Research Review: A guide to computing and implementing polygenic scores in developmental research

The increasing availability of genotype data in longitudinal population- and family-based samples provides opportunities for using polygenic scores (PGS) to study developmental questions in child and adolescent psychology and psychiatry. Here, we aim to provide a comprehensive overview of how PGS can be generated and implemented in developmental psycho(patho)logy, with a focus on longitudinal designs. As such, the paper is organized into three parts: First, we provide a formal definition of polygenic scores and related concepts, focusing on assumptions and limitations. Second, we give a general overview of the methods used to compute polygenic scores, ranging from the classic approach to more advanced methods. We include recommendations and reference resources available to researchers aiming to conduct PGS analyses. Finally, we focus on the practical applications of PGS in the analysis of longitudinal data. We describe how PGS have been used to research developmental outcomes, and how they can be applied to longitudinal data to address developmental questions

Perinatal insults and neurodevelopmental disorders may impact Huntington's disease age of diagnosis

Introduction: The age of diagnosis of Huntington's disease (HD) varies among individuals with the same HTT CAG-repeat expansion size. We investigated whether early-life events, like perinatal insults or neurodevelopmental disorders, influence the diagnosis age. Methods: We used data from 13,856 participants from REGISTRY and Enroll-HD, two large international multicenter observational studies. Disease-free survival analyses of mutation carriers with an HTT CAG repeat expansion size above and including 36 were computed through Kaplan-Meier estimates of median time until an HD diagnosis. Comparisons between groups were computed using a Cox proportional hazard survival model adjusted for CAG-repeat expansion length. We also assessed whether the group effect depended on gender and the affected parent. Results: Insults in the perinatal period were associated with an earlier median age of diagnosis of 45.00 years (95%CI: 42.07–47.92) compared to 51.00 years (95%CI: 50.68–51.31) in the reference group, with a CAG-adjusted hazard ratio of 1.61 (95%CI: 1.26–2.06). Neurodevelopmental disorders were also associated with an earlier median age of diagnosis than the reference group of 47.00 years (95% CI: 43.38–50.62) with a CAG-adjusted hazard ratio of 1.42 (95%CI: 1.16–1.75). These associations did not change significantly with gender or affected parent. Conclusions: These results, derived from large observational datasets, show that perinatal insults and neurodevelopmental disorders are associated with earlier ages of diagnosis of magnitudes similar to the effects of known genetic modifiers of HD. Given their clear temporal separation, these early events may be causative of earlier HD onset, but further research is needed to prove causation

Rapid, progressive neuropathic arthropathy of the hip in a patient co-infected with human immunodeficiency virus, hepatitis C virus and tertiary syphilis: case report

BACKGROUND: Syphilis is a chronic infection that is classified into three stages. In its tertiary stage, syphilis spreads to the brain, heart and other organs; the lesions may involve the skin, mucous membranes and bones. Neuropathic arthropathy associated with tertiary syphilis has rarely been described in Europe and its association with HIV-HCV co-infection has not been reported so far.This article reports the case of a man with tertiary syphilis presenting with rapidly evolving neuropathic arthropathy of the hip and extensive bone destruction. CASE PRESENTATION: On initial presentation, the patient complained of progressively worsening left-sided coxalgia without localized or generalized inflammation. The patient reported to have no history of previous infections, trauma or cancer. Plain x-ray films of the left coxofemoral joint showed marked degeneration with necrosis of the proximal epiphysis of femur and morphological alterations of the acetabulum without protrusion. Primary coxarthrosis was diagnosed and hip arthroplasty was offered, but the patient declined treatment. Three months later, the patient presented a marked deterioration of his general condition. He disclosed that he was seropositive for HCV and HIV, as confirmed by serology. Syphilis serology testing was also positive. A Girdlestone's procedure was performed and samples were collected for routine cultures for bacteria and acid fast bacilli, all resulting negative.Although histological findings were inconclusive, confirmed positive serology for syphilis associated with progressive arthropathy was strongly suggestive of tertiary syphilis, probably exacerbated by HIV-HCV co-infection. The patient partially recovered the ability to walk. CONCLUSIONS: Due to the resurgence of syphilis, this disease should be considered as a possible cause of neuropathic arthropathy when other infectious causes have been ruled out, particularly in patients with HIV and/or HCV co-infection

