflection on the real-life complexities experienced by children in this situation. Ten case studies based around individual children who shared common experiences were developed. These children had attended the local Zilla Parishad School (Government funded school) in the past and were enrolled at a Non-Governmental Organisation (NGO) funded school at the time of the investigation. The ten case studies focused on those antecedents, contextual factors, perceptions and attitudes towards education that had shaped the experiences of the children. Their personal circumstances, opportunities and challenges emanating from their social, economic, cultural and political environments are discussed.

Genome-wide, polygenic risk scores (PRS) have emerged as a useful way to characterize genetic liability. There is growing evidence that PRS may prove useful for early identification of those at increased risk for certain diseases. The current potential of PRS for alcohol use disorders (AUD) remains an open question. Using data from both a population-based sample [the FinnTwin12 (FT12) study] and a high-risk sample [the Collaborative Study on the Genetics of Alcoholism (COGA)], we examined the association between PRSs derived from genome-wide association studies (GWASs) of (1) alcohol dependence/alcohol problems, (2) alcohol consumption, and (3) risky behaviors with AUD and other substance use disorder (SUD) criteria. These PRSs explain ~2.5-3.5% of the variance in AUD (across FT12 and COGA) when all PRSs are included in the same model. Calculations of area under the curve (AUC) show PRS provide only a slight improvement over a model with age, sex, and ancestral principal components as covariates. While individuals in the top 20, 10, and 5% of the PRS distribution had greater odds of having an AUD compared to the lower end of the continuum in both COGA and FT12, the point estimates at each threshold were statistically indistinguishable. Those in the top 5% reported greater levels of licit (alcohol and nicotine) and illicit (cannabis and opioid) SUD criteria. PRSs are associated with risk for SUD in independent samples. However, usefulness for identifying those at increased risk in their current form is modest, at best. Improvement in predictive ability will likely be dependent on increasing the size of well-phenotyped discovery samples.

In recent years, international initiatives such as the Salamanca Statement and Framework for Action on Special Needs Education (UNESCO, 1994) and the Sustainable Development Goals (United Nations General Assembly, 2015) have encouraged educational researchers to focus their attentions on those conditions that enable schools to become more inclusive. Much of this research has focused upon teacher attitudes and expectations (Unianu, 2012), the development of inclusive pedagogical approaches (Florian & Black Hawkins, 2011), and aspects of assessment and classroom management (Erickson & Davis, 2015). Less attention has been given to the experiences of children with special educational needs as learners in mainstream classrooms. In this paper, drawing upon data from interviews conducted with children during a four year longitudinal study, (Project Iris--Inclusive Research in Irish Schools), we consider the relationship between acceptance and belonging as critical factors in defining what it means to be included in school. In addition to presenting data from children in 24 schools across Ireland, we will discuss the challenges of undertaking fair analysis that ensures that the researchers' interpretation of pupil voices can be seen as trustworthy and informed. The paper concludes with a discussion of the principles that might inform the ways in which researchers can work with children in order to ensure them fair representation in research that investigates critical aspects of their lives.

Paraprofessional support to enable access to education has developed in differing directions in a range of countries. In Ireland, the role of the special needs assistant has focused on supporting the additional care needs of children with special educational needs to ensure their participation in lessons. The role of the special needs assistant (SNA) was considered crucial as Irish mainstream schools adapted to delivering more inclusive learning environments. Support provision has been recently reconceptualised and within this model special needs assistants are now designated as Inclusion Support Assistants with a very specific care role excluding any teaching activity. This research draws on data from a longitudinal study of SEN provision with a specific focus on the role of SNAs within Irish schools. Findings indicated that the contribution of special needs assistants was highly valued by education stakeholders. It is suggested that the evolution of the SNA role in Ireland can support schools in adopting a flexible approach to create inclusive learning environments.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures.

Background and aimsCannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants.MethodsA twin-based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome-wide association meta-analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals.ResultsThe twin-based heritability for age at first cannabis use was 38% [95% confidence interval (CI) = 19-60%]. Shared and unique environmental factors explained 39% (95% CI = 20-56%) and 22% (95% CI = 16-29%). The genome-wide association meta-analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium-transporting ATPase gene (ATP2C2) at P  0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant.ConclusionAge at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.