Evidence For Concordance Research Articles

The partner paradox: How can we better understand shared cognitive decline in couples?

Shared cognitive decline among spouses remains in the early stages of being understood. In this commentary, we discuss Meng et al.'s systematic review and meta-analysis, which synthesizes the evidence for concordance of cognitive decline in couples. The study's methodology is robust and brings to light the challenges that persist within this field of research, namely the lack of specificity and standardization across outcomes and long-term follow-up. Here, we also situate the findings within the broader context of the many social influences on health and underscore the importance of dyadic preventive strategies and future longitudinal and mechanistic research.

Abstract PS05-03: MagSense® HER2, a Molecularly Targeted Magnetic Resonance Imaging Agent for the Detection of Axillary Nodal Metastasis in Subjects with Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Cancer

Abstract Background Precise nodal staging is critical in guiding systemic and regional treatments including surgery in the management of breast cancer. Regional nodal assessment includes axillary imaging (mostly by ultrasound) and lymph node sampling. Since imaging findings suggestive of nodal metastasis are based on size and morphologic changes and not specific to tumor type, pathologic confirmation through either biopsy or removal of sentinel lymph node (SLN) remains the gold standard. Imagion is developing the MagSense® HER2 Imaging Agent (MSH2IA), an anti-human epidermal growth factor receptor 2 (HER2) conjugated with iron oxide nanoparticles, for the detection of nodal metastasis in HER2+ breast cancer patients. MSH2IA is currently being investigated in a first-in-human phase 1 study (ACTRN12621000126819) in HER2+ breast cancer patients who are diagnosed to have suspicious nodes by conventional imaging. Methods The key objectives of the phase 1 study are safety and tolerability of MSH2IA and confirmation that MSH2IA drains to the axillary lymph nodes. The study also explores MSH2IA’s ability to detect metastatic nodes when used with magnetic resonance imaging (MRI), with tumor status assessed by standard tissue histopathology. All eligible subjects receive a 22.5 mg (iron equivalent) subareolar or peritumoral injection of MSH2IA. MRI of the axilla are obtained before and 24 to 72 hours after MSH2IA injection. Core biopsy or dissection of a node suspicious by ultrasound is obtained for histopathology assessments. After completing the first cohort of 6 subjects, the protocol was amended to include the insertion of an MRI compatible clip in a node suspicious by ultrasound to localize the suspicious node for core biopsy and postdose MRI scan. Review of MRI scans and histopathology are performed in respective central laboratories. Results Thirteen participants with HER2+ breast cancer have completed the study. MSH2IA appears safe and well tolerated. The imaging agent, as administered, is detectable by MRI and pathology, confirming that MSH2IA drains to the lymph nodes via the chosen route of administration. In postdose MRI scans, study central radiologists reported distinct and differentiable MRI appearance in morphologically normal and suspicious nodes. The presence of a distinct postdose MR image appearance was confirmed by a group of independent radiologists in a separate blinded review. While normal nodes appeared with homogeneous hypointensity, morphologically suspicious nodes showed partial irregular darkening and/or speckled heterogeneous hypointensity. In evaluable subjects, histopathology of the core biopsies obtained from the clipped nodes confirmed the presence of HER2+ nodal metastasis, providing preliminary evidence for node-level concordance between MRI vs pathology observations. Safety, imaging, and pathology results from all available subjects will be presented. This phase 1 study in Australia will be closing enrollment by July 31, 2023. A phase 2 study in the United States and elsewhere is being planned with the objectives of optimizing dose, schedule, and imaging parameters for best diagnostic performance for clinical utility. Conclusion Available data from the ongoing phase 1 study show that MSH2IA appears safe and drains to the axillary lymph nodes. MSH2IA displays a distinct and differentiable MRI appearance in nodes morphologically highly suspicious for tumor, which is confirmed to be HER2+ metastasis by histopathology by node level concordance. This data provides preliminary proof of principle for the mechanism of molecularly targeted MR imaging and suggests that MSH2IA has the potential to provide tumor-specific MR imaging not currently available in conventional axillary imaging. Citation Format: Jane Fox, Shanta Velaiutham, Natalie Yang, Eddie lau, Kowsi Murugappan, Beena Kumar, Alex Laslowski, Koushik Govindarajan, Steven Reich, Stephen Thomas, Nitika Neha, Marie Zhang, Isaac Bright. MagSense® HER2, a Molecularly Targeted Magnetic Resonance Imaging Agent for the Detection of Axillary Nodal Metastasis in Subjects with Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS05-03.

