Association Study of 167 Candidate Genes for Schizophrenia Selected by a Multi-Domain Evidence-Based Prioritization Algorithm and Neurodevelopmental Hypothesis

Integrating evidence from multiple domains is useful in prioritizing disease candidate genes for subsequent testing. We ranked all known human genes (n = 3819) under linkage peaks in the Irish Study of High-Density Schizophrenia Families using three different evidence domains: 1) a meta-analysis of microarray gene expression results using the Stanley Brain collection, 2) a schizophrenia protein-protein interaction network, and 3) a systematic literature search. Each gene was assigned a domain-specific p-value and ranked after evaluating the evidence within each domain. For comparison to this ranking process, a large-scale candidate gene hypothesis was also tested by including genes with Gene Ontology terms related to neurodevelopment. Subsequently, genotypes of 3725 SNPs in 167 genes from a custom Illumina iSelect array were used to evaluate the top ranked vs. hypothesis selected genes. Seventy-three genes were both highly ranked and involved in neurodevelopment (category 1) while 42 and 52 genes were exclusive to neurodevelopment (category 2) or highly ranked (category 3), respectively. The most significant associations were observed in genes PRKG1, PRKCE, and CNTN4 but no individual SNPs were significant after correction for multiple testing. Comparison of the approaches showed an excess of significant tests using the hypothesis-driven neurodevelopment category. Random selection of similar sized genes from two independent genome-wide association studies (GWAS) of schizophrenia showed the excess was unlikely by chance. In a further meta-analysis of three GWAS datasets, four candidate SNPs reached nominal significance. Although gene ranking using integrated sources of prior information did not enrich for significant results in the current experiment, gene selection using an a priori hypothesis (neurodevelopment) was superior to random selection. As such, further development of gene ranking strategies using more carefully selected sources of information is warranted.     

Tuberculosis in Antiretroviral Treatment Programs in Lower Income Countries: Availability and Use of Diagnostics and Screening

Objectives

In resource-constrained settings, tuberculosis (TB) is a common opportunistic infection and cause of death in HIV-infected persons. TB may be present at the start of antiretroviral therapy (ART), but it is often under-diagnosed. We describe approaches to TB diagnosis and screening of TB in ART programs in low- and middle-income countries.

Methods and findings

We surveyed ART programs treating HIV-infected adults in sub-Saharan Africa, Asia and Latin America in 2012 using online questionnaires to collect program-level and patient-level data. Forty-seven sites from 26 countries participated. Patient-level data were collected on 987 adult TB patients from 40 sites (median age 34.7 years; 54% female). Sputum smear microscopy and chest radiograph were available in 47 (100%) sites, TB culture in 44 (94%), and Xpert MTB/RIF in 23 (49%). Xpert MTB/RIF was rarely available in Central Africa and South America. In sites with access to these diagnostics, microscopy was used in 745 (76%) patients diagnosed with TB, culture in 220 (24%), and chest X-ray in 688 (70%) patients. When free of charge culture was done in 27% of patients, compared to 21% when there was a fee (p = 0.033). Corresponding percentages for Xpert MTB/RIF were 26% and 15% of patients (p = 0.001). Screening practices for active disease before starting ART included symptom screening (46 sites, 98%), chest X-ray (38, 81%), sputum microscopy (37, 79%), culture (16, 34%), and Xpert MTB/RIF (5, 11%).

Conclusions

Mycobacterial culture was infrequently used despite its availability at most sites, while Xpert MTB/RIF was not generally available. Use of available diagnostics was higher when offered free of charge.     

No Association between Antenatal Common Mental Disorders in Low-Obstetric Risk Women and Adverse Birth Outcomes in Their Offspring: Results from the CDS Study in Ghana and C?te D'Ivoire

Background

Evidence linking common mental disorders (CMD) in pregnant women to adverse birth outcomes is inconsistent, and studies often failed to control for pregnancy complications. This study aimed to explore the association between antenatal depression and anxiety symptoms and birth outcomes in a low-obstetric risk sample of mother/child dyads in Ghana and Côte d’Ivoire.

Methods

In 2010-2011, a prospective cohort of 1030 women in their third trimester in Ghana and Côte d’Ivoire was enrolled. Depression and anxiety were assessed in the third trimester using the Patient Health Questionnaire depression module and the 7-item Generalized Anxiety Disorder scale. 719 mother/child dyads were included in the analysis. We constructed multivariate regression models to estimate the association between CMD and low birth weight (LBW), and preterm birth (PTB) to control for potential confounders.

Results

The prevalence of depression and anxiety symptoms were 28.9% and 14.2% respectively. The mean birth weight was 3172.1g (SD 440.6) and the prevalence of LBW was 1.7%. The mean gestational age was 39.6 weeks and the proportion of PTB was 4%. Multivariate linear regression revealed no significant association between maternal depression (B=52.2, 95% CI -18.2 122.6, p=0.15) or anxiety (B=17.1, 95% CI -74.6 108.7, p=0.72) and birth weight. Yet, low socio-economic status, female sex of the child, and younger maternal age were associated with lower birth weight. Multivariate logistic regression suggested no significant association between maternal depression (OR: 2.1, 95% CI 0.8 5.6, p=0.15) or anxiety (OR: 1.8, 95% CI 0.6 5.5, p=0.29) with PTB.

Conclusions

Our data suggests that depression and/or anxiety in the 3^rd trimester of pregnancy are not independent predictors of adverse birth outcomes in low obstetric risk women. The role of pregnancy complications as confounders or effect modifiers in studies of maternal CMD and their impact on birth outcomes should be investigated.     

Sorghum Insect Problems and Management

Sorghum (Sorghum bicolor) has high levels of starch,sugar,and fiber and is one of the most important energy crops in the world.Insect damage is one of the challenges that impacts sorghum biomass production.There are at least 150 insect species that can infest sorghum varieties worldwide.These insects can complete several generations within a growing season,they target various parts of sorghum plants at developmental stages,and they cause significant biomass losses.Genetic research has revealed the existence...     

Characterization of human embryonic stem cell lines by the International Stem Cell Initiative

The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue-nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.