Genome-wide association study of borderline personality disorder reveals genetic overlap with the bipolar disorder, schizophrenia and major depression

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of Bipolar Disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was: (i) to detect genes and gene-sets involved in BOR; and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, Major Depression (MDD) and Schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests,and gene-set-analyses were performed in 998 BOR patients and 1,545 controls. LD score regression was used to detect genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Genebased analysis yielded two significant genes: DPYD (p=4.42x10-7) and PKP4 (p=8.67x10-7); and gene-set-analysis yielded a significant finding for exocytosis (GO:0006887, pFDR=0.019). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [p=2.99x10-3]), SCZ (rg=0.34 [p=4.37x10-5]), and MDD (rg=0.57 [p=1.04x10-3]). Our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies

Genome-wide Association Study of Borderline Personality Disorder Reveals Genetic Overlap with Bipolar Disorder, Major Depression and Schizophrenia

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case–control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10−7) and PKP4 (P=8.67 × 10−7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [P=2.99 × 10−3]), SCZ (rg=0.34 [P=4.37 × 10−5]) and MDD (rg=0.57 [P=1.04 × 10−3]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

The Crowdsourced Replication Initiative: Investigating Immigration and Social Policy Preferences. Executive Report.

In an era of mass migration, social scientists, populist parties and social movements raise concerns over the future of immigration-destination societies. What impacts does this have on policy and social solidarity? Comparative cross-national research, relying mostly on secondary data, has findings in different directions. There is a threat of selective model reporting and lack of replicability. The heterogeneity of countries obscures attempts to clearly define data-generating models. P-hacking and HARKing lurk among standard research practices in this area.This project employs crowdsourcing to address these issues. It draws on replication, deliberation, meta-analysis and harnessing the power of many minds at once. The Crowdsourced Replication Initiative carries two main goals, (a) to better investigate the linkage between immigration and social policy preferences across countries, and (b) to develop crowdsourcing as a social science method. The Executive Report provides short reviews of the area of social policy preferences and immigration, and the methods and impetus behind crowdsourcing plus a description of the entire project. Three main areas of findings will appear in three papers, that are registered as PAPs or in process

Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty

This study explores how researchers’ analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers’ expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each team’s workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers’ results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings

Individualismus, komplexe Identität, Menschenrechte und Solidarität. Eine Re-Interpretation der Solidaritätstheorie Émile Durkheims wider den Atomismusvorwurf

Die Allgemeine Erklärung der Menschenrechte der Vereinten Nationen von 1948 – aber auch frühere Menschenrechtserklärungen – sah sich stets Kritik aus unterschiedlichen Richtungen ausgesetzt. Diese beinhaltete sowohl Einwände z.B. von religiöser, feministischer und kulturrelativistischer Seite als auch Bedenken von Behindertenverbänden. Eine besonders markante Kritik ist jedoch die des Atomismus, welche in unterschiedlichen Variationen mindestens seit Hegel immer wieder vorgebracht wird. Sie besagt, Menschenrechte seien individualistische Rechte mit solidaritätszersetzendem Charakter. Begründet wird dies damit, dass die Betonung des Individuums als Träger unveräußerlicher Rechte hier notwendigerweise den Egoismus des Einzelnen befördere und moralischen Partikularismus zur Folge hätte. Die vorliegende Arbeit begegnet diesem Vorwurf, indem sie aufzeigt, dass es dem ihm zugrundeliegende Solidaritätsbegriff an Komplexität mangelt um das Phänomen adäquat zu beschreiben. Eben jener Mangel ist es jedoch, welcher den Atomismusvorwurf erst ermöglicht, da diejenige Solidarität, welche hier beschrieben wird, notwendigerweise an der Komplexität moderner Gesellschaften scheitern muss. Der Solidaritätsbegriff, welcher im Kontrast dazu im vorliegenden Text vorgestellt wird, überwindet dieses Problem. Er basiert zu großen Teilen auf der Theorie Émile Durkheims, geht aber auch darüber hinaus. Mit Hilfe von Durkheims Konzepten der mechanischen und organischen Solidarität im Zusammenhang mit der – der Menschenrechtsidee nahestehenden – Idee des Kult des Individuums wird gezeigt, dass Menschenrechte keineswegs schädlich für die Solidarität in modernen Gesellschaften sind. Vielmehr fördern sie bereits bestehende Solidaritäten und erzeugen zudem neue Formen menschenrechtlicher Solidarität.The Universal Declaration of Human Rights, declared by the United Nations in 1948 but also earlier Human Rights declarations, have always been the target of criticism. Objections to Human Rights include religious criticism, feminist reproval, and cultural relativistic arguments, as well as concerns expressed by associations supporting the disabled. One prominent objection refers to Atomism, which has been a central argument since Hegel introduced it. The objection of Atomism claims that Human Rights are corroding social solidarity, due to a disproportional focus on the individual as bearer of inalienable rights. Thus, Human Rights are said to promote egotistic individuals, along with moral particularism. In the present text, the Atomist objection is rendered irrelevant, as its definition of social solidarity lacks the complexity to describe contemporary societies. Thus, Atomism can be aptly criticized, as the social solidarity it objects to no longer applies. Instead, the concept of social solidarity is redefined by building on the theory of Émile Durkheim. In referring to Durkheim’s ideas, of mechanic solidarity and organic solidarity, as well as the concept of the Cult of the Individual, considered as closely related to Human Rights, it becomes evident that Human Rights do not harm solidarity in contemporary societies after all. Rather, Human Rights promote existing solidarities and, moreover, create new forms of solidarity