Performance Analysis of Driving Ability (P-Drive): Investigating Construct Validity and Concordance of Australasian Data.

On-road assessment is optimal for determining medical fitness-to-drive but unreliable if determined by global pass/fail decisions alone. Occupational therapists need standardized, psychometrically sound on-road scoring procedures. Performance Analysis of Driving Ability (P-Drive) is a promising on-road test developed in Sweden, but it has not been standardized for Australasia. We investigated the psychometric properties and concordance with an on-road decision of data gathered with the Australasian version of P-Drive. P-Drive was administered to older and cognitively impaired drivers (N = 134) aged 18 to 91 years (mean age 68) who were referred to 10 driving clinics in Australia and New Zealand to determine driving performance. Rasch analysis provided evidence for construct validity and concordance of the data gathered. An optimal cut-off score of 85 was set, yielding evidence of good sensitivity at 88% and specificity at 88%. The Australasian version of P-Drive produces valid and reliable data regarding on-road driving performance.

Context-dependent concordance between physiological divergence and phenotypic selection in sister taxa with contrasting phenology and mating systems.

The study of phenotypic divergence of, and selection on, functional traits in closely related taxa provides the opportunity to detect the role of natural selection in driving diversification. If the strength or direction of selection in field populations differs between taxa in a pattern that is consistent with the phenotypic difference between them, then natural selection reinforces the divergence. Few studies have sought evidence for such concordance for physiological traits. Herbarium specimen records were used to detect phenological differences between sister taxa independent of the effects on flowering time of long-term variation in the climate across collection sites. In the field, physiological divergence in photosynthetic rate, transpiration rate, and instantaneous water-use efficiency were recorded during vegetative growth and flowering in 13 field populations of two taxon pairs of Clarkia, each comprising a self-pollinating and a outcrossing taxon. Historically, each selfing taxon flowered earlier than its outcrossing sister taxon, independent of the effects of local long-term climatic conditions. Sister taxa differed in all focal traits, but the degree and (in one case) the direction of divergence depended on life stage. In general, self-pollinating taxa had higher gas exchange rates, consistent with their earlier maturation. In 6 of 18 comparisons, patterns of selection were concordant with the phenotypic divergence (or lack thereof) between sister taxa. Patterns of selection on physiological traits measured in heterogeneous conditions do not reliably reflect divergence between sister taxa, underscoring the need for replicated studies of the direction of selection within and among taxa.

Effects of Dispositional and Instructional Time Perspective on Academic Performance and Motivations Among Primary School Students: A Concordance Hypothesis

Background:Dispositional future time perspective (FTP) has been acknowledged for its benefits on academic outcomes. Lacking in the literature are 1) understanding of FTP in children, 2) experimental studies, and 3) evidence for time perspective concordance (i.e., matching between dispositional and instructional FTP yield favorable outcomes).Aims:Therefore, this study examined whether dispositional FTP, instructional FTP, and their interaction were associated with academic outcomes including reading performance and academic motivations among primary school students.Sample:The participants were grade-2 or grade-3 Hong Kong students (N= 92; Age:M= 8.05,SD= 0.72; 45% girls).Methods:The participants rated their dispositional FTP and were randomly assigned to draw a picture of their future or present self with the assumption that they study hard. The students then completed a reading task and rated their intrinsic motivation, extrinsic motivation, and amotivation.Results:Better reading scores were found in future-oriented students who drew a future self and those less future-oriented who drew a present self. No concordance effects were found on motivations. Nevertheless, the future-drawing task led to a greater extrinsic motivation than the present-drawing task.Conclusions:Some children may have developed FTP in their middle childhood. Academic motivations may be more malleable at a younger age. When facing incongruent instructional context, more cognitive resources may be drained to resolve the dissonance and, thus, compromise the cognitive performance. Rather than a predominant focus on future achievements, a balanced emphasis on present and future or a temporally tailored instructional context for individuals may be considered in primary education.

