Association Test Research Articles

The impact of incident stroke on cognitive trajectories in later life

BackgroundCognitive impairment is common after stroke, and a large proportion of stroke patients will develop dementia. However, there have been few large prospective studies which have assessed cognition both prior to and after stroke. This study aims to determine the extent to which incident stroke impacts different domains of cognitive function in a longitudinal cohort of older community-dwelling individuals.Methods19,114 older individuals without cardiovascular disease or major cognitive impairment were recruited and followed over a maximum 11 years. Stroke included ischaemic and haemorrhagic stroke and was adjudicated by experts. Cognitive function was assessed regularly using Modified Mini-Mental State Examination (3MS), Hopkins Verbal Learning Test–Revised (HVLT-R), Symbol Digit Modalities Test (SDMT), and Controlled Oral Word Association Test (COWAT). Linear mixed models were used to investigate the change in cognition at the time of stroke and decline in cognitive trajectories following incident stroke.ResultsDuring a median follow-up period of 8.4 [IQR: 7.2, 9.6] years, 815 (4.3%) participants experienced a stroke. Over this time, there was a general decline observed in 3MS, HVLT-R delayed recall, and SDMT scores across participants. However, for individuals who experienced a stroke, there was a significantly greater decline across all cognitive domains immediately after the event immediately after the event (3MS: -1.03 [95%CI: -1.45, -0.60]; HVLT-R: -0.47 [-0.70, -0.24]; SDMT: -2.82 [-3.57, -2.08]; COWAT: -0.67 [-1.04, -0.29]) and a steeper long-term decline for three of these domains (3MS -0.62 [-0.88, -0.35]; COWAT: -0.30 [-0.46, -0.14]); HVLT-R: -0.12 [95%CI, -0.70, -0.24]). However individuals with stroke experienced no longer-term decline in SDMT compared to the rest of the participants.ConclusionsThese findings highlight the need for comprehensive neuropsychology assessments for ongoing monitoring of cognition following incident stroke; and potential early intervention.

The Ups and Downs of Black and White: Do Sensorimotor Metaphors Reflect an Evolved Perceptual Interface?

ABSTRACT The Implicit Association Test (IAT) was used to measure population levels of conceptual alignment among two polar sensory metaphors and clusters of concepts to which they are commonly applied. A total of 873 participants were tested online, to compare within- and between-cluster alignments of concepts associated with two different polar sensory metaphors (up/down and black/white). IAT results were sensitive to semantic alignments that were also picked up by Latent Semantic Analysis (LSA) using a large-scale corpus of English. However, even with these semantic alignments taken into account, the dual categorization results demonstrated strong metaphor-cluster alignments over and above the predictions of LSA. It is proposed that, rather than ontogenetic development of metaphoric concepts based on sensorimotor experience, conventionalized sensorimotor metaphors in language may be cognitive tools that provide language learners with insights supported by conceptual properties of a phylogenetically evolved perceptual interface.

Emotional body representations: more pronounced effect of hands at a more explicit level of awareness.

To understand conditions such as body dysmorphic disorder, we need to understand healthy individuals' perceptual, conceptual, and emotional representations of their bodies. Not much is known about the differences in these representations across body districts, for example, hands, feet, and whole-body, despite their differences at sensory and functional levels. To understand this, we developed more implicit and explicit measures of body satisfaction for these body districts. Sixty-seven participants (age M = 30.66, SD = 11.19) completed a series of online Implicit Association Tests (IAT) and a Body Image Satisfaction Visual Analogue Scale (BISVAS; explicit) for each body district (hands/feet/whole body). The results show no differences in the more implicit level of awareness in hands, feet and whole body, while differences are apparent at a more explicit level of awareness, with higher scores for body image satisfaction for the hands than the whole body and marginally significant lower scores for feet than hands. Those findings suggest that visual attention, level of concern attributed to a body district, and disgust drivers are possible factors affecting the experience of attitudinal body image satisfaction.

Robust differential expression testing for single-cell CRISPR screens at low multiplicity of infection.

