Genome-wide association study of borderline personality disorder identifies 11 loci and highlights shared risk with mental and somatic disorders.

We conducted the largest genome-wide meta-analysis of borderline personality disorder (BPD) to date, with a discovery sample of 12,339 cases and 1,041,717 controls, and a replication study of 685 cases and 107,750 controls (all participants of European ancestry). We identified 11 independent associated genomic loci, and nine risk genes in the gene-based analysis. We observed a single-nucleotide polymorphism (SNP) heritability of 17.

Robust inference and widespread genetic correlates from a large-scale genetic association study of human personality.

Personality traits describe stable differences in how individuals think, feel, and behave and how they interact with and experience their social and physical environments. We assemble data from 46 cohorts including 611K-1.14M participants with European-like and African-like genomes for genome-wide association studies (GWAS) of the Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism, and openness to experience), and data from 51K participants for within-family GWAS.

Prioritizing Parkinson's disease risk genes in genome-wide association loci.

Many drug targets in ongoing Parkinson's disease (PD) clinical trials have strong genetic links. While genome-wide association studies (GWAS) nominate regions associated with disease, pinpointing causal genes is challenging. Our aim was to prioritize additional druggable genes underlying PD GWAS signals.

Prioritizing Parkinson's disease risk genes in genome-wide association loci.

Recent advancements in Parkinson's disease (PD) drug development have been significantly driven by genetic research. Importantly, drugs supported by genetic evidence are more likely to be approved. While genome-wide association studies (GWAS) are a powerful tool to nominate genomic regions associated with certain traits or diseases, pinpointing the causal biologically relevant gene is often challenging.

DNAJC13 influences responses of the extended reward system to conditioned stimuli: a genome-wide association study.

Reward system dysfunction is implicated in the pathogenesis of major psychiatric disorders. We conducted a genome-wide association study (GWAS) to identify genes that influence activation strength of brain regions within the extended reward system in humans. A homogeneous sample of 214 participants was genotyped and underwent functional magnetic resonance imaging (fMRI).

Identifying drug targets for schizophrenia through gene prioritization.

Background: Schizophrenia genome-wide association studies (GWASes) have identified >250 significant loci and prioritized >100 disease-related genes. However, gene prioritization efforts have mostly been restricted to locus-based methods that ignore information from the rest of the genome.

Methods: To more accurately characterize genes involved in schizophrenia etiology, we applied a combination of highly-predictive tools to a published GWAS of 67,390 schizophrenia cases and 94,015 controls.

Polygenic risk for Alzheimer's disease is associated with neuroaxonal damage before onset of clinical symptoms.

Introduction: Establishing valid diagnostic strategies is a precondition for successful therapeutic intervention in Alzheimer's disease (AD).

Methods: One hundred forty-four healthy 75-year-old participants from the Vienna-Transdanube-Aging longitudinal cohort study were tested for neuroaxonal damage by single molecular array (Simoa) plasma neurofilament light chain (NfL) levels at baseline, 30, 60, and 90 months, and onset of AD dementia. Individual risk for sporadic AD was estimated by continuous shrinkage polygenic risk score (PRS-CS, genome-wide association study).

Evidence for a shared genetic contribution to loneliness and borderline personality disorder.

Loneliness, influenced by genetic and environmental factors such as childhood maltreatment, is one aspect of interpersonal dysfunction in Borderline Personality Disorder (BPD). Numerous studies link loneliness and BPD and twin studies indicate a genetic contribution to this association. The aim of our study was to investigate whether genetic predisposition for loneliness and BPD risk overlap and whether genetic risk for loneliness contributes to higher loneliness reported by BPD patients, using genome-wide genotype data.

Polygenetic risk scores and phenotypic constellations of obsessive-compulsive disorder in clozapine-treated schizophrenia.

Obsessive-compulsive symptoms (OCS) are frequently observed in individuals with schizophrenia (SCZ) treated with clozapine (CLZ). This study aimed to analyze prevalence of OCS and obsessive-compulsive disorder (OCD) in this subgroup and find possible correlations with different phenotypes. Additionally, this is the first study to examine polygenetic risk scores (PRS) in individuals with SCZ and OCS.

GWAS quality score for evaluating associated regions in GWAS analyses.

Motivation: The number of significantly associated regions reported in genome-wide association studies (GWAS) for polygenic traits typically increases with sample size. A traditional tool for quality control and identification of significant regions has been a visual inspection of how significant and correlated genetic variants cluster within a region. However, while inspecting hundreds of regions, this subjective method can misattribute significance to some loci or neglect others that are significant.

How alcohol makes the epigenetic clock tick faster and the clock reversing effect of abstinence.

This study investigated the recently reported association between alcohol dependence and accelerated ageing and the potential effects of abstinence and relapse on DNA methylation status using Levine's epigenetic clock to estimate DNA methylation age in two independent cohorts. The first sample comprised 88 (15 female) detoxified patients with alcohol use disorder (AUD) and 32 (5 female) healthy control (CON) subjects (NCT02615977), and the second included 69 (10 female) AUD patients that were followed up for 12 months with respect to relapse (n = 38, 4 female) and abstinence (n = 31, 6 female) (NCT01679145). To account for the different aspects of ageing captured by various clocks, we performed additional analyses of the first-generation Horvath clock and next-generation Zhang clock.

Corrigendum: Potential genetic overlap between insomnia and sleep symptoms in major depressive disorder: A polygenic risk score analysis.

[This corrects the article DOI: 10.3389/fpsyt.2021.

Borderline personality disorder and the big five: molecular genetic analyses indicate shared genetic architecture with neuroticism and openness.

Both environmental (e.g. interpersonal traumatization during childhood and adolescence) and genetic factors may contribute to the development of Borderline Personality Disorder (BPD).

Potential Genetic Overlap Between Insomnia and Sleep Symptoms in Major Depressive Disorder: A Polygenic Risk Score Analysis.

The prevalence of insomnia and hypersomnia in depressed individuals is substantially higher than that found in the general population. Unfortunately, these concurrent sleep problems can have profound effects on the disease course. Although the full biology of sleep remains to be elucidated, a recent genome-wide association (GWAS) of insomnia, and other sleep traits in over 1 million individuals was recently published and provides many promising hits for genetics of insomnia in a population-based sample.

The Genetic Architecture of Depression in Individuals of East Asian Ancestry: A Genome-Wide Association Study.

Importance: Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations.

Objective: To investigate the genetics of depression among individuals of East Asian and European descent living in different geographic locations, and with different outcome definitions for depression.

Polygenic risk for schizophrenia and schizotypal traits in non-clinical subjects.

Background: Schizotypy is a putative risk phenotype for psychosis liability, but the overlap of its genetic architecture with schizophrenia is poorly understood.

Methods: We tested the hypothesis that dimensions of schizotypy (assessed with the SPQ-B) are associated with a polygenic risk score (PRS) for schizophrenia in a sample of 623 psychiatrically healthy, non-clinical subjects from the FOR2107 multi-centre study and a second sample of 1133 blood donors.

Results: We did not find correlations of schizophrenia PRS with either overall SPQ or specific dimension scores, nor with adjusted schizotypy scores derived from the SPQ (addressing inter-scale variance).