Genetic association of anthropometric traits with type 2 diabetes in ethnically endogamous Sindhi families.

BackgroundEthnically endogamous populations can shed light on the genetics of type 2 diabetes. Such studies are lacking in India. We conducted this study to determine the genetic and environmental contributions of anthropometric traits to type 2 diabetes risk in the Sindhi families in central India.MethodsWe conducted a family study in Indian Sindhi families with at least one case of type 2 diabetes. Variance components methods were used to quantify the genetic association of 18 anthropometric traits with eight type 2 diabetes related traits. Univariate and bivariate polygenic models were used to determine the heritability, genetic and environmental correlation of anthropometric traits with type 2 diabetes related traits.ResultsWe included 1,152 individuals from 112 phenotyped families. The ascertainment-bias corrected prevalence of type 2 diabetes was 35%. Waist circumference, hip circumference and the biceps, triceps, subscapular and medial calf skinfold thicknesses were polygenically and significantly associated with type 2 diabetes. The range of heritability of the anthropometric traits and type 2 diabetes related traits was 0.27–0.73 and 0.00–0.39, respectively. Heritability of type 2 diabetes as a discrete trait was 0.35. Heritability curves demonstrated a substantial local influence of type 2 diabetes related traits. Bivariate trait analyses showed that biceps and abdominal skinfold thickness and all waist-containing indexes were strongly genetically correlated with type 2 diabetes.ConclusionsIn this first study of Sindhi families, we found evidence for genetic and environmental concordance of anthropometric traits with type 2 diabetes. Future studies need to probe into the genetics of type 2 diabetes in this population.

Couples’ perceptions of each other’s depressive symptoms: Empathic accuracy and assumed similarity bias

The link between depressive symptoms and relationship functioning has been well-documented. Evidence for affective concordance in depressive symptoms between partners suggests that couples are aware of each other’s mood and symptoms; however, there have been no direct tests of the extent to which couples accurately perceive their partner’s mental health. The present study assessed spouses’ empathic accuracy and assumed similarity bias in rating each other’s depressive symptoms using the truth and bias actor-partner interdependence model for indistinguishable dyads. We hypothesized that husbands and wives would show significant assumed similarity but not significant empathic accuracy when rating their partner’s depressive symptoms. Participants were 55 racially and ethnically diverse heterosexual couples ( N = 110 individuals) with a child between the ages of 10–16 recruited from the community. Results did not provide evidence for empathic accuracy in rating a spouse’s depressive symptoms. Instead, we found significant assumed similarity, such that ratings of a spouse’s depressive symptoms were associated with one’s own level of depressive symptoms. We also found evidence of directional bias, such that, on average, spouses overestimated each other’s level of depressive symptoms. These preliminary findings suggest that couples may not be particularly attuned to their partner’s subjective ratings of depression-related thoughts, feelings, and behaviors. Future research should explore the processes accounting for partners’ perceptions of each other’s mental health, and the impact of these perceptions on relationship functioning.

