An Initial Test of the Tactic-First and Item-Order Hypotheses: Accounting for Response Discrepancies in Sexual Victimization Questionnaires

Reported prevalence rates of sexual violence range widely in the literature, even in the same sample when using two different questionnaires of the same construct. These discrepancies are concerning as they indicate we may be underestimating the rate of sexual violence and, therefore, resources and treatment for victims. Thus, the current study aimed to investigate two mechanisms that may contribute to differences in reported prevalence rates across the literature and discrepancies within studies: the tactic-first and item-order hypotheses. Participants were 265 MTurk workers whom all completed the Post-Refusal Sexual Persistence Scale (PRSPS), then were randomly assigned to one of two versions of a tactic-first Sexual Experiences Survey (T-SES). Experimental conditions varied in the item order of the T-SES, one condition received the traditional hierarchical item order (n = 130) while the other received a randomized item order (n = 135). Our results suggest strong support for the tactic-first hypothesis; victimization prevalence rates on the T-SES were double compared to the traditional SES (54.1 vs. 19.8%) in prior research. Further, in both conditions, victimization prevalence rates were statistically equivalent between the PRSPS (62.6%) and the tactic-first SESs (56.2 and 54.1%), χ2(1) \u3c 2.5, p ≈ .1–.7, contrary to prior research. We did not find support for the item-order hypothesis; there were few differences between item-order conditions. Our findings indicate that unintentional underreporting remains a threat to validity in sexual violence assessment, and continued research into the mechanisms of measurement is warranted

The Assessment of Forced Penetration: A Necessary and Further Step Toward Understanding Men’s Sexual Victimization and Women’s Perpetration

A unique form of sexual victimization that often goes undiscussed and, therefore, underassessed is that of being forced to penetrate another person (i.e., forced penetration). Due to forced penetration being a relatively novel addition to the definition of rape, there is a lack of assessment tools that identify forced penetration cases. Thus, the goal of this study was to assess the utility and validity of new items designed to assess forced penetration. More than 1,000 participants were recruited across three different studies to assess forced penetration victimization and perpetration. The rate of forced penetration victimization ranged from 4.51% to 10.62%. Among men who reported victimization of any type, 33.8% to 58.7% of victimized men reported experiencing forced penetration across the samples, suggesting this experience is common. All new and unique cases of sexual victimization identified by the forced penetration items were those of heterosexual men. These findings suggest that assessing for forced penetration would increase the reported prevalence rates of sexual victimization, particularly in heterosexual men (and correspondingly, rates of perpetration in women)

Predicting eating disorder and anxiety symptoms using disorder-specific and transdiagnostic polygenic scores for anorexia nervosa and obsessive-compulsive disorder

BACKGROUND: Clinical, epidemiological, and genetic findings support an overlap between eating disorders, obsessive-compulsive disorder (OCD), and anxiety symptoms. However, little research has examined the role of genetics in the expression of underlying phenotypes. We investigated whether the anorexia nervosa (AN), OCD, or AN/OCD transdiagnostic polygenic scores (PGS) predict eating disorder, OCD, and anxiety symptoms in a large developmental cohort in a sex-specific manner. METHODS: Using summary statistics from Psychiatric Genomics Consortium AN and OCD genome-wide association studies, we conducted an AN/OCD transdiagnostic genome-wide association meta-analysis. We then calculated AN, OCD, and AN/OCD PGS in participants from the Avon Longitudinal Study of Parents and Children to predict eating disorder, OCD, and anxiety symptoms, stratified by sex (combined N = 3212-5369 per phenotype). RESULTS: The PGS prediction of eating disorder, OCD, and anxiety phenotypes differed between sexes, although effect sizes were small. AN and AN/OCD PGS played a more prominent role in predicting eating disorder and anxiety risk than OCD PGS, especially in girls. AN/OCD PGS provided a small boost over AN PGS in the prediction of some anxiety symptoms. All three PGS predicted higher compulsive exercise across different developmental timepoints [β = 0.03 (s.e. = 0.01) for AN and AN/OCD PGS at age 14; β = 0.05 (s.e. = 0.02) for OCD PGS at age 16] in girls. CONCLUSIONS: Compulsive exercise may have a transdiagnostic genetic etiology, and AN genetic risk may play a role in the presence of anxiety symptoms. Converging with prior twin literature, our results also suggest that some of the contribution of genetic risk may be sex-specific

TNPO2 variants associate with human developmental delays, neurologic deficits, and dysmorphic features and alter TNPO2 activity in Drosophila