Single-cell CRISPR screens (perturb-seq) link genetic perturbations to phenotypic changes in individual cells. The most fundamental task in perturb-seq analysis is to test for association between a perturbation and a count outcome, such as gene expression. We conduct the first-ever comprehensive benchmarking study of association testing methods for low multiplicity-of-infection (MOI) perturb-seq data, finding that existing methods produce excess false positives. We conduct an extensive empirical investigation of the data, identifying three core analysis challenges: sparsity, confounding, and model misspecification. Finally, we develop an association testing method - SCEPTRE low-MOI - that resolves these analysis challenges and demonstrates improved calibration and power.

Improved implicit self-esteem is associated with extended antidepressant effects following a novel synergistic intervention.

In a previously published randomized controlled trial, automated self-association training (ASAT), a novel digital intervention, was found to extend the rapid antidepressant effect of a single infusion of ketamine for at least 30 days. In this secondary analysis, we aimed to understand the potential role of implicit self-esteem in the combined antidepressant effect of ketamine and ASAT training, by investigating the novel synergistic treatment's effects on implicit self-associations and their relation to symptom improvement. A total of 154 adults (ages 18-60) with treatment-resistant unipolar depression and lower-than-normative explicit self-esteem were randomized in a double-blind, parallel-arm design to receive one of three treatment allocations: an active/active treatment combination consisting of one infusion of ketamine (0.5 mg/kg) followed by four days of ASAT ( ~ 30-40 min/day), or one of two control arms that lacked either the active drug or the active behavioral component. The Implicit Association Test (IAT) was used to behaviorally assess the strength of association between self-related stimuli and negative concepts. Linear regression models were used to test the relationship between group assignment, IAT scores acquired immediately post-treatment, and both acute and extended clinical outcomes (% change in Montgomery-Asberg Depression Rating Scale scores, relative to pre-treatment baseline) in the trial. The group assigned to ketamine + ASAT intervention, compared to the other groups, had a pattern of IAT scores indicating more positive self-associations immediately after treatment relative to the control arms (F(1, 131) = 3.979; p = 0.048). In regression models, IAT scores tracked with concurrent (acute post-treatment) % change in MADRS scores across all treatment arms (p = 0.001), and mediated more extended (Day 30) depression improvements specifically for the ketamine+ASAT arm (group * IAT interaction term: β = -0.201; p = 0.049). Our findings suggest that changing implicit self-worth during a post-ketamine 'plasticity window' is one key mechanism whereby the novel ketamine+ASAT treatment combination exerts its antidepressant benefit, confirming the intended treatment target at the level of implicit cognition. Future studies should seek to further enhance the reliability of the biobehavioral intervention's impact on implicit cognition, as this mechanism appears linked to the intervention's enduring clinical benefits.

Automatically Distinguishing People’s Explicit and Implicit Attitude Bias by Bridging Psychological Measurements with Sentiment Analysis on Large Corpora

Social psychological studies show that people’s explicit attitude bias in public expression can differ from their implicit attitude bias in mind. However, the current automatic attitude analysis does not distinguish between explicit and implicit attitude bias. Simulating the psychological measurements of explicit and implicit attitude bias, i.e., self-report assessment (SRA) and implicit association test (IAT), we propose an automatic language-based analysis to distinguish explicit and implicit attitude bias in a large population. By connecting the criteria of SRA and IAT with the statements containing patterns of special words, we derive explicit and implicit attitude bias with the sentiment scores of the statements, which are obtained by pre-trained machine-learning methods. Extensive experiments on four English and Chinese corpora and four pairs of concepts show that the attitude biases obtained by our method on a large population are consistent with those of traditional psychological experiments in the costly small-scale experiments. The maximum gap between the sentiment scores of explicit and implicit biases reaches 0.9329. Furthermore, we achieve new findings on the difference between the evolution of explicit and implicit attitude bias. The maximum variance gap of sentiment scores in the dynamic changes between explicit and implicit biases reaches 0.249.

