Convergent Evidence Research Articles

Casting a sustainable future: a study on dynamic prediction and influencing factors of economic resilience in fisheries management

Marine fisheries are a critical component of the marine economy. Examining the changes in the economic resilience of marine fisheries allows for identifying potential development risks and supports informed decision-making to optimize growth patterns and mitigate risks. This study applied the CRITIC-based combined weights model to calculate China’s Marine Fisheries Economic Resilience (MFER). It investigated the temporal and spatial evolution of MFER and analyzed the influencing factors using the Geographical Detector and a Two-way fixed-effects model. Furthermore, the future development trends of MFER were predicted using the Markov chain. The results show that the overall MFER in China’s coastal provinces increased steadily from 2001 to 2020. Second, MFER exhibits a clear pattern, with low-value regions improving and high-value areas shifting toward medium- and low-value provinces. Fourth, the trajectory of the MFER center is moving from north to south, with high-value regions expanding in the same direction. Fourth, factors such as EDL, TEC, SPE, and SYS positively impact MFER, while OPE has a negative effect. Finally, the results of the Markov chain indicate that the current development state of MFER is relatively stable, with evidence of club convergence. However, the probability of maintaining the current development level is gradually decreasing. Based on these findings, provide suggestions for the preservation of marine economic security.

Testing the Solow Hypothesis for Fiscal Convergence: a Dynamic Spatial Analysis

The study of regional fiscal convergence is a recent extension of the neoclassical growth theory. Various studies have shown the existence of fiscal convergence across countries or states in federally governed countries. This paper tests the growth theory on income and fiscal variables differently in a centrally ruled country. Therefore, we estimate spatial and non-spatial panel models from 2004 to 2022 for Türkiye. A general-to-specific methodology is applied for selecting an appropriate model to determine spatial interactions of the variables by using the panel data at the level of 81 Turkish provinces. The Ordinary Least Squares (OLS) estimation results from the non-spatial model partially validate the growth theory as the study does not find evidence of absolute convergence for government expenditures. The results, however, confirm the conditional convergence for all variables. The Maximum Likelihood (ML) method is applied for the estimation of the dynamic and static spatial panel models to explain their spatial interactions. The ML findings are consistent with the OLS results. Moreover, unlike direct and total effects, it is not possible to define indirect effects explaining spatial spillover effects in the short and long terms.

Evidence of altered monoamine oxidase B, an astroglia marker, in early psychosis and high-risk state.

A novel radiotracer, [11C]SL25.1188, targets monoamine oxidase-B (MAO-B) enzyme, found primarily in astrocytes, which metabolizes monoamines (including dopamine), particularly in subcortical regions. Altered astrocyte function in schizophrenia is supported by convergent evidence from post-mortem, genetic, transcriptomic, peripheral and preclinical findings. We aimed to test whether levels of MAO-B, an index of astrocyte function are low in the living brains of early psychosis and their high-risk states. Thirty-eight participants including antipsychotic-free/minimally exposed clinical participants with first-episode psychosis (FEP), clinical high-risk (CHR) individuals and healthy volunteers (HVs) underwent a 90-min positron emission tomography (PET) scan with [11C]SL25.1188, to measure MAO-B VT, an index of MAO-B concentration. Participants were excluded if tested positive on urine drug screen (except for cannabis). This study of 14 FEP (mean[SD] age, 25.7[5.7] years; 6 F), 7 CHR (mean[SD] age, 20.9[3.7] years; 4 F) and 17 HV (mean[SD] age, 31.2[13.9] years; 9 F) demonstrated significant group differences in regional MAO-B VT (F(2,37.42) = 4.56, p = 0.02, Cohen's f = 0.49), controlling for tobacco (F (1,37.42) = 5.37, p = 0.03) and cannabis use (F(1,37.42) = 5.11, p = 0.03) with significantly lower MAO-B VT in CHR compared to HV (Cohen's d = 0.99). We report a significant cannabis effect on MAO-B VT (F(1,39.19) = 12.57, p = 0.001, Cohen's f = 0.57), with a significant group-by-cannabis interaction (F(2,37.30) = 3.82, p = 0.03, Cohen's f = 0.45), indicating lower MAO-B VT in cannabis-using clinical groups. Lower MAO-B VT levels were more robust in striatal than cortical regions, in both clinical groups (F(12,46.84) = 2.08, p = 0.04, Cohen's f = 0.73) and in cannabis users (F(6,46.84) = 6.42, p < 0.001, Cohen's f = 0.91). Lower MAO-B concentration supports astrocyte dysfunction in cannabis-using CHR and FEP clinical populations. Lower MAO-B is consistent with replicated striatal dopamine elevation in psychosis, as well as astrocyte dysfunction in schizophrenia.