Transportin-2 (TNPO2) mediates multiple pathways including non-classical nucleocytoplasmic shuttling of >60 cargoes, such as developmental and neuronal proteins. We identified 15 individuals carrying de novo coding variants in TNPO2 who presented with global developmental delay (GDD), dysmorphic features, ophthalmologic abnormalities, and neurological features. To assess the nature of these variants, functional studies were performed in Drosophila. We found that fly dTnpo (orthologous to TNPO2) is expressed in a subset of neurons. dTnpo is critical for neuronal maintenance and function as downregulating dTnpo in mature neurons using RNAi disrupts neuronal activity and survival. Altering the activity and expression of dTnpo using mutant alleles or RNAi causes developmental defects, including eye and wing deformities and lethality. These effects are dosage dependent as more severe phenotypes are associated with stronger dTnpo loss. Interestingly, similar phenotypes are observed with dTnpo upregulation and ectopic expression of TNPO2, showing that loss and gain of Transportin activity causes developmental defects. Further, proband-associated variants can cause more or less severe developmental abnormalities compared to wild-type TNPO2 when ectopically expressed. The impact of the variants tested seems to correlate with their position within the protein. Specifically, those that fall within the RAN binding domain cause more severe toxicity and those in the acidic loop are less toxic. Variants within the cargo binding domain show tissue-dependent effects. In summary, dTnpo is an essential gene in flies during development and in neurons. Further, proband-associated de novo variants within TNPO2 disrupt the function of the encoded protein. Hence, TNPO2 variants are causative for neurodevelopmental abnormalities

Environmental and socio-demographic associates of children's active transport to school: a cross-sectional investigation from the URBAN Study

BACKGROUND: Active transport (e.g., walking, cycling) to school (ATS) can contribute to children's physical activity and health. The built environment is acknowledged as an important factor in understanding children's ATS, alongside parental factors and seasonality. Inconsistencies in methodological approaches exist, and a clear understanding of factors related to ATS remains equivocal. The purpose of this study was to gain a better understanding of associates of children's ATS, by considering the effects of daily weather patterns and neighbourhood walk ability and neighbourhood preferences (i.e., for living in a high or low walkable neighbourhood) on this behaviour. METHODS: Data were drawn from the Understanding Relationships between Activity and Neighbourhoods study, a cross-sectional study of physical activity and the built environment in adults and children in four New Zealand cities. Parents of participating children completed an interview and daily trip diary that assessed their child's mode of travel to school, household and individual demographic information, and parental neighbourhood preference. Daily weather data were downloaded from New Zealand's national climate database. Geographic information systems-derived variables were calculated for distance to school and neighbourhood walkability. Bivariate analyses were conducted with ATS and potential associates; factors related to ATS at p less than 0.20 were considered simultaneously in generalized estimation equation models, and backwards elimination of non-significant factors was conducted; city was treated as a fixed effect in all models. RESULTS: A total of 217 children aged 6.5-15 years participated in this study. Female sex, age, city, household income, limited/no car access, residing in zone of school, shorter distance to school, neighbourhood self selection, rainfall, and sunlight hours were simultaneously considered in multivariate generalised estimation equation modelling (all p less than 0.20 in bivariate analyses). After elimination of non-significant factors, age (p = 0.005), shorter distance to school (p less than 0.001), city (p = 0.03), and neighbourhood self selection (p = 0.04) remained significantly associated with ATS in the multivariate analysis. CONCLUSION: Distance to school is the prevailing environmental influencing factor on children's ATS. This study, in conjunction with previous research, suggests that school siting is likely an important associate of children's ATS

Genome Sequencing Reveals Widespread Virulence Gene Exchange among Human Neisseria Species

Commensal bacteria comprise a large part of the microbial world, playing important roles in human development, health and disease. However, little is known about the genomic content of commensals or how related they are to their pathogenic counterparts. The genus Neisseria, containing both commensal and pathogenic species, provides an excellent opportunity to study these issues. We undertook a comprehensive sequencing and analysis of human commensal and pathogenic Neisseria genomes. Commensals have an extensive repertoire of virulence alleles, a large fraction of which has been exchanged among Neisseria species. Commensals also have the genetic capacity to donate DNA to, and take up DNA from, other Neisseria. Our findings strongly suggest that commensal Neisseria serve as reservoirs of virulence alleles, and that they engage extensively in genetic exchange

Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer

Background Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes. Methods We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided. Results We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P Conclusion Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.Peer reviewe

Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21.

Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology

Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene