Genetic and Inflammatory Biomarkers Classify Small Intestine Inflammation in Asymptomatic First-degree Relatives of Patients With Crohn's Disease

BACKGROUND &amp; AIMS: Relatives of individuals with Crohn's disease (CD) carry CD-associated genetic variants and are often exposed to environmental factors that increase their risk for this disease. We aimed to estimate the utility of genotype, smoking status, family history, and other biomarkers can be used to calculate risk in asymptomatic first-degree relatives of patients with CD.METHODS: We recruited 480 healthy first-degree relatives (full siblings, offspring or parents) of patients with CD through the Guy's and St Thomas' NHS Foundation Trust and from members of Crohn's and Colitis, United Kingdom. DNA samples were genotyped using the Immunochip. We calculated a risk score for 454 participants, based on 72 genetic variants associated with CD, family history, and smoking history. Participants were assigned to highest and lowest risk score quartiles. We assessed pre-symptomatic inflammation by capsule endoscopy and measured 22 markers of inflammation in stool and serum samples (reference standard). Two machine-learning classifiers (elastic net and random forest) were used to assess the ability of the risk factors and biomarkers to identify participants with small intestinal inflammation in the same dataset.RESULTS: The machine-learning classifiers identified participants with pre-symptomatic intestinal inflammation: elastic net (area under the curve, 0.80; 95% CI, 0.62-0.98) and random forest (area under the curve, 0.87; 95% CI, 0.75-1.00). The elastic net method identified 3 variables that can be used to calculate odds for intestinal inflammation: combined family history of CD (odds ratio, 1.31), genetic risk score (odds ratio, 1.14), and fecal level of calprotectin (odds ratio, 1.04). These same 3 variables were among the 5 factors associated with intestinal inflammation in the random forest model.CONCLUSION: Using machine learning classifiers, we found that genetic variants associated with CD, family history, and fecal level of calprotectin together identify individuals with pre-symptomatic intestinal inflammation who are therefore at risk for CD. A tool for detecting people at risk for CD before they develop symptoms would help identify the individuals most likely to benefit from early intervention.</p

The correlation between reading and mathematics ability at age twelve has a substantial genetic component

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children’s ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child’s cognitive abilities at age twelve

Characterization and structure of hypomania in a British nonclinical adolescent sample

BACKGROUND: This study aimed to test the validity of using the Hypomania Checklist-16 [HCL-16] to measure hypomania in a British adolescent community sample. Limited research is available concerning the characterization of hypomania among community adolescent samples, particularly in the UK, despite its potential importance for early intervention policy development. METHOD: To explore the structure and characterization of hypomania in a British adolescent nonclinical cohort, over 1400 17 year olds (Mean=17.05 years; SD=0.88) completed the HCL-16 along with measures of different psychological and psychopathological dimensions. RESULTS: Principal components analysis revealed a 2-component solution for the HCL-16, described as active-elated and irritable/risk-taking. Hypomanic symptoms were significantly correlated with many psychopathological dimensions. There were distinct correlation patterns for the two HCL-16 subscales, with the irritability/risk-taking subscale showing significantly stronger associations with psychotic-like experiences, internalizing and externalizing problems, and reduced life satisfaction relative to the active-elated dimension. Adolescents at ‘high-risk’ for bipolar disorder reported more psychopathology relative to the comparison group. LIMITATIONS: Absence of the clinical diagnosis of bipolar disorder in the sample means that the classification of the ‘high-risk’ group cannot be confirmed. CONCLUSIONS: The structure of the HCL-16 in this UK adolescent sample mirrored that observed in adult and clinical cohorts. The observed links between the HCL-16 and psychopathological dimensions that have been previously associated with both hypomania and bipolar disorder lend support to the HCL-16's validity as a hypomania instrument for adolescents. Better understanding of hypomania prior to adulthood has considerable potential for informing early intervention approaches

Positioning discourse on homophobia in schools: what have lesbian and gay families got to say?

This paper reports findings from a study in England, which investigated the experiences of lesbian and gay parents in relation to homophobia in primary and secondary schools. The study was part of a larger European Union project investigating the impact of family and school alliances against homophobic and transphobic bullying in schools across six nation states. Qualitative in-depth semi-structured interviews with seven lesbian and gay parents from five families were conducted to explore their unique experience and perspectives on these issues. Discourse analysis was used to facilitate understanding of how lesbian and gay families negotiated the outsider/insider and public/private spheres of the school and communities of which they were a part. Parents identified a number of strategies to address their experiences of homophobia within schools. The findings have implications for how social work recognises and promotes diversity and equality when working with lesbian, gay, bisexual and transgender families, as social workers have a powerful role in supporting families. This involves recognising the strengths of lesbian, gay, bisexual and transgender families in their assessments

Positioning discourse on homophobia in schools: What have lesbian and gay families got to say?

This paper reports findings from a study in England, which investigated the experiences of lesbian and gay parents in relation to homophobia in primary and secondary schools. The study was part of a larger European Union project investigating the impact of family and school alliances against homophobic and transphobic bullying in schools across six nation states. Qualitative in-depth semi-structured interviews with seven lesbian and gay parents from five families were conducted to explore their unique experience and perspectives on these issues. Discourse analysis was used to facilitate understanding of how lesbian and gay families negotiated the outsider/insider and public/private spheres of the school and communities of which they were a part. Parents identified a number of strategies to address their experiences of homophobia within schools. The findings have implications for how social work recognises and promotes diversity and equality when working with lesbian, gay, bisexual and transgender families, as social workers have a powerful role in supporting families. This involves recognising the strengths of lesbian, gay, bisexual and transgender families in their assessments

Unsettling lesbian motherhood: Critical reflections over a generation (1990-2015)

This article explores how advancements in equality rights combine with attitudinal changes in UK society and LGBTQ communities to impact on the experience of lesbian mothers over a generation. The author reflects on ordinary moments where sexuality and relationships become meaningful and situate emotions at the heart of analytical enquiry because it is through emotional interactions that micro–macro networks of relations intersect. Autobiography is combined with original data from empirical research to provide analytical entry points, which aims to advance understanding and also facilitate reflection on how we understand and come to know queer parenthood. Whilst there are now many routes into lesbian motherhood and the stigma of queer kinship is diminishing, this article demonstrates the need to problematize the prevailing narratives of coupledom that are emerging and tease apart the conflation of temporal progression, progressive rights and narratives of progress

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe