Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci.

Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10(-6)) and rs8057927 in CDH13 (P=1.39 × 10(-5)). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10(-7)). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10(-7)). This signal was replicated in the follow-up analysis (P=2.3 × 10(-2)). Significant interaction with maternal CMV infection was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies

Heritability of DNA-damage-induced apoptosis and its relationship with age in lymphocytes from female twins

Apoptosis is a physiological form of cell death important in normal processes such as morphogenesis and the functioning of the immune system. In addition, defects in the apoptotic process play a major role in a number of important areas of disease, such as autoimmune diseases and cancer. DNA-damage-induced apoptosis plays a vital role in the maintenance of genomic stability by the removal of damaged cells. Previous studies of the apoptotic response (AR) to radiation-induced DNA damage of lymphoid cells from individuals carrying germline TP53 mutations have demonstrated a defective AR compared with normal controls. We have also previously demonstrated that AR is reduced as individuals age. Results from the current study on 108 twins aged 18–80 years confirm these earlier findings that the AR of lymphoid cells to DNA damage is significantly reduced with increasing age. In addition this twin study shows, for the first time, that DNA-damage-induced AR has a strong degree of heritability of 81% (95% confidence interval 67–89%). The vital role of DNA-damage-induced apoptosis in maintaining genetic stability, its relationship with age and its strong heritability underline the importance of this area of biology and suggest areas for further study

Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data

This study was supported by a grant from the National Institute for Health Research (NIHR) under its Health Technology Assessment programme (reference No 13/03/25, to ARM

Results of a participatory needs assessment demonstrate an opportunity to involve people who use alcohol in drug user activism and harm reduction

BACKGROUND: Drug users’ organizations have made progress in recent years in advocating for the health and human rights of people who use illicit drugs but have historically not emphasized the needs of people who drink alcohol. METHODS: This paper reports on a qualitative participatory needs assessment with people who use illicit substances in British Columbia, Canada. We held workshops in 17 communities; these were facilitated by people who use illicit drugs, recorded with ethnographic fieldnotes, and analyzed using critical theory. RESULTS: Although the workshops were targeted to people who use illicit drugs, people who primarily consume alcohol also attended. An unexpected finding was the potential for drug users’ organizations and other harm reduction programs to involve “illicit drinkers”: people who drink non-beverage alcohol (e.g. mouthwash, rubbing alcohol) and those who drink beverage alcohol in criminalized ways (e.g., homeless drinkers). Potential points of alliance between these groups are common priorities (specifically, improving treatment by health professionals and the police, expanding housing options, and implementing harm reduction services), common values (reducing surveillance and improving accountability of services), and polysubstance use. CONCLUSIONS: Despite these potential points of alliance, there has historically been limited involvement of illicit drinkers in drug users’ activism. Possible barriers to involvement of illicit drinkers in drug users’ organizations include racism (as discourses around alcohol use are highly racialized), horizontal violence, the extreme marginalization of illicit drinkers, and knowledge gaps around harm reduction for alcohol. Understanding the commonalities between people who use drugs and people who use alcohol, as well as the potential barriers to alliance between them, may facilitate the greater involvement of illicit drinkers in drug users’ organizations and harm reduction services

A genome for gnetophytes and early evolution of seed plants

Genome sequencing, assembly and annotation were conducted by the Novogene Bioinformatics Institute, Beijing, China; mutual contracts were No. NHT140016 and NVT140016004. This work was supported by funding from the Scientific Project of Shenzhen Urban Administration (201519) and a Major Technical Research Project of the Innovation of Science and Technology Commission of Shenzhen (JSGG20140515164852417). Additional funding was provided in particular by the Scientific Research Program of Sino-Africa Joint Research Center (SAJL201607). We thank X.Q. Wang, G.W. Hu, Z.D. Chen and Y.H. Guo for comments on gnetophyte phylogenetic relationships and ecological issues; H. Wu and X.P. Ning for discussion of related organ development; K.K. Wan and S. Sun for additional help on the analysis of repeats. We also thank X.Y. for support of funding coordination. Y.V.d.P. acknowledges the Multidisciplinary Research Partnership ‘Bioinformatics: from nucleotides to networks’ Project (no. 01MR0310W) of Ghent University, and funding from the European Union Seventh Framework Programme (FP7/2007-2013) under European Research Council Advanced Grant Agreement 322739-DOUBLEUP

Individual Differences in Processing Speed and Working Memory Speed as Assessed with the Sternberg Memory Scanning Task

