Newcomers and Old Timers: An Erroneous Assumption in Mental Health Services Research.

Based on the premise that treatment changes people in ways that are consequential for subsequent treatment-seeking, we question the validity of an unrecognized and apparently inadvertent assumption in mental health services research conducted within a psychiatric epidemiology paradigm. This homogeneity assumption statistically constrains the effects of potential determinants of recent treatment to be identical for former patients and previously untreated persons by omitting treatment history or modeling only main effects. We test this assumption with data from the 2001-2003 Collaborative Psychiatric Epidemiology Surveys; the weighted pooled sample is representative of noninstitutionalized U.S. adults (18+; analytic n = 19,227). Contrary to the homogeneity assumption, some associations with recent treatment are conditional on past treatment, including psychiatric disorder and race-ethnicity-measures of need and treatment disparities, respectively. We conclude that the widespread application of the homogeneity assumption probably masks differences in the determinants of recent use between previously untreated persons and former patients.

Discovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individuals.

BACKGROUND: The genetic etiology of human lipid quantitative traits is not fully elucidated, and interactions between variants may play a role. We performed a gene-centric interaction study for four different lipid traits: low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG). RESULTS: Our analysis consisted of a discovery phase using a merged dataset of five different cohorts (n = 12,853 to n = 16,849 depending on lipid phenotype) and a replication phase with ten independent cohorts totaling up to 36,938 additional samples. Filters are often applied before interaction testing to correct for the burden of testing all pairwise interactions. We used two different filters: 1. A filter that tested only single nucleotide polymorphisms (SNPs) with a main effect of p < 0.001 in a previous association study. 2. A filter that only tested interactions identified by Biofilter 2.0. Pairwise models that reached an interaction significance level of p < 0.001 in the discovery dataset were tested for replication. We identified thirteen SNP-SNP models that were significant in more than one replication cohort after accounting for multiple testing. CONCLUSIONS: These results may reveal novel insights into the genetic etiology of lipid levels. Furthermore, we developed a pipeline to perform a computationally efficient interaction analysis with multi-cohort replication.

Implicit Reasons for Disclosure of the Use of Complementary Health Approaches (CHA): a Consumer Commitment Perspective.

BACKGROUND: Disclosure of the use of complementary health approaches (CHA) is an important yet understudied health behavior with important implications for patient care. Yet research into disclosure of CHA has been atheoretical and neglected the role of health beliefs. PURPOSE: Using a consumer commitment model of CHA use as a guiding conceptual framework, the current study tests the hypotheses that perceived positive CHA outcomes (utilitarian values) and positive CHA beliefs (symbolic values) are associated with disclosure of CHA to conventional care providers in a nationally representative US sample. METHODS: From a sample of 33,594 with CHA use information from the 2012 National Health Interview Survey (NHIS), a subsample of 7348 who used CHA within the past 12 months was analyzed. The 2012 NHIS is a cross-sectional survey of the non-institutionalized US adult population, which includes the most recent nationally representative CHA use data. RESULTS: The 63.2% who disclosed CHA use were older, were less educated, and had visited a health care provider in the past year. Weighted logistic regression analyses controlling for demographic variables revealed that those who disclosed were more likely to report experiencing positive psychological (improved coping and well-being) and physical outcomes (better sleep, improved health) from CHA and hold positive CHA-related beliefs. CONCLUSIONS: CHA users who perceive physical and psychological benefits from CHA use and who hold positive attitudes towards CHA are more likely to disclose their CHA use. Findings support the relevance of a consumer commitment perspective for understanding CHA disclosure and suggest CHA disclosure as an important proactive health behavior that warrants further attention.

Human papillomavirus (HPV) awareness and vaccine receptivity among Senegalese adolescents.

OBJECTIVE: To examine HPV vaccine awareness and receptivity among adolescents and young adults in Senegal. METHODS: Participants from six high schools and five community centres across five regions of Senegal (n = 2286) completed a self-administered questionnaire in October and November 2014. The study assessed HPV awareness and receptivity towards receiving the HPV vaccine. Multivariable logistic regression explored statistically significant relationships between the predictor variables and both outcomes. RESULTS: Twenty-seven percent had heard of HPV. Among those who had heard of HPV (n = 616), only 28% indicated willingness to vaccinate. Multivariable analysis showed that respondents from rural areas had 63% higher odds (95% CI: 1.24, 2.12) of having heard of HPV than those in urban areas. Respondents with fathers who had completed higher education had 41% higher odds (95% CI: 1.04, 1.92) of being aware of HPV (P < 0.05); however, every level of father's education (as compared to no education at all) was negatively associated with willingness to vaccinate. Respondents who had previously spoken to a healthcare professional about the HPV vaccine had 80% higher odds (95% CI: 1.16, 2.81) of willingness to vaccinate than those who did not speak to a provider about the vaccine. CONCLUSIONS: Healthcare providers and parents are important stakeholders in disseminating HPV vaccine information. Given the overall low levels of awareness, there is a great opportunity for public health communication efforts to craft health messaging and information in a way to maximise receptivity, outlining benefits and providing information on the minimal risks associated with the vaccine.