Precision Nutrition and Reliability of Continuous Glucose Monitors: Insights From the PREDICT Study

Abstract Objectives The use of continuous glucose monitors (CGM) provides a more in-depth characterization of glycemic variation in response to environmental stimuli, but concerns about CGM reliability for categorizing glycemic responses to foods and meals exist. We sought to evaluate the concordance and reliability of two simultaneously worn CGM devices on postprandial glycemic responses. Methods We examined the correlation and coefficient of variation of the 2h glucose incremental area under the curve (iAUC) for 21,527 standardized and ad libitum meals consumed by 368 healthy participants from the PREDICT-1 Study. Included participants were simultaneously monitored with either two Abbott Freestyle Libre Pro devices (n = 339, same device group) or the combination of Abbott Freestyle Libre Pro and Dexcom G6 devices (n = 29, inter device group). Within-subject 2 h iAUC glucose meal rankings for paired CGM devices were assessed using the Kendal-tau measure for ranking concordance. Results The correlation coefficient of the 2 h glucose iAUC for paired CGM devices was 0.97 (95% CI, 0.96 to 0.97) for same device comparisons and 0.78 (0.76 to 0.80) for inter device comparisons. The coefficient of variation of the 2 h glucose iAUC for standardized meals was 5.1% (interquartile range, 2.2 to 10.1) for same device comparisons and 15.1% (5.9 to 31.2) for inter device comparisons. Similar results were observed for ad libitum meals with same and inter device coefficients of variation of 8.9% (3.3 to 21.3) and 24.2% (10.2 to 53.1%), respectively. Meal rankings for the 2 h glucose iAUC were concordant between paired CGM devices, with a mean Kendall rank correlation coefficient of 0.86 (sd = 0.07) for same device comparisons and 0.63 (sd = 0.011) for inter device comparisons. Conclusions These data provide evidence for repeatability and concordance for ranking of glycemic responses, and suggest that factors other than CGM sensors mostly drive within-subject meal categorization. Our findings are critical for identifying sources of variability in glycemic responses for the eventual implementation of precision nutrition. Funding Sources Zoe Global, UK Government Department of Health and Social Care, Wellcome Trust. National Institutes of Health.

An adverse outcome pathway on the disruption of retinoic acid metabolism leading to developmental craniofacial defects

Adverse outcome pathway (AOP) is a conceptual framework that links a molecular initiating event (MIE) via intermediate key events (KEs) with adverse effects (adverse outcomes, AO) relevant for risk assessment, through defined KE relationships (KERs). The aim of the present work is to describe a linear AOP, supported by experimental data, for skeletal craniofacial defects as the AO. This AO was selected in view of its relative high incidence in humans and the suspected relation to chemical exposure. We focused on inhibition of CYP26, a retinoic acid (RA) metabolizing enzyme, as MIE, based on robust previously published data. Conazoles were selected as representative stressors. Intermediate KEs are RA disbalance, aberrant HOX gene expression, disrupted specification, migration, and differentiation of neural crest cells, and branchial arch dysmorphology.We described the biological basis of the postulated events and conducted weight of evidence (WoE) assessments. The biological plausibility and the overall empirical evidence were assessed as high and moderate, respectively, the latter taking into consideration the moderate evidence for concordance of dose-response and temporal relationships. Finally, the essentiality assessment of the KEs, considered as high, supported the robustness of the presented AOP. This AOP, which appears of relevance to humans, thus contributes to mechanistic underpinning of selected test methods, thereby supporting their application in integrated new approach test methodologies and strategies and application in a regulatory context.

When ecological marginality is not geographically peripheral: exploring genetic predictions of the centre-periphery hypothesis in the endemic plant Lilium pomponium.