Examining intergenerational risk factors for conduct problems using polygenic scores in the Norwegian Mother, Father and Child Cohort Study

The aetiology of conduct problems involves a combination of genetic and environmental factors, many of which are inherently linked to parental characteristics given parents' central role in children's lives across development. It is important to disentangle to what extent links between parental heritable characteristics and children's behaviour are due to transmission of genetic risk or due to parental indirect genetic influences via the environment (i.e., genetic nurture). We used 31,290 genotyped mother-father-child trios from the Norwegian Mother, Father and Child Cohort Study (MoBa), testing genetic transmission and genetic nurture effects on conduct problems using 13 polygenic scores (PGS) spanning psychiatric conditions, substance use, education-related factors, and other risk factors. Maternal or self-reports of conduct problems at ages 8 and 14 years were available for up to 15,477 children. We found significant genetic transmission effects on conduct problems for 12 out of 13 PGS at age 8 years (strongest association: PGS for smoking, β = 0.07, 95% confidence interval = [0.05, 0.08]) and for 4 out of 13 PGS at age 14 years (strongest association: PGS for externalising problems, β = 0.08, 95% confidence interval = [0.05, 0.11]). Conversely, we did not find genetic nurture effects for conduct problems using our selection of PGS. Our findings provide evidence for genetic transmission in the association between parental characteristics and child conduct problems. Our results may also indicate that genetic nurture via traits indexed by our polygenic scores is of limited aetiological importance for conduct problems-though effects of small magnitude or effects via parental traits not captured by the included PGS remain a possibility

Language and learning science in South Africa

South Africa is a multilingual country with 11 official languages. However, English dominates as the language of access and power and although the Language-in- Education Policy (1997) recommends school language policies that will promote additive bilingualism and the use of learners' home languages as languages of learning and teaching, there has been little implementation of these recommendations by schools. This is despite the fact that the majority of learners do not have the necessary English language proficiency to successfully engage with the curriculum and that teachers frequently are obliged to resort to using the learners' home language to mediate understanding. This research investigates the classroom language practices of six Grade 8 science teachers, teaching science through the medium of English where they and their learners share a common home language, Xhosa. Teachers' lessons were videotaped, transcribed and analysed for the opportunities they offered learners for language development and conceptual challenge. The purpose of the research is to better understand the teachers' perceptions and problems and to be able to draw on examples of good practice, to inform teacher training and to develop a coherent bilingual approach for teaching science through the medium of English as an additional language

Identity exploration and development in TESOL teacher education: A three-dimensional space narrative inquiry perspective

This study explores the professional identity development of five non-native English-speaking teacher learners from different backgrounds who were studying for a Master’s degree in Applied Linguistics/TESOL at an Australian university, following the three-dimensional space narrative inquiry framework (Clandinin & Connelly, 2000). The study aims to address how identity work could be utilized in teacher education to enrich teacher learners’ learning experience and prepare them for better developing their teacher selves. Participants attended two one-hour story-telling sessions aimed to elicit various aspects of their experience within the teacher education program such as native/non-native issues, transition in time and space and changes in expectations, and the learning environment. Their stories, structured and analyzed following the three-dimensional space narrative inquiry framework (Interaction, Continuity, and Situation) revealed their growth, satisfaction, and tensions resulting from becoming part of the community of practice in the Australian teacher education program. This research highlights the role of conducting identity exploration interventions within the context of teacher education in assisting TESOL teachers to construct and reconstruct their professional identity. It also suggests classroom activities designed based on the three-dimensional space narrative inquiry framework to make identity work a crucial part of teacher development within teacher education courses

Role of Sleep Disturbance in Chronic Hepatitis C Infection

Chronic infection with the hepatitis C virus (CHC) is associated with physical and mental symptoms including fatigue and depression that adversely affect quality of life. A related complaint, sleep disturbance, has received little attention in the literature, with the exception of sleep changes noted in cirrhosis and end-stage liver disease. We present an overview of studies indicating sleep problems in patients with CHC, with about 60% to 65% of individuals reporting such complaints. Evidence suggests that impairments in sleep quality exist independent of antiviral therapy with interferon-α and prior to advanced stages of liver disease. Further investigation of sleep disturbance in CHC patients with a mild stage of liver disease may provide important information on disease course as well as allow additional opportunities for patient support