The sequences of 150,119 genomes in the UK Biobank

Detailed knowledge of how diversity in the sequence of the human genome affects phenotypic diversity depends on a comprehensive and reliable characterization of both sequences and phenotypic variation. Over the past decade, insights into this relationship have been obtained from whole-exome sequencing or whole-genome sequencing of large cohorts with rich phenotypic data(1,2). Here we describe the analysis of whole-genome sequencing of 150,119 individuals from the UK Biobank(3). This constitutes a set of high-quality variants, including 585,040,410 single-nucleotide polymorphisms, representing 7.0% of all possible human single-nucleotide polymorphisms, and 58,707,036 indels. This large set of variants allows us to characterize selection based on sequence variation within a population through a depletion rank score of windows along the genome. Depletion rank analysis shows that coding exons represent a small fraction of regions in the genome subject to strong sequence conservation. We define three cohorts within the UK Biobank: a large British Irish cohort, a smaller African cohort and a South Asian cohort. A haplotype reference panel is provided that allows reliable imputation of most variants carried by three or more sequenced individuals. We identified 895,055 structural variants and 2,536,688 microsatellites, groups of variants typically excluded from large-scale whole-genome sequencing studies. Using this formidable new resource, we provide several examples of trait associations for rare variants with large effects not found previously through studies based on whole-exome sequencing and/or imputation

MiR-126 and miR-126* regulate shear-resistant firm leukocyte adhesion to human brain endothelium

Leukocyte adhesion to brain endothelial cells, the blood-brain barrier main component, is a critical step in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). Leukocyte adhesion is mediated mainly by selectins, cell adhesion molecules and chemokines induced by pro-inflammatory cytokines such as TNFα and IFNγ, but the regulation of this process is not fully clear. This study investigated the regulation of firm leukocyte adhesion to human brain endothelium by two different brain endothelial microRNAs (miRs), miR-126 and miR-126*, that are downregulated by TNFα and IFNγ in a human brain endothelial cell line, hCMEC/D3. Using a leukocyte adhesion in vitro assay under shear forces mimicking blood flow, we observed that reduction of endothelial miR-126 and miR-126* enhanced firm monocyte and T cell adhesion to hCMEC/D3 cells, whereas their increased expression partially prevented THP1, Jurkat and primary MS patient-derived PBMC firm adhesion. Furthermore, we observed that miR-126* and miR-126 downregulation increased E-selectin and VCAM1, respectively, while miR-126 overexpression reduced VCAM1 and CCL2 expression by hCMEC/D3 cells, suggesting that these miRs regulate leukocyte adhesion by modulating the expression of adhesion-associated endothelial mRNA targets. Hence, human brain endothelial miR-126 and miR-126* could be used as a therapeutic tool to reduce leukocyte adhesion and thus reduce neuroinflammation

Identification of three differentially expressed hydrophobins in Pleurotus ostreatus (oyster mushroom)

Three proteins with characteristic features of class I hydrophobins, designated POH1, POH2 and POH3, were isolated from the basidiomycete Pleurotus ostreatus. Based on N-terminal sequence analyses, their cDNAs were isolated using RT-PCR; the cDNAs and corresponding genes were sequenced and their regulation studied. POH1 is expressed in the fruiting bodies but not in vegetative mycelium. The regulation of POH2 and POH3 is tightly correlated. Both genes are switched off in the fruiting bodies but abundantly expressed in the vegetative mycelium of both monokaryon and dikaryon. POH2 and POH3 were isolated from the culture medium and from aerial hyphae. Co-purified POH2 and POH3 assembled in vitro into a protein membrane with a typical rodlet pattern as found previously with other hydrophobins. Similar structures were detected on the surface of aerial hyphae

Physical activity buffers the effects of family conflict on depressed mood: a study on adolescent girls and boys.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.This paper investigates the relationship between physical activity and depressed mood, under conditions of family conflict. We analyze data from a representative sample of 7,232 Icelandic adolescents. Analysis of variance was carried out to test for main and interaction effects. The study shows that while family conflict increases the likelihood of depressed mood, among adolescents, physical activity decreases the likelihood of depressed mood. Furthermore, physical activity plays a more important role among those adolescents living in aversive circumstances, than other adolescents, as family conflict and physical activity interact in the effect on depressed mood for adolescents living in such circumstances. The findings highlight the role of physical activity in decreasing mental distress among adolescents, especially those living in aversive circumstances at home

A model of sexual abuse's effects on suicidal behavior and delinquency: The role of emotions as mediating factors

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldDrawing on Agnew’s general strain theory, we examined whether depressed mood and anger mediated the effects of sexual abuse on suicidal behavior and delinquency. Participants included 9,113 students attending high schools in Iceland. Structural equation modeling showed that, while controlling for family structure and parental education, being exposed to strain in the form of sexual abuse was positively related to both depressed mood and anger. The effects of sexual abuse on suicidal behavior of both boys and girls were twice as strong through depressed mood as through anger. The effects of sexual abuse on outwardly-directed forms of delinquency for both genders were stronger through anger than through depressed mood. These findings highlight the complex nature of the effects of strain on adolescents’ emotions and behavior. Moreover, they show that depression—in contrast to outwardly-directed delinquency, where feelings of anger are predominantly influential—is more relevant than anger to suicidal behavior

False confessions and individual differences: The importance of victimization among youth

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThe principal aim of the study was to investigate the relationship between false confession during custodial interrogation and history of victimization among young persons. The participants were 10,363 students in further education in Iceland (mean age 17.6-years, range 15-24). The participants completed questionnaires relating to mental health, self-esteem, victimization, delinquency, peer delinquency, drug use, attitudes towards school, and parental support. They also reported the extent of their police involvement and if they had ever falsely confessed to police. Almost one-fifth (19.8%) of the total sample stated that they had been interrogated by the police in relation to a suspected offence, of those interrogated 8.8% (1.7% of the total sample) claimed to have made false confessions to the police. Over one-third (37.1%) reported being wrongfully convicted for the false confession offence. The main motives were to protect a peer and avoid police pressure. A stepwise discriminant function analysis showed that three variables (bullying victimization, negative attitudes towards school, and delinquency) discriminated significantly between the two groups after taking into account the relationship between the psychological scales. The findings provide strong evidence of the relationship between being a victim of bullying and giving false confessions

Trends in depressive symptoms, anxiety symptoms and visits to healthcare specialists: A national study among Icelandic adolescents.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldAIMS: The aim of the study was to examine trends in adolescent depression and anxiety symptoms from 1997 to 2006, using four time-points (1997, 2000, 2003, and 2006), and adolescent mental health service use in the same period, using three time-points (1997, 2000, and 2006). METHODS: Four cross-sectional population-based samples of 14- and 15-year-old students, attending the compulsory 9th and 10th grades of the Icelandic secondary school system, completed questionnaires relating to mental health. In total, 21,245 students participated in the four studies. RESULTS: Anxiety symptoms increased significantly for both boys and girls, throughout the period from 1997 to 2006. Depressive symptoms increased significantly for girls, while there were no significant changes in depression among boys. During the same time period, the proportion of adolescents who visited healthcare specialists, i.e. psychiatrists, psychologists and social workers, increased significantly. The results revealed that regular visits (six times or more during 1 year) to psychiatrists and psychologists increased significantly over the same period among girls but not among boys. CONCLUSIONS: The findings show that symptoms of depression and anxiety have increased among adolescents in Iceland. Future work would benefit from further research into the trends in risk and protective factors associated with these outcomes. The findings call particular attention to the increasing risk for depression and anxiety symptoms among girls