Large-scale exome sequencing identified 18 novel genes for neuroticism in 394,005 UK-based individuals.

Existing genetic studies of neuroticism have been largely limited to common variants. Here we performed a large-scale exome analysis of white British individuals from UK Biobank, revealing the role of coding variants in neuroticism. For rare variants, collapsing analysis uncovered 14 neuroticism-associated genes. Among these, 12 (PTPRE, BCL10, TRIM32, ANKRD12, ADGRB2, MON2, HIF1A, ITGB2, STK39, CAPNS2, OGFOD1 and KDM4B) were novel, and the remaining (MADD and TRPC4AP) showed convergent evidence with common variants. Heritability of rare coding variants was estimated to be up to 7.3% for neuroticism. For common variants, we identified 78 significant associations, implicating 6 unreported genes. We subsequently replicated these variants using meta-analysis across other four ancestries from UK Biobank and summary data from 23andMe sample. Furthermore, these variants had widespread impacts on neuropsychiatric disorders, cognitive abilities and brain structure. Our findings deepen the understanding of neuroticism's genetic architecture and provide potential targets for future mechanistic research.

Small business in structural shifts in Ukrainian economy during 2012-2022 in the context of solving the problems of economic development

The article is devoted to testing the author’s methodology for assessing the contribution of structural changes (distribution of the employees’ total number between large, medium and small enterprises) to the processes of socio-economic development in Ukraine. For this purpose, the general trends in the dynamics of the scale and efficiency of the sector of Ukrainian non-financial enterprises and the specifics of such trends for enterprises with different scales of economic activity are studied for the retrospective period 2012-2022. Due to the fundamental differences in the factors of economic dynamics, the years of relatively stable political and epidemiological situation are studied separately from the years of significant political, military-political and epidemiological disturbances. Using the additive-multiplicative model of the value added, created by Ukrainian enterprises dependence on the number of employees, the proportions of their distribution among large, medium and small enterprises and labor productivity (value added per capita) and the method of sequential substitutions, the author conducts a factor analysis of the dynamics of value added created by Ukrainian enterprises in the retrospective period. Evidence of significant convergence of the economic efficiency level of small and large enterprises during the retrospective period and the leading role of small enterprises in improving the efficiency of economic activity in Ukraine and ensuring the resilience of the economy to negative external and internal disturbances is obtained.

Evidence for convergence of distributed cortical processing in band-like functional zones in human entorhinal cortex.

The wide array of cognitive functions associated with the hippocampus is supported through interactions with the cerebral cortex. However, most of the direct cortical input to the hippocampus originates in the entorhinal cortex, forming the hippocampal-entorhinal system. In humans, the role of the entorhinal cortex in mediating hippocampal-cortical interactions remains unknown. In this study, we used precision neuroimaging to examine the distributed cortical anatomy associated with the human hippocampal-entorhinal system. Consistent with animal anatomy, our results associate different subregions of the entorhinal cortex with different parts of the hippocampus long axis. Furthermore, we find that the entorhinal cortex comprises three band-like zones that are associated with functionally distinct cortical networks. Importantly, the entorhinal cortex bands traverse the proposed human homologs of rodent lateral and medial entorhinal cortices. Finally, we show that the entorhinal cortex is a major convergence area of distributed cortical processing and that the topography of cortical networks associated with the anterior medial temporal lobe mirrors the macroscale structure of high-order cortical processing.

Changing Geographies of Segregation in the US Care Sector: An Intersectional View on Low-Wage Care Workers

Recent literature highlights longstanding structural inequalities in the US care economy, particularly along gender, racial, and ethnic lines. However, limited attention has been paid to the role of geography in structuring these disparities. This paper addresses this gap by descriptively analyzing of occupational segregation in the US low-wage care sector across commuting zones from 1980 to 2020. Our findings show that women are still more likely than men to work in low-wage care occupations. Moreover, local racial and ethnic composition plays a key role in determining who performs low-wage care work, with racialized women persistently overrepresented in low-wage care employment both nationally and regionally. While there is significant regional variation in occupational segregation, there is evidence of convergence in recent decades. Finally, using group-based trajectory modeling, we identify distinct regional trajectories in the evolution of occupational segregation in the low-wage care sector, demonstrating that national averages mask underlying regional trends.

An overview of the pathophysiology of agitation in Alzheimer's dementia with a focus on neurotransmitters and circuits.

Alzheimer's dementia (AD) is a progressive, neurodegenerative disease often accompanied by neuropsychiatric symptoms that profoundly impact both patients and caregivers. Agitation is among the most prevalent and distressing of these symptoms and often requires treatment. Appropriate therapeutic interventions depend on understanding the biological basis of agitation and how it may be affected by treatment. This narrative review discusses a proposed pathophysiology of agitation in Alzheimer's dementia based on convergent evidence across research approaches. Available data indicate that agitation in Alzheimer's dementia is associated with an imbalance of activity between key prefrontal and subcortical brain regions. The monoamine neurotransmitter systems serve as key modulators of activity within these brain regions and circuits and are rendered abnormal in AD. Patients with AD who exhibited agitation symptoms during life have alterations in neurotransmitter nuclei and related systems when the brain is examined at autopsy. The authors present a model of agitation in Alzheimer's dementia in which noradrenergic hyperactivity along with serotonergic deficits and dysregulated striatal dopamine release contribute to agitated and aggressive behaviors.

Шкала родительского стресса: адаптация на русскоязычной выборке матерей школьников

&lt;p style="text-align: justify;"&gt;&lt;strong&gt;Objective. &lt;/strong&gt;Adaptation of the Parental Stress Scale by J. Berry and V. Jones on a sample of mothers of Russian schoolchildren &amp;ndash; first and fourth grade students of elementary schools in Nizhny Novgorod and the Nizhny Novgorod region. &lt;br&gt;&lt;strong&gt;Background. &lt;/strong&gt;Modern parenting research highlights the complex nature of parenting experiences, the diversity of parental practices, the changes associated with the child's upbringing and the dynamics of the family system, and the combination of both positive and negative emotions in parenting. However, there is a noticeable shortage of tools in the Russian-language literature to measure both parental satisfaction and parental stress. &lt;br&gt;&lt;strong&gt;Study design. &lt;/strong&gt;The study was conducted using an online survey within the &amp;ldquo;Longitudinal study of factors of school failure&amp;rdquo;, implemented in Nizhny Novgorod and the Nizhny Novgorod region. &lt;strong&gt;Participants. &lt;/strong&gt;The study included a sample of 900 mothers of fourth grade and 1120 mothers of the first grade school students. &lt;strong&gt;Measurements.&lt;/strong&gt; Exploratory and confirmatory factor analysis and McDonald's Omega coefficients were used for psychometric data analysis. The PERMA Profiler questionnaire and correlation analysis were used to assess validity based on convergent and discriminant evidence. The data was analyzed in the Jamovi 2022 and R programs. &lt;br&gt;&lt;strong&gt;Results. &lt;/strong&gt;Factor analyses of the internal structure suggest two factors, including 8 items each. The subscales &amp;ldquo;Parental stress&amp;rdquo; and &amp;ldquo;Parental satisfaction&amp;rdquo; demonstrate a high level of internal consistency. The assessment of validity based on the convergent and discriminant evidence confirms the reliability and validity of the instrument. &lt;br&gt;&lt;strong&gt;Conclusions. &lt;/strong&gt;The scale demonstrates good psychometric properties and can be used for parenting research, as well as in applied projects to improve parental competence and emotional support for parents.&lt;/p&gt;

Divergent and Convergent TMEM106B Pathology in Murine Models of Neurodegeneration and Human Disease.

