Genome-wide study of somatic symptom and related disorders identifies novel genomic loci and map genetic architecture.

Somatic symptom and related disorders (SSRD) are characterized by a mixture of neurological and psychiatric features and include functional neurological (FND) and somatic symptom disorders (SomD). While these complex neuropsychiatric disorders show evidence of genetic susceptibility, there are no genome-wide association studies (GWAS) of SSRD, and the heritability is unknown. We did a GWAS of a total of 22,203 patients with SSRD, and 1,831,107 controls of European ancestry.

Youth psychotic experiences: psychometric evaluation and diagnostic associations of the CAPE-16 in adolescents from the Norwegian Mother, Mather and Child Cohort.

Background: Adolescent self-reported psychotic experiences are associated with mental illness and could help guide prevention strategies. Youth report substantially more experiences than adults. However, with large societal changes like the digital revolution and COVID-19 pandemic, existing questionnaires may no longer accurately capture youth experiences.

Dissecting the Genetic Relationship Between Severe Mental Disorders and Autoimmune Diseases.

Severe mental disorders have been linked to immune system dysfunction. While a genetic association between mental disorders and autoimmune diseases has been suggested, their genetic relationship remains incompletely understood. Utilizing a complementary set of statistical analyses, we conducted a comprehensive investigation of the genetic architecture between severe mental disorders (major depression (MD), bipolar disorder (BD), and schizophrenia (SCZ)) and seven autoimmune diseases (autoimmune thyroiditis, celiac disease, inflammatory bowel disease (IBD), multiple sclerosis, psoriasis, rheumatoid arthritis, and type 1 diabetes), involving a total of 667,518 cases from 10 genome-wide association studies.

Multimodal Prediction of Psychosis in the Prospective MoBa Birth Cohort.

There is a need for improved early psychosis detection beyond the traditional clinical high-risk strategy. Using the Norwegian Mother, Father and Child cohort study, we examined the predictive ability of self-reported psychotic experiences (Community Assessment of Psychic Experiences; CAPE) at age 14, in addition to general mental health factors, parent and childhood psychiatric diagnoses, schizophrenia polygenic risk scores, and birth-related factors, to predict subsequent psychosis onset using three machine learning approaches for imbalanced data. We explored also a multimodal prediction framework.

Genetic overlap of severe psychiatric disorders with lung function and asthma suggests shared biological mechanisms.

Background: Severe psychiatric disorders are frequently comorbid with lung function decline and asthma. Despite their considerable heritability, the genetic relationships between them are unclear.

Methods: We investigated the shared genetic architecture for three severe psychiatric disorders (schizophrenia, bipolar disorder, and anorexia nervosa) with lung function and asthma using results from genome-wide association studies.

Nonlinearity and sex differences in the performance of a polygenic risk score for juvenile idiopathic arthritis.

Background: Juvenile idiopathic arthritis (JIA) is an immune-mediated pediatric disease believed to result from a complex interplay of genetic and environmental factors. Genome-wide association studies have enabled calculation of polygenic risk scores (PRS) for JIA. Understanding how the PRS associates with JIA and whether it performs similarly across sexes is essential for its utility in future studies.

FEMA-Long: Modeling unstructured covariances for discovery of time-dependent effects in large-scale longitudinal datasets.

Linear mixed-effects (LME) models are commonly used for analyzing longitudinal data. However, most applications of LME models rely on random intercepts or simple, e.g.

Mapping the genetic landscape of immune-mediated disorders: potential implications for classification and therapeutic strategies.

Objectives: Based on clinical, biomarker, and genetic data, McGonagle and McDermott suggested that autoimmune and autoinflammatory disorders can be classified as a disease continuum from purely autoimmune to autoinflammatory with mixed diseases in between. However, the genetic architecture of this spectrum has not been systematically described. Here, we investigate the continuum of polygenic immune-mediated disorders using genome-wide association studies (GWAS) and statistical genetics methods.

Brain-based gene expression and corresponding behavioural relevance of risk genes for broad antisocial behaviour.

Antisocial behaviour (ASB) involves persistent irresponsible, delinquent activities violating rights and safety of others. A meta-analysis of genome-wide association studies revealed significant genetic associations with ASB, yet their brain expression patterns and behavioural relevance remain unclear. Our investigation of fifteen genes associated with ASB examined their biological role and distribution across tissues, integrating post-mortem brain sample data from the Allen-Human-Brain Atlas and the Genotype-Tissue Expression project.

Polygenic overlap of substance use behaviors and disorders with externalizing and internalizing problems independent of genetic correlations.

Background: Externalizing and internalizing pathways may lead to the development of substance use behaviors (SUBs) and substance use disorders (SUDs), which are all heritable phenotypes. Genetic correlation studies have indicated differences in the genetic susceptibility between SUBs and SUDs. We investigated whether these substance use phenotypes are differently related to externalizing and internalizing problems at a genetic level.