Genetic association and transferability for urinary albumin-creatinine ratio as a marker of kidney disease in four Sub-Saharan African populations and non-continental individuals of African ancestry

BackgroundGenome-wide association studies (GWAS) have predominantly focused on populations of European and Asian ancestry, limiting our understanding of genetic factors influencing kidney disease in Sub-Saharan African (SSA) populations. This study presents the largest GWAS for urinary albumin-to-creatinine ratio (UACR) in SSA individuals, including 8,970 participants living in different African regions and an additional 9,705 non-resident individuals of African ancestry from the UK Biobank and African American cohorts.MethodsUrine biomarkers and genotype data were obtained from two SSA cohorts (AWI-Gen and ARK), and two non-resident African-ancestry studies (UK Biobank and CKD-Gen Consortium). Association testing and meta-analyses were conducted, with subsequent fine-mapping, conditional analyses, and replication studies. Polygenic scores (PGS) were assessed for transferability across populations.ResultsTwo genome-wide significant (P < 5 × 10−8) UACR-associated loci were identified, one in the BMP6 region on chromosome 6, in the meta-analysis of resident African individuals, and another in the HBB region on chromosome 11 in the meta-analysis of non-resident SSA individuals, as well as the combined meta-analysis of all studies. Replication of previous significant results confirmed associations in known UACR-associated regions, including THB53, GATM, and ARL15. PGS estimated using previous studies from European ancestry, African ancestry, and multi-ancestry cohorts exhibited limited transferability of PGS across populations, with less than 1% of observed variance explained.ConclusionThis study contributes novel insights into the genetic architecture of kidney disease in SSA populations, emphasizing the need for conducting genetic research in diverse cohorts. The identified loci provide a foundation for future investigations into the genetic susceptibility to chronic kidney disease in underrepresented African populations Additionally, there is a need to develop integrated scores using multi-omics data and risk factors specific to the African context to improve the accuracy of predicting disease outcomes.

Genetic Architectures of Adolescent Depression Trajectories in 2 Longitudinal Population Cohorts

Adolescent depression is characterized by diverse symptom trajectories over time and has a strong genetic influence. Research has determined genetic overlap between depression and other psychiatric conditions; investigating the shared genetic architecture of heterogeneous depression trajectories is crucial for understanding disease etiology, prediction, and early intervention. To investigate univariate and multivariate genetic risk for adolescent depression trajectories and assess generalizability across ancestries. This cohort study entailed longitudinal growth modeling followed by polygenic risk score (PRS) association testing for individual and multitrait genetic models. Two longitudinal cohorts from the US and UK were used: the Adolescent Brain and Cognitive Development (ABCD; N = 11 876) study and the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 8787) study. Included were adolescents with genetic information and depression measures at up to 8 and 4 occasions, respectively. Study data were analyzed January to July 2023. Trajectories were derived from growth mixture modeling of longitudinal depression symptoms. PRSs were computed for depression, anxiety, neuroticism, bipolar disorder, schizophrenia, attention-deficit/hyperactivity disorder, and autism in European ancestry. Genomic structural equation modeling was used to build multitrait genetic models of psychopathology followed by multitrait PRS. Depression PRSs were computed in African, East Asian, and Hispanic ancestries in the ABCD cohort only. Association testing was performed between all PRSs and trajectories for both cohorts. A total sample size of 14 112 adolescents (at baseline: mean [SD] age, 10.5 [0.5] years; 7269 male sex [52%]) from both cohorts were included in this analysis. Distinct depression trajectories (stable low, adolescent persistent, increasing, and decreasing) were replicated in the ALSPAC cohort (6096 participants; 3091 female [51%]) and ABCD cohort (8016 participants; 4274 male [53%]) between ages 10 and 17 years. Most univariate PRSs showed significant uniform associations with persistent trajectories, but fewer were significantly associated with intermediate (increasing and decreasing) trajectories. Multitrait PRSs-derived from a hierarchical factor model-showed the strongest associations for persistent trajectories (ABCD cohort: OR, 1.46; 95% CI, 1.26-1.68; ALSPAC cohort: OR, 1.34; 95% CI, 1.20-1.49), surpassing the effect size of univariate PRS in both cohorts. Multitrait PRSs were associated with intermediate trajectories but to a lesser extent (ABCD cohort: hierarchical increasing, OR, 1.27; 95% CI, 1.13-1.43; decreasing, OR, 1.23; 95% CI, 1.09-1.40; ALSPAC cohort: hierarchical increasing, OR, 1.16; 95% CI, 1.04-1.28; decreasing, OR, 1.32; 95% CI, 1.18-1.47). Transancestral genetic risk for depression showed no evidence for association with trajectories. Results of this cohort study revealed a high multitrait genetic loading of persistent symptom trajectories, consistent across traits and cohorts. Variability in univariate genetic association with intermediate trajectories may stem from environmental factors. Multitrait genetics may strengthen depression prediction models, but more diverse data are needed for generalizability.