TMEM106B is a lysosomal/late endosome protein that is a potent genetic modifier of multiple neurodegenerative diseases as well as general aging. Recently, TMEM106B was shown to form insoluble aggregates in postmortem human brain tissue, drawing attention to TMEM106B pathology and the potential role of TMEM106B aggregation in disease. In the context of neurodegenerative diseases, TMEM106B has been studied in vivo using animal models of neurodegeneration, but these studies rely on overexpression or knockdown approaches. To date, endogenous TMEM106B pathology and its relationship to known canonical pathology in animal models has not been reported. Here, we analyze histological patterns of TMEM106B in murine models of C9ORF72 -related amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD), SOD1-related ALS, and tauopathy and compare these to postmortem human tissue from patients with C9-ALS/FTD, Alzheimer's disease (AD), and AD with limbic-predominant age-related TDP-43 encephalopathy (AD/LATE). We show that there are significant differences between TMEM106B pathology in mouse models and human patient tissue. Importantly, we also identified convergent evidence from both murine models and human patients that links TMEM106B pathology to TDP-43 nuclear clearance specifically in C9-ALS. Similarly, we find a relationship at the cellular level between TMEM106B pathology and phosphorylated Tau burden in Alzheimer's disease. By characterizing endogenous TMEM106B pathology in both mice and human postmortem tissue, our work reveals considerations that must be taken into account when analyzing data from in vivo mouse studies and elucidates new insights supporting the involvement of TMEM106B in the pathogenesis and progression of multiple neurodegenerative diseases.

Spectral Pseudorandomness and the Road to Improved Clique Number Bounds for Paley Graphs

We study subgraphs of Paley graphs of prime order p induced on the sets of vertices extending a given independent set of size a to a larger independent set. Using a sufficient condition due to Kunisky (2023), we show that estimates on a new family of necklace character sums would imply that, as p → ∞ , the empirical spectral distributions of the adjacency matrices of any sequence of such subgraphs have the same weak limit (after rescaling) as those of subgraphs induced on a random set including each vertex independently with probability 2 − a , namely, a Kesten-McKay law with parameter 2 a . We prove the necessary estimates for a = 1, obtaining in the process an alternate proof of a character sum equidistribution result of Xi (2022), and provide numerical evidence for this weak convergence for a ≥ 2 . We also conjecture that the minimum eigenvalue of any such sequence converges (after rescaling) to the left edge of the corresponding Kesten-McKay law, and provide numerical evidence for this convergence. Finally, we show that, once a ≥ 3 , this (conjectural) convergence of the minimum eigenvalue would imply bounds on the clique number of the Paley graph improving on the current state of the art due to Hanson and Petridis (2021), and that this convergence for all a ≥ 1 would imply that the clique number is o ( p ) .

Quantifying convergence and consistency.

The reproducibility crisis highlights several unresolved issues in science, including the need to develop measures that gauge both the consistency and convergence of data sets. While existing meta-analytic methods quantify the consistency of evidence, they do not quantify its convergence: the extent to which different types of empirical methods have provided evidence to support a hypothesis. To address this gap in meta-analysis, we and colleagues developed a summary metric-the cumulative evidence index (CEI)-which uses Bayesian statistics to quantify the degree of both consistency and convergence of evidence regarding causal hypotheses between two phenomena. Here, we outline the CEI's underlying model, which quantifies the extent to which studies of four types-positive intervention, negative intervention, positive non-intervention and negative non-intervention-lend credence to any of three types of causal relations: excitatory, inhibitory or no-connection. Along with p-values and other measures, the CEI can provide a more holistic perspective on a set of evidence by quantitatively expressing epistemic principles that scientists regularly employ qualitatively. The CEI can thus address the reproducibility crisis by formally demonstrating how convergent evidence across multiple study types can yield progress toward scientific consensus, even when an individual type of study fails to yield reproducible results.

Glutamate concentration of medial prefrontal cortex is inversely associated with addictive behaviors: a translational study

In both preclinical and clinical settings, dysregulated frontostriatal circuits have been identified as the underlying neural substrates of compulsive seeking/taking behaviors manifested in substance use disorders and behavioral addictions including internet gaming disorder (IGD). However, the neurochemical substrates for these disorders remain elusive. The lack of comprehensive cognitive assessments in animal models has hampered our understanding of neural plasticity in addiction from these models. In this study, combining data from a rat model of compulsive taking/seeking and human participants with various levels of IGD severity, we investigated the relationship between regional glutamate (Glu) concentration and addictive behaviors. We found that Glu levels were significantly lower in the prelimbic cortex (PrL) of rats after 20-days of methamphetamine self-administration (SA), compared to controls. Glu concentration after a punishment phase negatively correlated with acute drug-seeking behavior. In addition, changes in Glu levels from a drug naïve state to compulsive drug taking patterns negatively correlated with drug-seeking during both acute and prolonged abstinence. The human data revealed a significant negative correlation between Glu concentration in the dorsal anterior cingulate cortex (dACC), the human PrL counterpart, and symptoms of IGD. Interestingly, there was a positive correlation between Glu levels in the dACC and self-control, as well as mindful awareness. Further analysis revealed that the dACC Glu concentration mediated the relationship between self-control/mindful awareness and IGD symptoms. These results provide convergent evidence for a protective role of dACC/PrL in addiction, suggesting interventions to enhance dACC glutamatergic functions as a potential strategy for addiction prevention and treatment.