BackgroundQuantifying variation of genetic traits over the geographical range of species is crucial for understanding the factors driving their range dynamics. The center-periphery hypothesis postulates, and many studies support, the idea that genetic diversity decreases and genetic differentiation increases toward the geographical periphery due to population isolation. The effects of environmental marginality on genetic variation has however received much less attention.MethodsWe tested the concordance between geographical and environmental gradients and the genetic predictions of center-periphery hypothesis for endemic Lilium pomponium in the southern Alps.ResultsWe found little evidence for concordance between genetic variation and both geographical and environmental gradients. Although the prediction of increased differentiation at range limits is met, genetic diversity does not decrease towards the geographical periphery. Increased differentiation among peripheral populations, that are not ecologically marginal, may be explained by a decrease in habitat availability that reduces population connectivity. In contrast, a decrease of genetic diversity along environmental but not geographical gradients may be due to the presence of low quality habitats in the different parts of the range of a species that reduce effective population size or increase environmental constraints. As a result, environmental factors may affect population dynamics irrespective of distance from the geographical center of the range. In such situations of discordance between geographical and environmental gradients, the predictions of decreasing genetic diversity and increasing differentiation toward the geographical periphery may not be respected.

Exploring emotional dynamic within-person concordance across laboratory tasks: Moderation of between-person SES and sexual orientation

Current understandings of emotional concordance are still limited though it has been conceptualized and examined in various ways. We argue that emotional concordance could be better understood within individuals across real time in specific measurement contexts. The current study examined emotional dynamic within-person concordance within physiological subsystems and between physiological and expressive subsystems. We also explored the moderating roles of between-person factors on the within-person concordance and discordance. We found strong concordance within sympathetic indicators (PEP and CO), and between sympathetic and parasympathetic indicators (PEP and RSA), almost across all laboratory tasks. Evidence for concordance was generally weak between physiology and facial expression and have mostly been found between sympathetic indicator (PEP) and facial expressions. Participant socioeconomic status (SES) and sexual orientation seemed to moderate the emotional concordance. We discussed our findings across the various laboratory tasks in the current study.

A comparison of 7 commercial anti-SARS-CoV-2 antibody immunoassays.

Serological testing in SARS-CoV-2 infection is gaining both patients' and clinicians' attention. Antibody assessment has potential multidirectional utility, hampered by the scarcity of clinical validation studies of the tests available on the market. Therefore, this study aimed to provide some evidence on the clinical utility of anti-SARS-CoV-2 commercial assays, based on the comparison of the results obtained with different methods. The study included 52 samples from patients and healthy volunteers. The control samples (n = 20) were obtained during the SARS-CoV-2 pandemic. The case cohort consisted of 32 consecutive patients referred to the Diagnostyka medical laboratory for anti-SARS-CoV-2 antibody testing. For the purpose of this study, the MAGLUMI chemiluminescent immunoassay (CLIA) was chosen as a comparative method. All samples were tested with this method, as well as with the Euroimmun enzyme-linked immunosorbent assay (ELISA) and five different lateral flow immunoassays (LFIAs). The results obtained in this study provide evidence for high overall concordance between the comparative CLIA method and both ELISA and different LFIAs. The agreement between CLIA and LFIAs was 92.3-98.0% for IgG and 90.0-96.1% for IgM, depending on the kit. The concordance between CLIA and ELISA was 92.3% for IgG and 75.0% for IgA (compared to the MAGLUMI CLIA IgM). The results obtained in this study provide evidence for high overall concordance between the comparative CLIA method and different LFIAs. This could justify the use of LFIAs in some settings, where automated assays are not available, provided that some limitations are considered.

Maternal emotion dysregulation and physiological concordance in mother‐preschooler dyads

AbstractMaternal emotional and physiological dysregulation has been found to influence child stress physiology. This study characterizes diurnal cortisol and basal heart rate variability (HRV) patterns in a predominately high‐risk sample of mothers with a full range of emotion dysregulation and assessed the magnitude of concordance (N = 68 mother‐preschooler dyads). Overall, dyads exhibited concordance in evening salivary cortisol levels, but not for morning levels or HRV. Maternal emotion dysregulation was associated with maternal and child evening cortisol levels, child morning cortisol levels, and maternal HRV. Bootstrapping analyses showed that maternal emotion dysregulation was associated with higher child evening cortisol levels through its impact on mother evening cortisol levels. This study offers preliminary evidence for understanding child stress physiology and dyadic concordance in a sample of mothers with a range of emotion regulation capabilities.Highlights Maternal physiology may explain the association between maternal emotion dysregulation and child physiological patterns. Emotionally dysregulated mothers were oversampled and mothers and children's heart rate variability and cortisol were collected, with findings showing dyadic concordance in evening cortisol. This work highlights the importance of transdiagnostic approaches for examining concordance and child stress physiology.

Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses.

Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (r g = 0.23, P = 9.3 × 10−3), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10−3) and concordance in effect direction (P = 2.0 × 10−3) between the two diseases. Cross‐disease GWAS meta‐analysis highlighted 13 distinct loci associated at P ≤ 10−5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10−8, OR = 1.11, 95% CI = 1.07–1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross‐disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases.

Concordance between physiological arousal and emotion expression during fear in young children with autism spectrum disorders.

This study aimed to measure emotional expression and physiological arousal in response to fear in 21 children with autism spectrum disorders (43–75 months) and 45 typically developing children (41–81 months). Expressions of facial and bodily fear and heart rate arousal were simultaneously measured in response to a remote controlled robot (Laboratory Temperament Assessment Battery). Heart rate analyses revealed a main effect of task from baseline to fear (p < 0.001, ), no interaction effect and no effect for group. In addition, children with autism spectrum disorder showed intact facial and bodily expressions of fearful affect compared to typically developing children. With regard to the relationship between expression and arousal, the results provided evidence for concordance between expression and arousal in typically developing children (r = 0.45, n = 45, p < 0.01). For children with autism spectrum disorder, no significant correlation was found (r = 0.20, n = 21, p = 0.38). A moderation analysis revealed no significant interaction between expression and arousal for children with and without autism spectrum disorder (F(1, 62) = 1.23, p = 0.27, ), which might be the result of limited power. The current results give reason to further study concordance between expression and arousal in early autism spectrum disorder. Discordance might significantly impact social functioning and is an important topic in light of both early identification and treatment.

Effect of UDP-Glucuronosyltransferase (UGT) 1A Polymorphism (rs8330 and rs10929303) on Glucuronidation Status of Acetaminophen.

Interindividual variability in polymorphic uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) ascribed to genetic diversity is associated with relative glucuronidation level among individuals. The present research was aimed to study the effect of 2 important single nucleotide polymorphisms (SNPs; rs8330 and rs10929303) of UGT1A1 gene on glucuronidation status of acetaminophen in healthy volunteers (n = 109). Among enrolled volunteers, 54.13% were male (n = 59) and 45.87% were female (n = 50). The in vivo activity of UGT1A1 was investigated by high-performance liquid chromatography-based analysis of glucuronidation status (ie, acetaminophen and acetaminophen glucuronide) in human volunteers after oral intake of a single dose (1000 mg) of acetaminophen. The TaqMan SNP genotyping assay was used for UGT1A1 genotyping. The wild-type genotype (C/C) was observed the most frequent one for both SNPs (rs8330 and rs10929303) and associated with fast glucuronidator phenotypes. The distribution of variant genotype (G/G) for SNP rs8330 was observed in 5% of male and 8% of the female population; however, for SNP rs10929303, the G/G genotype was found in 8% of both genders. A trimodal distribution (fast, intermediate, and slow) based on phenotypes was observed. Among the male participants, the glucuronidation phenotypes were observed as 7% slow, 37% intermediate, and 56% fast glucuronidators; however, these findings for the females were slightly different as 8%, 32%, and 60% respectively. The k-statistics revealed a compelling evidence for good concordance between phenotype and genotype with a k value of 1.00 for SNP rs8330 and 0.966 for SNP rs10929303 in our population.