Does identity as a drinker predict problem recognition motivation in harmful drinkers?

Harmful drinking is associated with significant negative health and social outcomes, but drinkers are reticent to recognise personal drinking problems, hindering natural recovery or help-seeking. Recent evidence suggests that social identity as a drinker is associated with various drinking-related factors but has not been examined in relation to likelihood of problem recognition. In a group of ninety-six harmful drinkers (61 females, M age = 34 years) we explored how identity components associated with ingroup self-investment and ingroup self-definition in combination with implicit identity as a drinker accounted for degrees of problem recognition. In addition to demographic information, addiction experience and drinking behaviour (AUDIT), respondents completed measures of ingroup self-investment (identity centrality, solidarity, and satisfaction), ingroup self-definition (ingroup homogeneity and self-stereotyping), a “self as drinker” identity implicit association test and problem recognition (four items from the Stages of Change Readiness and Treatment Eagerness Scale). After controlling for possible covariates (age, gender and alcohol addiction experience) increased problem recognition was accounted for by explicit and not implicit identity components. More specifically, increasing perceived chronic saliency of one's drinker identity (self-investment in the drinker ingroup) and not an implicit association between the self and being a drinker was related to increased likelihood of problem recognition. This suggests that how chronically and explicitly accessible the identity of the drinker is for individuals might operate to stimulate the willingness or motivation to recognise potential drinking related harm.

Identification of the Molecular Components of Enhancer-Mediated Gene Expression Variation in Multiple Tissues Regulating Blood Pressure.

Inter-individual variation in blood pressure (BP) arises in part from sequence variants within enhancers modulating the expression of causal genes. We propose that these genes, active in tissues relevant to BP physiology, can be identified from tissue-level epigenomic data and genotypes of BP-phenotyped individuals. We used chromatin accessibility data from the heart, adrenal, kidney, and artery to identify cis-regulatory elements (CREs) in these tissues and estimate the impact of common human single-nucleotide variants within these CREs on gene expression, using machine learning methods. To identify causal genes, we performed a gene-wise association test. We conducted analyses in 2 separate large-scale cohorts: 77 822 individuals from the Genetic Epidemiology Research on Adult Health and Aging and 315 270 individuals from the UK Biobank. We identified 309, 259, 331, and 367 genes (false discovery rate <0.05) for diastolic BP and 191, 184, 204, and 204 genes for systolic BP in the artery, kidney, heart, and adrenal, respectively, in Genetic Epidemiology Research on Adult Health and Aging; 50% to 70% of these genes were replicated in the UK Biobank, significantly higher than the 12% to 15% expected by chance (P<0.0001). These results enabled tissue expression prediction of these 988 to 2875 putative BP genes in individuals of both cohorts to construct an expression polygenic score. This score explained ≈27% of the reported single-nucleotide variant heritability, substantially higher than expected from prior studies. Our work demonstrates the power of tissue-restricted comprehensive CRE analysis, followed by CRE-based expression prediction, for understanding BP regulation in relevant tissues and provides dual-modality supporting evidence, CRE and expression, for the causality genes.