Heartfelt choices: The influence of cardiac phase on free-choice actions.

The influence of cardiac phases on cognitive and sensorimotor functions is noteworthy. Specifically, during systole, as opposed to diastole, there is an observed enhancement in tasks demanding the suppression of instructed responses. This suggests that systole contributes to inhibitory control in motor functions. However, the extent to which systolic inhibition is significant in volitional free-choice actions, such as choosing to execute or refrain from a cue-initiated response, remains to be clarified. To fill this gap in the current literature, the purpose of this study was to test whether during the systole phase, compared with the diastole phase, the tendency to enact volitional actions decreased due to the systolic inhibitory effect. We used a modified version of the Go/No-Go task with an added condition for volitional free-choice actions, where participants could decide whether to respond or not, to test whether systolic inhibition could affect the volitional decision to act. The results showed that participants' responses were less frequent in systole than in diastole in the volitional action condition. Then, to test the robustness of the cardiac effect on volitional actions, we used two established manipulations: the Straw Breathing Manipulation and the Cold Pressor Test, which were able to induce anxiety and increase the heart rate, respectively. Results showed that the systole/diastole difference in the number of volitional action trials in which participants decided to respond tended to remain the same despite all manipulations. Overall, our results provide convergent evidence for the effect of the heart on the decision to act, an effect that appears independent of manipulations of both the physiological and psychological state of the individual.

Evolution and Plasticity of Gene Expression Under Progressive Warming in Drosophila subobscura.

Understanding the molecular mechanisms of thermal adaptation is crucial to predict the impacts of global warming. However, there is still a lack of research on the effects of rising temperatures over time and of studies involving different populations from the same species. The present study focuses on these two aspects, which are of great importance in understanding how organisms cope and adapt to ongoing changes in their environment. This study investigates the impact of global warming on the gene expression patterns of Drosophila subobscura populations from two different latitudinal locations after 23 generations of evolution. Our results indicate that evolutionary changes depend on the genetic background of the populations, with different starting points for thermal evolution, and that high-latitude populations show more pronounced evolutionary changes, with some evidence of convergence towards low-latitude populations. We found an interplay between plasticity and selection, with the high-latitude population showing fewer initial plastic genes and lower levels of adaptive plasticity, but a greater magnitude of change in both plastic and selective responses during evolution under warming conditions compared with its low-latitude counterpart. A substantial proportion of the transcriptome was observed to be evolving, despite the lack of observable response at higher-order phenotypic traits. The interplay between plasticity and selection may prove to be an essential component in shaping species' evolutionary responses to climate change. Furthermore, the value of conducting studies on multiple populations of the same species is emphasised, given the identification of differences between populations with different backgrounds in several contexts.

A dopaminergic basis of behavioral control.

Both goal-directed and automatic processes shape human behavior, but these processes often conflict. Behavioral control is the decision about which process guides behavior. Despite the importance of behavioral control for adaptive decision-making, its neural mechanisms remain unclear. Critically, it is unknown if there are mechanisms for behavioral control that are distinct from those supporting the formation of goal-relevant knowledge. We performed deep phenotyping of individual dopamine system function by combining multiple PET scans, fMRI, and dopaminergic drug administration in a within-subject, double-blind, placebo-controlled design. Subjects performed a rule-based response time task, with goal-directed and automatic decision-making operationalized as model-based and model-free influences on behavior. We found a double dissociation between two aspects of ventral striatal dopamine physiology: D2/3 receptor availability and dopamine synthesis capacity. Convergent and causal evidence indicated that D2/3 receptors regulate behavioral control by enhancing model-based and blunting model-free influences on behavior but do not affect model-based knowledge formation. In contrast, dopamine synthesis capacity was linked to the formation of model-based knowledge but not behavioral control. D2/3 receptors also modulated frontostriatal functional connectivity, suggesting they regulate behavioral control by gating prefrontal inputs to the striatum. These results identify central mechanisms underlying individual and state differences in behavioral control and point to striatal D2/3 receptors as targets for interventions for improving goal-directed behavior.