The Sternberg Memory Scanning (SMS) task provides a measure of processing speed (PS) and working memory retrieval speed (WMS). In this task, participants are presented with sets of stimuli that vary in size. After a delay, one item is presented, and participants indicate whether or not the item was part of the set. Performance is assessed by speed and accuracy for both the positive (item is part of the set) and the negative trials (items is not part of the set). To examine the causes of variation in PS and WMS, 623 adult twins and their siblings completed the SMS task. A non-linear growth curve (nLGC) model best described the increase in reaction time with increasing set size. Genetic analyses showed that WMS (modeled as the Slope in the nLGC model) has a relatively small variance which is not due to genetic variation while PS (modeled as the Intercept in the nLGC model) showed large individual differences, part of which could be attributed to additive genetic factors. Heritability was 38% for positive and 32% for negative trials. Additional multivariate analyses showed that the genetic effects on PS for positive and negative trials were completely shared. We conclude that genetic influences on working memory performance are more likely to act upon basic processing speed and (pre)motoric processes than on the speed with which an item is retrieved from short term memory

Added Value Measures in Education Show Genetic as Well as Environmental Influence

Does achievement independent of ability or previous attainment provide a purer measure of the added value of school? In a study of 4000 pairs of 12-year-old twins in the UK, we measured achievement with year-long teacher assessments as well as tests. Raw achievement shows moderate heritability (about 50%) and modest shared environmental influences (25%). Unexpectedly, we show that for indices of the added value of school, genetic influences remain moderate (around 50%), and the shared (school) environment is less important (about 12%). The pervasiveness of genetic influence in how and how much children learn is compatible with an active view of learning in which children create their own educational experiences in part on the basis of their genetic propensities

Genetic and Environmental Influences on Female Sexual Orientation, Childhood Gender Typicality and Adult Gender Identity

Background: Human sexual orientation is influenced by genetic and non-shared environmental factors as are two important psychological correlates – childhood gender typicality (CGT) and adult gender identity (AGI). However, researchers have been unable to resolve the genetic and non-genetic components that contribute to the covariation between these traits, particularly in women. Methodology/Principal Findings: Here we performed a multivariate genetic analysis in a large sample of British female twins (N = 4,426) who completed a questionnaire assessing sexual attraction, CGT and AGI. Univariate genetic models indicated modest genetic influences on sexual attraction (25%), AGI (11%) and CGT (31%). For the multivariate analyses, a common pathway model best fitted the data. Conclusions/Significance: This indicated that a single latent variable influenced by a genetic component and common nonshared environmental component explained the association between the three traits but there was substantial measurement error. These findings highlight common developmental factors affecting differences in sexual orientation

On the sources of the height–intelligence correlation: New insights from a bivariate ACE model with assortative mating

A robust positive correlation between height and intelligence, as measured by IQ tests, has been established in the literature. This paper makes several contributions toward establishing the causes of this association. First, we extend the standard bivariate ACE model to account for assortative mating. The more general theoretical framework provides several key insights, including formulas to decompose a cross-trait genetic correlation into components attributable to assortative mating and pleiotropy and to decompose a cross-trait within-family correlation. Second, we use a large dataset of male twins drawn from Swedish conscription records and examine how well genetic and environmental factors explain the association between (i) height and intelligence and (ii) height and military aptitude, a professional psychogologist’s assessment of a conscript’s ability to deal with wartime stress. For both traits, we find suggestive evidence of a shared genetic architecture with height, but we demonstrate that point estimates are very sensitive to assumed degrees of assortative mating. Third, we report a significant within-family correlation between height and intelligence \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$(\hat{\rho}=0.10),$$\end{document} suggesting that pleiotropy might be at play

Violence and post-traumatic stress disorder in Sao Paulo and Rio de Janeiro, Brazil: the protocol for an epidemiological and genetic survey

Background: violence is a public health major concern, and it is associated with post-traumatic stress disorder and other psychiatric outcomes. Brazil is one of the most violent countries in the world, and has an extreme social inequality. Research on the association between violence and mental health may support public health policy and thus reduce the burden of disease attributable to violence. the main objectives of this project were: to study the association between violence and mental disorders in the Brazilian population; to estimate the prevalence rates of exposure to violence, post-traumatic stress disorder, common metal disorder, and alcohol hazardous use and dependence: and to identify contextual and individual factors, including genetic factors, associated with the outcomes.Methods/design: one phase cross-sectional survey carried out in São Paulo and Rio de Janeiro, Brazil. A multistage probability to size sampling scheme was performed in order to select the participants (3000 and 1500 respectively). the cities were stratified according to homicide rates, and in São Paulo the three most violent strata were oversampled. the measurements included exposure to traumatic events, psychiatric diagnoses (CIDI 2.1), contextual (homicide rates and social indicators), and individual factors, such as demographics, social capital, resilience, help seeking behaviours. the interviews were carried between June/2007 February/2008, by a team of lay interviewers. the statistical analyses will be weight-adjusted in order to take account of the design effects. Standardization will be used in order to compare the results between the two centres. Whole genome association analysis will be performed on the 1 million SNP (single nucleotide polymorphism) arrays, and additional association analysis will be performed on additional phenotypes. the Ethical Committee of the Federal University of São Paulo approved the study, and participants who matched diagnostic criteria have been offered a referral to outpatient clinics at the Federal University of São Paulo and Federal University of Rio de Janeiro