Climate-Related Financial Risk: Insights from a Semisystematic Review of the Literature and Implications for Financial Reporting

Synopsis The research problem This paper provides a semisystematic review of the literature on climate-related financial risk, with particular emphasis on whether that risk is adequately priced by financial markets and the implications of that risk assessment for financial reporting. Motivation This paper was motivated by a strong perception that financial markets have become increasingly exposed to the perils of climate change, and a concern for whether the rapid expansion of the literature on this topic sufficiently addresses financial markets’ correct pricing of the uncertainties inherent in these perils. Our particular goals were to understand the expansion of this literature, identify the originating and influential works that may have spurred this expansion, and provide new directions for research. The research question Our paper reviews the research on whether climate-related financial risk is adequately priced by the financial markets. Target population We examined a comprehensive sample of articles on climate-related financial risk published in the Financial Times’ Top 50 (FT50) accounting, finance, management, and business ethics journals over three decades, ending in 2022. Our analysis of the evolution of knowledge on climate-related financial risk also includes studies in non-FT50 journals (prior works) that may have spurred subsequent work in FT50 journals; non-FT50 journals (derivative works) that are inspired by the studies in FT50 journals; and set of studies that are similar to those in FT50 journals in terms of the topic (similar works) published in an array of non-FT50 journals. Adopted methodology We conducted a semisystematic review of knowledge flow based on bibliographic coupling, cocitation, and direct citation. Analyses We reviewed FT50 articles to examine the topics, methods, samples, and results. We compared FT50 articles with non-FT50 articles to explore their respective number of publications and average citations over time. We also examined the extent to which the FT50 and non-FT50 journals included accounting papers and the extent to which the top 20 papers, based on their impact (defined as the number of times a paper was considered an influential work by the FT50 journal papers), included accounting papers. Findings Compared to non-FT50 journals, we find that FT50 journals largely ignored climate-related financial risk until about 2010, and that the average citation of an FT50 publication was lower than a non-FT50 publication until around 2017. The fraction of FT50 and non-FT50 accounting journals publishing on climate-related financial risk remained low across all years. Moreover, the top 20 studies, based on their impact, included very few accounting papers. Our review of the content of the FT50 studies identifies traits of the literature that limit its generalizability, namely, a heavy emphasis on samples of U.S. corporations and the extensive use of association tests to develop the findings. Our review of the literature on the pricing effects of climate-related financial risk suggests that financial markets only partially price this risk and that fundamental questions relevant to policy remain unanswered.

The landscape of rare genetic variation associated with inflammatory bowel disease and Parkinson’s disease comorbidity

BackgroundInflammatory bowel disease (IBD) and Parkinson’s disease (PD) are chronic disorders that have been suggested to share common pathophysiological processes. LRRK2 has been implicated as playing a role in both diseases. Exploring the genetic basis of the IBD-PD comorbidity through studying high-impact rare genetic variants can facilitate the identification of the novel shared genetic factors underlying this comorbidity.MethodsWe analyzed whole exomes from the BioMe BioBank and UK Biobank, and whole genomes from a cohort of 67 European patients diagnosed with both IBD and PD to examine the effects of LRRK2 missense variants on IBD, PD and their co-occurrence (IBD-PD). We performed optimized sequence kernel association test (SKAT-O) and network-based heterogeneity clustering (NHC) analyses using high-impact rare variants in the IBD-PD cohort to identify novel candidate genes, which we further prioritized by biological relatedness approaches. We conducted phenome-wide association studies (PheWAS) employing BioMe BioBank and UK Biobank whole exomes to estimate the genetic relevance of the 14 prioritized genes to IBD-PD.ResultsThe analysis of LRRK2 missense variants revealed significant associations of the G2019S and N2081D variants with IBD-PD in addition to several other variants as potential contributors to increased or decreased IBD-PD risk. SKAT-O identified two significant genes, LRRK2 and IL10RA, and NHC identified 6 significant gene clusters that are biologically relevant to IBD-PD. We observed prominent overlaps between the enriched pathways in the known IBD, PD, and candidate IBD-PD gene sets. Additionally, we detected significantly enriched pathways unique to the IBD-PD, including MAPK signaling, LPS/IL-1 mediated inhibition of RXR function, and NAD signaling. Fourteen final candidate IBD-PD genes were prioritized by biological relatedness methods. The biological importance scores estimated by protein–protein interaction networks and pathway and ontology enrichment analyses indicated the involvement of genes related to immunity, inflammation, and autophagy in IBD-PD. Additionally, PheWAS provided support for the associations of candidate genes with IBD and PD.ConclusionsOur study confirms and uncovers new LRRK2 associations in IBD-PD. The identification of novel inflammation and autophagy-related genes supports and expands previous findings related to IBD-PD pathogenesis, and underscores the significance of therapeutic interventions for reducing systemic inflammation.