Comparison of DSM-5 and proposed ICD-11 criteria for PTSD with DSM-IV and ICD-10: changes in PTSD prevalence in military personnel

ABSTRACTBackground: Recently, changes have been introduced to the diagnostic criteria for posttraumatic stress disorder (PTSD) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD).Objectives:This study investigated the effect of the diagnostic changes made from DSM-IV to DSM-5 and from ICD-10 to the proposed ICD-11. The concordance of provisional PTSD prevalence between the diagnostic criteria was examined in a convenience sample of 100 members of the German Armed Forces.Method: Based on questionnaire measurements, provisional PTSD prevalence was assessed according to DSM-IV, DSM-5, ICD-10, and proposed ICD-11 criteria. Consistency of the diagnostic status across the diagnostic systems was statistically evaluated.Results: Provisional PTSD prevalence was the same for DSM-IV and DSM-5 (both 56%) and comparable under DSM-5 versus ICD-11 proposal (48%). Agreement between DSM-IV and DSM-5, and between DSM-5 and the proposed ICD-11, was high (both p < .001). Provisional PTSD prevalence was significantly increased under ICD-11 proposal compared to ICD-10 (30%) which was mainly due to the deletion of the time criterion. Agreement between ICD-10 and the proposed ICD-11 was low (p = .014).Conclusion: This study provides preliminary evidence for a satisfactory concordance between provisional PTSD prevalence based on the diagnostic criteria for PTSD that are defined using DSM-IV, DSM-5, and proposed ICD-11. This supports the assumption of a set of PTSD core symptoms as suggested in the ICD-11 proposal, when at the same time a satisfactory concordance between ICD-11 proposal and DSM was given. The finding of increased provisional PTSD prevalence under ICD-11 proposal in contrast to ICD-10 can be of guidance for future epidemiological research on PTSD prevalence, especially concerning further investigations on the impact, appropriateness, and usefulness of the time criterion included in ICD-10 versus the consequences of its deletion as proposed for ICD-11.

The association between lower educational attainment and depression owing to shared genetic effects? Results in ~25,000 subjects.

An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14,949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15,138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884,105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on ~120,000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status.

A genome wide meta-analysis study for identification of common variation associated with breast cancer prognosis.

ObjectiveGenome wide association studies (GWAs) of breast cancer mortality have identified few potential associations. The concordance between these studies is unclear. In this study, we used a meta-analysis of two prognostic GWAs and a replication cohort to identify the strongest associations and to evaluate the loci suggested in previous studies. We attempt to identify those SNPs which could impact overall survival irrespective of the age of onset.MethodsTo facilitate the meta-analysis and to refine the association signals, SNPs were imputed using data from the 1000 genomes project. Cox-proportional hazard models were used to estimate hazard ratios (HR) in 536 patients from the POSH cohort (Prospective study of Outcomes in Sporadic versus Hereditary breast cancer) and 805 patients from the HEBCS cohort (Helsinki Breast Cancer Study). These hazard ratios were combined using a Mantel-Haenszel fixed effects meta-analysis and a p-value threshold of 5×10−8 was used to determine significance. Replication was performed in 1523 additional patients from the POSH study.ResultsAlthough no SNPs achieved genome wide significance, three SNPs have significant association in the replication cohort and combined p-values less than 5.6×10−6. These SNPs are; rs421379 which is 556 kb upstream of ARRDC3 (HR = 1.49, 95% confidence interval (CI) = 1.27–1.75, P = 1.1×10−6), rs12358475 which is between ECHDC3 and PROSER2 (HR = 0.75, CI = 0.67–0.85, P = 1.8×10−6), and rs1728400 which is between LINC00917 and FOXF1.ConclusionsIn a genome wide meta-analysis of two independent cohorts from UK and Finland, we identified potential associations at three distinct loci. Phenotypic heterogeneity and relatively small sample sizes may explain the lack of genome wide significant findings. However, the replication at three SNPs in the validation cohort shows promise for future studies in larger cohorts. We did not find strong evidence for concordance between the few associations highlighted by previous GWAs of breast cancer survival and this study.

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