Psychometric Properties of the Chinese Version of the Brief Borderline Symptom List in Undergraduate Students and Clinical Patients

The brief version of the Borderline Symptom List (BSL-23) is a self-rated scale developed from the initial 95-item version of Borderline Symptom List (BSL-95). The current study aimed to evaluate the psychometric properties of the Chinese version of the BSL-23. A total of 570 undergraduate students and 323 clinical patients completed the BSL-23, the borderline subscale of the Personality Diagnostic Questionnaire (PDQ-4+), the Center for Epidemiologic Studies Depression Scale (CES-D), the Barratt Impulsiveness Scale, 11th version (BIS-11), the Childhood Trauma Questionnaire (CTQ) and the Attachment Style Questionnaire (ASQ). A Confirmatory Factor Analysis (CFA) was conducted to test the one-factor structure of the BSL-23. Cronbach’s alpha, Omega coefficient, Split-Half coefficient, Mean Inter-Item Correlation (MIC) and test-retest reliability were also measured. The correlations between the BSL-23 and other psychological variables were used to assess criterion-related validity and convergent validity. Participants who scored ≥ 5 on the borderline subscale of the PDQ-4+ were placed into the borderline personality disorder (BPD) screening-positive group, while the others were placed into the screening-negative group. Independent sample t-tests were performed to examine the differences in BSL-23 scores between the BPD screening-positive group and the BPD screening-negative group. The CFA results supported the one-factor structure of the BSL-23 in both samples. The internal consistency was high both in the undergraduate sample (Cronbach’s α = 0.93, Omega = 0.95, Split-Half coefficient = 0.89, MIC = 0.38) and the clinical sample (Cronbach’s α = 0.97, Omega = 0.97, Split-Half coefficient = 0.96, MIC = 0.56). The test-retest reliability within 2 weeks was 0.62. The BSL-23 displayed moderate to high correlations with the PDQ-4+-Borderline subscale, the CES-D, the BIS-11, the CTQ and the ASQ (r = 0.35 – 0.70). In addition, the BSL-23 discriminated between the BPD screening-positive and the BPD screening-negative participants, and also between the patient sample and undergraduate sample. In conclusion, the Chinese version of the BSL-23 has satisfactory psychometric properties to assess BPD symptoms

Significance of differences in general attitudes toward secondary use and willingness to support secondary use by self-perception as physician-scientist and purely clinical physician.

Significance of differences in general attitudes toward secondary use and willingness to support secondary use by self-perception as physician-scientist and purely clinical physician.</p

Conditions for providing patients’ clinical data available for medical studies and significance of differences in proportions by self-perception as physician-scientist or physician (n = 382).

Conditions for providing patients’ clinical data available for medical studies and significance of differences in proportions by self-perception as physician-scientist or physician (n = 382).</p