Anticholinergic burden and the cognitive functions in elderly and senile patients with arterial hypertension

The aim of the study was to evaluate the effect of anticholinergic load (AHN) on cognitive functions (CF) in elderly and senile multimorbid patients with arterial hypertension (AH).Materials and methods. 330 patients aged 60 years and older with essential AH were included in the study (median age 79 [72; 84] years, 158 (51 %) of women). All the patients were underwent the assesment of CF using the Montreal Cognitive Assessment Scale (MoCA), Mini-Mental Status Scale (MMS), Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-cog), Trial Making Test (TMT), Digit Symbol Substitution Test (DSST), Verbal Association Test (literal (letter) and categorical (animal) associations), Boston Naming Test (BNT), Word-Color Interference Test, Stroop colorword conflict test. The anticholinergic load was determined using the anticholinergic load scale (Anticholinergic Cognitive Burden Scale, ACB).Results. Compared with patients who do not take anticholinergic drugs, multimorbid elderly and senile hypertensive patients with 2 or more points on the ACB scale had significantly lower final scores on the MoCA test (23 [21; 24.3] versus 24 [22; 25] points, respectively, p=0.042) and on MMSE (26 [24; 29] vs. 27.5 [25; 29] points, respectively, p=0.015), they spent statistically more time completing part B of the TMT test (217.5 [187.3; 246.3] vs. 204 [166.8; 247.3] seconds, respectively, p=0.038). The difference between the execution time of part B and part A of the TMT test in patients with 2 or more points on the ACB scale was statistically significantly greater than in patients with 0 points on this scale (141 [103.8; 168.5] versus 124 [83.8; 162] sec, respectively, p=0.034). Age, gender, education, and the structure of concomitant diseases did not differ between the groups.Conclusion. The results obtained indicate the adverse effect of аnticholinergic вurden on CF of multimorbid elderly and senile hypertensive patients and dictate the need to optimize pharmacotherapy in this category of patients.

The influence of depression and anxiety on cognition in people with multiple sclerosis: a cross-sectional analysis.

There are conflicting findings about the relationships between depression, anxiety, and cognitive dysfunction in people with multiple sclerosis (MS), and a paucity of research has examined the cumulative influence on cognition of depression plus anxiety. This study aimed to determine whether elevated symptoms of depression and anxiety alone or in combination are associated with worse cognition in people with MS. In this cross-sectional analysis, people with MS consecutively seen at a tertiary neuropsychiatry clinic completed the Hospital Anxiety and Depression Scale for symptoms of depression (HADS-D) and anxiety (HADS-A), and the Minimal Assessment of Cognitive Function in MS for cognitive indices. Accounting for covariates, regression models predicted cognitive indices from scores for HADS-D, HADS-A, and the interaction. Of 831 people with MS, 72% were female, mean age was 43.2years, and median Expanded Disability Status Scale score was 2.0. Depressive symptoms were independently predictive of lower verbal fluency (Controlled Oral Word Association Test, p < 0.01), verbal learning (California Verbal Learning Test-II (CVLT-II) total learning, p = 0.02), verbal delayed recall (CVLT-II delayed recall, p < 0.01), and processing speed (Symbol Digit Modalities Test, p < 0.01; three-second Paced Auditory Serial Addition Test (PASAT), p = 0.05; two-second PASAT, p = 0.01). Anxiety in people with depression predicted decreased visuospatial function (Judgment of Line Orientation, p = 0.05), verbal learning (p < 0.01), verbal delayed recall (p < 0.01), visuospatial recall (Brief Visuospatial Memory Test-Revised, p = 0.02), and executive function (Delis-Kaplan Executive Function System, p < 0.01). Anxiety alone was not independently predictive of cognition. In conclusion, depression, especially with comorbid anxiety, is associated with cognitive dysfunction in people with MS.

Association Analysis of Essential Tremor-Associated Genetic Variants in Sporadic Late-Onset Parkinson's Disease.