Understanding where and why Senegalese adolescents and young adults access health information: A mixed methods study examining contextual and personal influences on health information seeking.

BACKGROUND: Adolescent and young adult years are critical to the development of behaviors that influence health across the life course. To reveal which health communication channels should be used to effectively reach and influence younger populations in Senegal, we used a mixed methods approach to identify and interpret the multifaceted influences surrounding where and why this population accesses health information. METHODS: We conducted 16 focus group discussions among adolescents and young adults in Senegal in September 2012. We then collected survey data from a larger, more diverse sample of Senegalese youth in October-November 2014. RESULTS: Our results demonstrate that information sources vary by health topic, differential access, age, and other demographics. While there is a greater perception of credibility and usefulness in information received from health professionals, stigma remains a barrier for obtaining information about HIV/AIDS from health centers. Older youth are also less likely to seek health information from adults, which may be influenced by preferred use of information technologies, especially for information about taboo health topics. CONCLUSIONS: Our findings support multi-pronged, targeted approaches to health communication efforts. We recommend that doctors continue to provide actionable information about preventing or treating specific diseases, whereas teachers should educate youth about general health topics and health promotion behaviors. The results suggest that traditional mass media, such as radio and television, are the best communication channels for information about HIV and sexual/reproductive health, especially for older adolescents and young adults.

A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration.

Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci; of which, 18 were newly identified. There were no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.

Molecular Characterization of the NLRC4 Expression in Relation to Interleukin-18 Levels.

BACKGROUND: Interleukin-18 (IL-18) is a pleiotropic cytokine centrally involved in the cytokine cascade with complex immunomodulatory functions in innate and acquired immunity. Circulating IL-18 concentrations are associated with type 2 diabetes mellitus, cardiovascular events, and diverse inflammatory and autoimmune disorders. METHODS AND RESULTS: To identify causal variants affecting circulating IL-18 concentrations, we applied various omics and molecular biology approaches. By genome-wide association study, we confirmed association of IL-18 levels with a single nucleotide polymorphism in the untranslated exon 2 of the inflammasome component NLRC4 (NLR family, caspase recruitment domain-containing 4) gene on chromosome 2 (rs385076; P=2.4 × 10(-45)). Subsequent molecular analyses by gene expression analysis and reporter gene assays indicated an effect of rs385076 on NLRC4 expression and differential isoform usage by modulating binding of the transcription factor PU.1. CONCLUSIONS: Our study provides evidence for the functional causality of single nucleotide polymorphism rs385076 within the NLRC4 gene in relation to IL-18 activation.

Rare and low-frequency variants and their association with plasma levels of fibrinogen, FVII, FVIII, and vWF.

Fibrinogen, coagulation factor VII (FVII), and factor VIII (FVIII) and its carrier von Willebrand factor (vWF) play key roles in hemostasis. Previously identified common variants explain only a small fraction of the trait heritabilities, and additional variations may be explained by associations with rarer variants with larger effects. The aim of this study was to identify low-frequency (minor allele frequency [MAF] ≥0.01 and <0.05) and rare (MAF <0.01) variants that influence plasma concentrations of these 4 hemostatic factors by meta-analyzing exome chip data from up to 76,000 participants of 4 ancestries. We identified 12 novel associations of low-frequency (n = 2) and rare (n = 10) variants across the fibrinogen, FVII, FVIII, and vWF traits that were independent of previously identified associations. Novel loci were found within previously reported genes and had effect sizes much larger than and independent of previously identified common variants. In addition, associations at KCNT1, HID1, and KATNB1 identified new candidate genes related to hemostasis for follow-up replication and functional genomic analysis. Newly identified low-frequency and rare-variant associations accounted for modest amounts of trait variance and therefore are unlikely to increase predicted trait heritability but provide new information for understanding individual variation in hemostasis pathways.

Ascaris lumbricoides infection and its relation to environmental factors in the Mbeya region of Tanzania, a cross-sectional, population-based study.

