Genetic and environmental influences on alcohol consumption in middle to late life.

Objective: Alcohol use is common in older adults and linked to poor health and aging outcomes. Studies have demonstrated genetic and environmental contributions to the quantity of alcohol consumption in mid-to-late life, but less is known about whether these influences are moderated by sociodemographic factors such as age, sex, and educational attainment. This study sought to better understand sociodemographic trends in alcohol consumption across the second half of the life course and their underlying genetic and environmental influences.

Genome-wide meta-analyses of non-response to antidepressants identify novel loci and potential drugs.

Antidepressants exhibit a considerable variation in efficacy, and increasing evidence suggests that individual genetics contribute to antidepressant treatment response. Here, we combined data on antidepressant non-response measured using rating scales for depressive symptoms, questionnaires of treatment effect, and data from electronic health records, to increase statistical power to detect genomic loci associated with non-response to antidepressants in a total sample of 135,471 individuals prescribed antidepressants (25,255 non-responders and 110,216 responders). We performed genome-wide association meta-analyses, genetic correlation analyses, leave-one-out polygenic prediction, and bioinformatics analyses for genetically informed drug prioritization.

Target cell tension regulates macrophage trogocytosis.

Macrophages are known to engulf small membrane fragments, or trogocytose, target cells and pathogens, rather than fully phagocytose them. However, little is known about what causes macrophages to choose trogocytosis versus phagocytosis. Here, we report that cortical tension of target cells is a key regulator of macrophage trogocytosis.

Polygenic risk scores and help-seeking behaviour in young people with recent onset of mood and psychotic disorders.

Objectives: We examined associations between polygenic risk scores (PRS) for depression (PRS-MDD), psychosis (PRS-SCZ), bipolar disorders (PRS-BD) and neuroticism (PRS-NEU) and (i) help-seeking, and (ii) new onset cases of full-threshold mood or psychotic disorders in youth.

Methods: Help-seeking for mental health problems was assessed by self-report and mood and psychotic disorders were identified using the Composite International Diagnostic Interview. A principal component analysis of the four selected PRS identified two dimensions (BD-SCZ; MDD-NEU) that accounted for 69.

Parkinson's Disease Polygenic Risk Score and Neurological Involvement in Carriers of the FMR1 Premutation Allele: A Case for Genetic Modifier.

Background: Premutation alleles of the FMR1 X-linked gene containing CGG repeat expansions ranging from 55 to 200 are associated with diverse late-onset neurological involvements, including most severe disorder termed Fragile X-associated Tremor/Ataxia Syndrome (FXTAS). It is intriguing that at least one-third of male, and a much lower than predicted from the X-linkage proportion of female carriers are free of this syndrome. This suggests the existence of secondary genetic factors modifying the risk of neurological involvements in these carriers.

The effect of polygenic liability to mental disorders on COVID-19 outcomes in people with depression: the mediating role of anxiety.

Background: Genetic vulnerability to mental disorders has been associated with coronavirus disease-19 (COVID-19) outcomes. We explored whether polygenic risk scores (PRSs) for several mental disorders predicted poorer clinical and psychological COVID-19 outcomes in people with pre-existing depression.

Methods: Data from three assessments of the Australian Genetics of Depression Study ( = 4405; 52.

Anorexia nervosa polygenic risk, beyond diagnoses: relationship with adolescent disordered eating and behaviors in an Australian female twin population.

Background: It is well established that there is a substantial genetic component to eating disorders (EDs). Polygenic risk scores (PRSs) can be used to quantify cumulative genetic risk for a trait at an individual level. Recent studies suggest PRSs for anorexia nervosa (AN) may also predict risk for other disordered eating behaviors, but no study has examined if PRS for AN can predict disordered eating as a global continuous measure.

Markers of positive affect and brain state synchrony discriminate melancholic from non-melancholic depression using naturalistic stimuli.

Melancholia has been proposed as a qualitatively distinct depressive subtype associated with a characteristic symptom profile (psychomotor retardation, profound anhedonia) and a better response to biological therapies. Existing work has suggested that individuals with melancholia are blunted in their display of positive emotions and differ in their neural response to emotionally evocative stimuli. Here, we unify these brain and behavioural findings amongst a carefully phenotyped group of seventy depressed participants, drawn from an established Australian database (the Australian Genetics of Depression Study) and further enriched for melancholia (high ratings of psychomotor retardation and anhedonia).

Exploring the Germline Genetics of In Situ and Invasive Cutaneous Melanoma: A Genome-Wide Association Study Meta-Analysis.

Importance: It is unknown whether germline genetic factors influence in situ melanoma risk differently than invasive melanoma risk.

Objective: To determine whether differences in risk of in situ melanoma and invasive melanoma are heritable.

Design, Setting, And Participants: Three genome-wide association study meta-analyses were conducted of in situ melanoma vs controls, invasive melanoma vs controls, and in situ vs invasive melanoma (case-case) using 4 population-based genetic cohorts: the UK Biobank, the FinnGen cohort, the QSkin Sun and Health Study, and the Queensland Study of Melanoma: Environmental and Genetic Associations (Q-MEGA).

Therapeutic efficacy of pyronaridine-artesunate (Pyramax) in treating malaria in the central highlands of Vietnam.

Unlabelled: The emergence and spread of chloroquine-resistant have necessitated the assessment of alternative blood schizonticidal drugs. In Vietnam, chloroquine-resistant malaria has been reported. In an open-label, single-arm trial, the safety, tolerability, and efficacy of pyronaridine-artesunate (Pyramax, PA) was evaluated in Dak Nong province, Vietnam.

Genetic neurodevelopmental clustering and dyslexia.

Dyslexia is a learning difficulty with neurodevelopmental origins, manifesting as reduced accuracy and speed in reading and spelling. It is substantially heritable and frequently co-occurs with other neurodevelopmental conditions, particularly attention deficit-hyperactivity disorder (ADHD). Here, we investigate the genetic structure underlying dyslexia and a range of psychiatric traits using results from genome-wide association studies of dyslexia, ADHD, autism, anorexia nervosa, anxiety, bipolar disorder, major depressive disorder, obsessive compulsive disorder, schizophrenia, and Tourette syndrome.

Differential etiologic associations of heroin use and prescription opioid misuse with psychopathology.

Patterns of association with externalizing and internalizing features differ across heroin use and prescription opioid misuse (POM). The present study examined whether heroin use and POM display differential etiologic overlap with symptoms of conduct disorder (CD), adult antisocial behavior (AAB), and major depressive episodes (MDEs), how aggregating heroin use and POM into a single phenotype may bias results, and explored potential sex differences. Seven thousand one hundred and sixty-four individual twins from the Australian Twin Registry (ATR; 59.

Comprehensive Sex-Stratified Genetic Analysis of 28 Blood Biomarkers and Depression Reveals a Significant Association between Depression and Low Levels of Total Protein in Females.

Introduction: Major depression (MD) is more common amongst women than men, and MD episodes have been associated with fluctuations in reproductive hormones amongst women. To investigate biological underpinnings of heterogeneity in MD, the associations between depression, stratified by sex and including perinatal depression (PND), and blood biomarkers, using UK Biobank (UKB) data, were evaluated, and extended to include the association of depression with biomarker polygenic scores (PGS), generated as proxy for each biomarker.

Method: Using female ( = 39,761) and male ( = 38,821) UKB participants, lifetime MD and PND were tested for association with 28 blood biomarkers.