Parkinson's disease (PD) and Essential tremor (ET) are the two most common tremor diseases with recognized genetic pathogenesis. The overlapping clinical features suggest they may share genetic predispositions. Our previous study systematically investigated the association between rare coding variants in ET-associated genes and early-onset PD (EOPD), and found the suggestive association between teneurin transmembrane protein 4 (TENM4) and EOPD. In the current research, we explored the potential genetic interplay between ET-associated genetic loci/genes and sporadic late-onset PD (LOPD). We performed whole-genome sequencing in the 1962 sporadic LOPD cases and 1279 controls from mainland China. We first used logistic regression analysis to test the top 16 SNPs identified by the ET genome-wide association study for the association between ET and LOPD. Then we applied the optimized sequence kernel association testing to explore the rare variant burden of 33 ET-associated genes in this cohort. We did not observe a significant association between the included SNPs with LOPD. We also did not discover a significant burden of rare deleterious variants of ET-associated genes in association with LOPD risk. Our results do not support the role of ET-associated genetic loci and variants in LOPD. 1962 cases and 1279 controls were recruited to study the potential genetic interplay between ET-associated genetic loci/variants and sporadic LOPD.No significant association between the ET-associated SNPs and LOPD were observed.No significant burden of rare deleterious variants of ET-associated gene in LOPD risk were found.

A novel method for multiple phenotype association studies based on genotype and phenotype network.

Joint analysis of multiple correlated phenotypes for genome-wide association studies (GWAS) can identify and interpret pleiotropic loci which are essential to understand pleiotropy in diseases and complex traits. Meanwhile, constructing a network based on associations between phenotypes and genotypes provides a new insight to analyze multiple phenotypes, which can explore whether phenotypes and genotypes might be related to each other at a higher level of cellular and organismal organization. In this paper, we first develop a bipartite signed network by linking phenotypes and genotypes into a Genotype and Phenotype Network (GPN). The GPN can be constructed by a mixture of quantitative and qualitative phenotypes and is applicable to binary phenotypes with extremely unbalanced case-control ratios in large-scale biobank datasets. We then apply a powerful community detection method to partition phenotypes into disjoint network modules based on GPN. Finally, we jointly test the association between multiple phenotypes in a network module and a single nucleotide polymorphism (SNP). Simulations and analyses of 72 complex traits in the UK Biobank show that multiple phenotype association tests based on network modules detected by GPN are much more powerful than those without considering network modules. The newly proposed GPN provides a new insight to investigate the genetic architecture among different types of phenotypes. Multiple phenotypes association studies based on GPN are improved by incorporating the genetic information into the phenotype clustering. Notably, it might broaden the understanding of genetic architecture that exists between diagnoses, genes, and pleiotropy.

Exploring clinical specialists’ perspectives on the future role of AI: evaluating replacement perceptions, benefits, and drawbacks

Background of studyOver the past few decades, the utilization of Artificial Intelligence (AI) has surged in popularity, and its application in the medical field is witnessing a global increase. Nevertheless, the implementation of AI-based healthcare solutions has been slow in developing nations like Pakistan. This unique study aims to assess the opinion of clinical specialists on the future replacement of AI, its associated benefits, and its drawbacks in form southern region of Pakistan.Material and methodsA cross-sectional selective study was conducted from 140 clinical specialists (Surgery = 24, Pathology = 31, Radiology = 35, Gynecology = 35, Pediatric = 17) from the neglected southern Punjab region of Pakistan. The study was analyzed using χ2 - the test of association and the nexus between different factors was examined by multinomial logistic regression.ResultsOut of 140 respondents, 34 (24.3%) believed hospitals were ready for AI, while 81 (57.9%) disagreed. Additionally, 42(30.0%) were concerned about privacy violations, and 70(50%) feared AI could lead to unemployment. Specialists with less than 6 years of experience are more likely to embrace AI (p = 0.0327, OR = 3.184, 95% C.I; 0.262, 3.556) and those who firmly believe that AI knowledge will not replace their future tasks exhibit a lower likelihood of accepting AI (p = 0.015, OR = 0.235, 95% C.I: (0.073, 0.758). Clinical specialists who perceive AI as a technology that encompasses both drawbacks and benefits demonstrated a higher likelihood of accepting its adoption (p = 0.084, OR = 2.969, 95% C.I; 0.865, 5.187).ConclusionClinical specialists have embraced AI as the future of the medical field while acknowledging concerns about privacy and unemployment.