BACKGROUND: With one quarter of the world population infected, the intestinal nematode Ascaris lumbricoides is one of the most common infectious agents, especially in the tropics and sub-tropics. Infection is caused by oral intake of eggs and can cause respiratory and gastrointestinal problems. To identify high risk areas for intervention, it is necessary to understand the effects of climatic, environmental and socio-demographic conditions on A. lumbricoides infection. METHODOLOGY: Cross-sectional survey data of 6,366 study participants in the Mbeya region of South-Western Tanzania were used to analyze associations between remotely sensed environmental data and A. lumbricoides infection. Non-linear associations were accounted for by using fractional polynomial regression, and socio-demographic and sanitary data were included as potential confounders. PRINCIPAL FINDINGS: The overall prevalence of A. lumbricoides infection was 6.8%. Our final multivariable model revealed a significant non-linear association between rainfall and A. lumbricoides infection with peak prevalences at 1740 mm of mean annual rainfall. Mean annual land surface temperature during the day was linearly modeled and negatively associated with A. lumbricoides infection (odds ratio (OR) = 0.87, 95% confidence interval (CI) = 0.78-0.97). Furthermore, age, which also showed a significant non-linear association (infection maximum at 7.7 years), socio-economic status (OR = 0.82, CI = 0.68-0.97), and latrine coverage around the house (OR = 0.80, CI = 0.67-0.96) remained in the final model. CONCLUSIONS: A. lumbricoides infection was associated with environmental, socio-demographic and sanitary factors both in uni- and multivariable analysis. Non-linear analysis with fractional polynomials can improve model fit, resulting in a better understanding of the relationship between environmental conditions and helminth infection, and more precise predictions of high prevalence areas. However, socio-demographic determinants and sanitary conditions should also be considered, especially when planning public health interventions on a smaller scale, such as the community level.

Leveraging cross-species transcription factor binding site patterns: from diabetes risk loci to disease mechanisms.

Genome-wide association studies have revealed numerous risk loci associated with diverse diseases. However, identification of disease-causing variants within association loci remains a major challenge. Divergence in gene expression due to cis-regulatory variants in noncoding regions is central to disease susceptibility. We show that integrative computational analysis of phylogenetic conservation with a complexity assessment of co-occurring transcription factor binding sites (TFBS) can identify cis-regulatory variants and elucidate their mechanistic role in disease. Analysis of established type 2 diabetes risk loci revealed a striking clustering of distinct homeobox TFBS. We identified the PRRX1 homeobox factor as a repressor of PPARG2 expression in adipose cells and demonstrate its adverse effect on lipid metabolism and systemic insulin sensitivity, dependent on the rs4684847 risk allele that triggers PRRX1 binding. Thus, cross-species conservation analysis at the level of co-occurring TFBS provides a valuable contribution to the translation of genetic association signals to disease-related molecular mechanisms.

Hookworm infection and environmental factors in mbeya region, Tanzania: a cross-sectional, population-based study.

BACKGROUND: Hookworm disease is one of the most common infections and cause of a high disease burden in the tropics and subtropics. Remotely sensed ecological data and model-based geostatistics have been used recently to identify areas in need for hookworm control. METHODOLOGY: Cross-sectional interview data and stool samples from 6,375 participants from nine different sites in Mbeya region, south-western Tanzania, were collected as part of a cohort study. Hookworm infection was assessed by microscopy of duplicate Kato-Katz thick smears from one stool sample from each participant. A geographic information system was used to obtain remotely sensed environmental data such as land surface temperature (LST), vegetation cover, rainfall, and elevation, and combine them with hookworm infection data and with socio-demographic and behavioral data. Uni- and multivariable logistic regression was performed on sites separately and on the pooled dataset. PRINCIPAL FINDINGS: Univariable analyses yielded significant associations for all ecological variables. Five ecological variables stayed significant in the final multivariable model: population density (odds ratio (OR) = 0.68; 95% confidence interval (CI) = 0.63-0.73), mean annual vegetation density (OR = 0.11; 95% CI = 0.06-0.18), mean annual LST during the day (OR = 0.81; 95% CI = 0.75-0.88), mean annual LST during the night (OR = 1.54; 95% CI = 1.44-1.64), and latrine coverage in household surroundings (OR = 1.02; 95% CI = 1.01-1.04). Interaction terms revealed substantial differences in associations of hookworm infection with population density, mean annual enhanced vegetation index, and latrine coverage between the two sites with the highest prevalence of infection. CONCLUSION/SIGNIFICANCE: This study supports previous findings that remotely sensed data such as vegetation indices, LST, and elevation are strongly associated with hookworm prevalence. However, the results indicate that the influence of environmental conditions can differ substantially within a relatively small geographic area. The use of large-scale associations as a predictive tool on smaller scales is therefore problematic and should be handled with care.