Association of Polygenic Risk for Psychiatric Disorders with Cardiometabolic Disease.

Importance: Clinical diagnoses of psychiatric disorders are associated with cardiometabolic diseases (CMDs) such as type 2 diabetes and ischemic heart diseases. Studying how genetic liability for psychiatric disorders relate to CMD risk will offer novel insight into the relationship between psychiatric disorders and CMDs.

Objective: To evaluate the associations between psychiatric polygenic risk scores (PRSs) and clinically diagnosed CMDs while accounting for cross-disorder pleiotropy.

Maternal seafood intake, dietary contaminant exposure, and risk of juvenile idiopathic arthritis: exploring gene-environment interactions.

Objectives: Juvenile idiopathic arthritis (JIA) originates from a complex interplay between genetic and environmental factors. We investigated the association between seafood intake and dietary contaminant exposure during pregnancy and JIA risk, to identify sex differences and gene-environment interactions.

Methods: We used the Norwegian Mother, Father, and Child Cohort Study (MoBa), a population-based prospective pregnancy cohort (1999-2008).

Charting the shared genetic architecture of Alzheimer's disease, cognition, and educational attainment, and associations with brain development.

The observation that the risk of developing Alzheimer's disease is reduced in individuals with high premorbid cognitive functioning, higher educational attainment, and occupational status has led to the 'cognitive reserve' hypothesis. This hypothesis suggests that individuals with greater cognitive reserve can tolerate a more significant burden of neuropathological changes before the onset of cognitive decline. The underpinnings of cognitive reserve remain poorly understood, although a shared genetic basis between measures of cognitive reserve and Alzheimer's disease has been suggested.

Incidence and Genetic Risk of Juvenile Idiopathic Arthritis in Norway by Latitude.

Objective: We aimed to investigate the incidence of juvenile idiopathic arthritis (JIA) in the three geographic regions of Norway and whether potential regional incidence differences are explained by environmental or genetic factors across regions.

Methods: We conducted a register-based cohort study including all Norwegian children born from 2004 to 2019, with follow-up throughout 2020. The JIA diagnosis, defined by at least two International Classification of Diseases, Tenth Revision codes for JIA, was validated against medical records.

Leveraging the Genetics of Psychiatric Disorders to Prioritize Potential Drug Targets and Compounds.

Background: Genetics has the potential to inform biologically relevant drug treatment and repurposing which may ultimately improve patient care. In this study, we combine methods which leverage the genetics of psychiatric disorders to prioritize potential drug targets and compounds.

Methods: We used the largest available genome-wide association studies, in European ancestry, of four psychiatric disorders [i.

Youth Psychotic Experiences: Diagnostic Associations and Evaluation of the CAPE-16.

Background: Adolescent self-reported psychotic experiences are associated with mental illness and could help guide prevention strategies. The Community Assessment of Psychic Experiences (CAPE) was developed over 20 years ago. In a rapidly changing society, where new generations of adolescents are growing up in an increasingly digital world, it is crucial to ensure high reliability and validity of the questionnaire.

Dissecting the genetic overlap between three complex phenotypes with trivariate MiXeR.

Comorbidities are an increasing global health challenge. Accumulating evidence suggests overlapping genetic architectures underlying comorbid complex human traits and disorders. The bivariate causal mixture model (MiXeR) can quantify the polygenic overlap between complex phenotypes beyond global genetic correlation.

Polygenic liability for antipsychotic dosage and polypharmacy - a real-world registry and biobank study.

Genomic prediction of antipsychotic dose and polypharmacy has been difficult, mainly due to limited access to large cohorts with genetic and drug prescription data. In this proof of principle study, we investigated if genetic liability for schizophrenia is associated with high dose requirements of antipsychotics and antipsychotic polypharmacy, using real-world registry and biobank data from five independent Nordic cohorts of a total of N = 21,572 individuals with psychotic disorders (schizophrenia, bipolar disorder, and other psychosis). Within regression models, a polygenic risk score (PRS) for schizophrenia was studied in relation to standardized antipsychotic dose as well as antipsychotic polypharmacy, defined based on longitudinal prescription registry data as well as health records and self-reported data.

Conduct disorder - a comprehensive exploration of comorbidity patterns, genetic and environmental risk factors.

Conduct disorder (CD), a common mental disorder in children and adolescents, is characterized by antisocial behavior. Despite similarities with antisocial personality disorder (ASPD) and possible diagnostic continuity, CD has been shown to precede a range of adult-onset mental disorders. Additionally, little is known about the putative shared genetic liability between CD and adult-onset mental disorders and the underlying gene-environment interplay.