Association of obesity to reaction time and visual memory in schizophrenia

BackgroundBoth overweight and cognitive deficits are common among people with schizophrenia (SZ) and schizoaffective disorder. The results in earlier studies have been inconsistent on whether overweight is associated with cognitive deficits in psychotic disorders. AimsOur aim in this study was to detect possible associations between obesity and cognitive deficits among study participants with SZ and schizoaffective disorder. MethodsThe study sample included 5382 participants with a clinical diagnosis of SZ or schizoaffective disorder selected from the Finnish SUPER study. Obesity was measured both with body-mass index and waist circumference. The cognitive performance was evaluated with two tests from the Cambridge automated neuropsychological test battery: Reaction time was evaluated with the 5-choice serial reaction time task. Visual memory was evaluated with the paired associative learning test. The final analysis included a total sample of 4498 participants applicable for the analysis of the reaction time and 3967 participants for the analysis of the visual memory. ResultsObesity measured with body-mass index was associated with better performance in reaction time task among both female and male participants. Among male participants, overweight was associated with better performance in the visual memory test. The waist circumference was not associated with cognitive measures. ConclusionsThe results suggest that obesity in people with SZ or schizoaffective disorder might not be associated with cognitive deficits but instead with better cognitive performance. The results were opposite from earlier literature on the general population. More research is required to better understand whether the results might be partly caused by the differences in the etiology of obesity between the general population and people with SZ.

Assessing Implicit Theories in Sexual Offending Using Indirect Measures: Feasibility, Reliability, and Incremental Validity.

This study assessed psychometric qualities of indirect measures assessing Implicit Theories (ITs) of sexual offending: Implicit Association Task (IAT), Implicit Relational Assessment Procedure (IRAP), and Relational Responding Task (RRT). For comparison reasons, aggressive behavior was also assessed. In a male sample from the general population (N = 109), we assessed each measure's (a) feasibility (mean latency, error rate, passing criteria), (b) internal consistency, (c) convergent and discriminant validity, and (d) incremental and predictive validity. Results indicated that no indirect measure met all criteria. Although the IAT was reasonably feasible and reliable in measuring aggression, ITs could not be reliably assessed. The RRT was feasible and somewhat reliable in assessing ITs, whereas the IRAP showed limited feasibility, high task complexity, low reliability, and the presence of a method factor. No measure had incremental predictive validity over the use of self-report measures, although we note that the power to detect such associations was limited. As none of the indirect measures performed satisfactorily on the measured criteria, the use of these measures in clinical practice seems currently unwarranted to assess ITs.

Genetic polymorphisms associated with adverse pregnancy outcomes in nulliparas

Adverse pregnancy outcomes (APOs) affect a large proportion of pregnancies and represent an important cause of morbidity and mortality worldwide. Yet the pathophysiology of APOs is poorly understood, limiting our ability to prevent and treat these conditions. To search for genetic markers of maternal risk for four APOs, we performed multi-ancestry genome-wide association studies (GWAS) for pregnancy loss, gestational length, gestational diabetes, and preeclampsia. We clustered participants by their genetic ancestry and focused our analyses on three sub-cohorts with the largest sample sizes: European, African, and Admixed American. Association tests were carried out separately for each sub-cohort and then meta-analyzed together. Two novel loci were significantly associated with an increased risk of pregnancy loss: a cluster of SNPs located downstream of the TRMU gene (top SNP: rs142795512), and the SNP rs62021480 near RGMA. In the GWAS of gestational length we identified two new variants, rs2550487 and rs58548906 near WFDC1 and AC005052.1, respectively. Lastly, three new loci were significantly associated with gestational diabetes (top SNPs: rs72956265, rs10890563, rs79596863), located on or near ZBTB20, GUCY1A2, and RPL7P20, respectively. Fourteen loci previously correlated with preterm birth, gestational diabetes, and preeclampsia were found to be associated with these outcomes as well.