Auditory processing up to cortex is maintained during sleep spindles

Abstract Sleep spindles are transient 11–16 Hz brain oscillations generated by thalamocortical circuits. Their role in memory consolidation is well established, but how they play a role in sleep continuity and protection of memory consolidation against interference is unclear. One theory posits that spindles or a neural refractory period following their offset act as a gating mechanism, blocking sensory information en route to the cortex at the level of the thalamus. An alternative model posits that spindles do not participate in the suppression of neural responses to sound, although they can be produced in response to sound. We present evidence from three experiments using electroencephalography and magnetoencephalography in humans that examine different evoked responses in the presence of and following sleep spindles. The results provide convergent empirical evidence suggesting that auditory processing up to cortex is maintained during sleep spindles, and their refractory periods.

Guilt, shame, and/or both? Further validation of the White Racial Affect Scale.

In this study we assessed the construct validity of the recently published White Racial Affect Scale (Grzanka et al., 2020). Specifically, we assessed the convergent, criterion-related, and incremental evidence for construct validity of the White guilt, White shame, and White defensiveness (called "White negation" in the original article) factors. We used a video stimulus to trigger state guilt and shame in participants as part of the construct validity investigation. White adults in the United States signed up for the study online (N = 262) and watched a 5-min video stimulus and completed questionnaires before and after the video. Results of this study replicated many of the findings from the original White Racial Affect Scale validation study (Grzanka et al., 2020). We found strong evidence of construct validity for the White guilt and White defensiveness factors and mixed evidence for the White shame factor. We discuss directions for future research and implications for potential interventions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Undergraduate Engineering Mental Health Help‐Seeking Instrument (UE‐MH‐HSI): Development and validity evidence

AbstractBackgroundUndergraduate engineering students experiencing distress are less likely than peers to ask for professional help. A population‐specific instrument to facilitate the identification of factors that influence mental healthcare utilization could guide development and testing of interventions to increase help seeking.PurposeWe used mixed methods guided by the Integrated Behavioral Model (IBM) to develop and evaluate the Undergraduate Engineering Mental Health Help‐Seeking Instrument (UE‐MH‐HSI).MethodFirst, we adapted existing measures of mental health help‐seeking intention and mechanisms (i.e., attitudes, perceived norm: injunctive, perceived norm: descriptive, personal agency: autonomy, personal agency: capacity). Second, we coded qualitative interviews (N = 33) to create population‐specific mental health help‐seeking belief measures (i.e., outcome beliefs, experiential beliefs, beliefs about others' expectations, beliefs about others' behavior, beliefs about barriers and facilitators). Third, we tested the psychometric properties using data from 596 undergraduate engineering students at a historically White, research‐focused institution in southern United States.ResultsPsychometric analyses indicated that (1) help‐seeking mechanism and intention measures demonstrated unidimensionality, internal consistency, construct replicability, and sufficient variability; (2) mechanism measures demonstrated criterion evidence of validity; and (3) most items within the belief measures demonstrated sufficient variability and convergent evidence of validity.ConclusionsThe UE‐MH‐HSI is an evidence‐based tool for investigating mental health help‐seeking factors and their relationship to help‐seeking behavior, well‐being, academic success, and engineering identity formation. Guidelines for use are provided.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance. Genes encoding ion channels show strong association with multiple epilepsy subtypes, including epileptic encephalopathies, generalized and focal epilepsies, while most other gene discoveries are subtype-specific, highlighting distinct genetic contributions to different epilepsies. Combining results from rare single nucleotide/short indel-, copy number-, and common variants, we offer an expanded view of the genetic architecture of epilepsy, with growing evidence of convergence among different genetic risk loci on the same genes. Top candidate genes are enriched for roles in synaptic transmission and neuronal excitability, particularly postnatally and in the neocortex. We also identify shared rare variant risk between epilepsy and other neurodevelopmental disorders. Our data can be accessed via an interactive browser, hopefully facilitating diagnostic efforts and accelerating the development of follow-up studies.