Analysis of exonic deletions in a large population study provides novel insights into NRXN1 pathology.

The NRXN1 locus is a hotspot for non-recurrent copy number variants and exon-disrupting NRXN1 deletions have been associated with increased risk of neurodevelopmental disorders in case-control studies. However, corresponding population-based estimates of prevalence and disease-associated risk are currently lacking. Also, most studies have not differentiated between deletions affecting exons of different NRXN1 splice variants nor considered intronic deletions.

Evaluating the Joint Effects of Recurrent Copy Number Variants and Polygenic Scores on the Risk of Psychiatric Disorders in the iPSYCH2015 Case-Cohort Sample.

The impact of rare recurrent copy number variants (rCNVs) and polygenic background attributed to common variants, on the risk of psychiatric disorders is well-established in separate studies. However, it remains unclear how polygenic background modulates the effect of rCNVs. Using the population-representative iPSYCH2015 case-cohort sample (N=96,599), we investigated the association between absolute risk of psychiatric disorders and carriage of rCNVs and polygenic scores (PGS), as well as the interaction effect between the two on disease risk.

Population-Based Risk of Psychiatric Disorders Associated With Recurrent Copy Number Variants.

Importance: Recurrent copy number variants (rCNVs) have been associated with increased risk of psychiatric disorders in case-control studies, but their population-level impact is unknown.

Objective: To provide unbiased population-based estimates of prevalence and risk associated with psychiatric disorders for rCNVs and to compare risks across outcomes, rCNV dosage type (deletions or duplications), and locus features.

Design, Setting, And Participants: This genetic association study is an analysis of data from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) case-cohort sample of individuals born in Denmark in 1981-2008 and followed up until 2015, including (1) all individuals (n = 92 531) with a hospital discharge diagnosis of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder, major depressive disorder (MDD), or schizophrenia spectrum disorder (SSD) and (2) a subcohort (n = 50 625) randomly drawn from the source population.

Quantifying the relative importance of genetics and environment on the comorbidity between mental and cardiometabolic disorders using 17 million Scandinavians.

Mental disorders are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders. Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and near-complete genealogies of Denmark and Sweden (n = 17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six mental disorders and 15 cardiometabolic disorders.

Polygenic profiles define aspects of clinical heterogeneity in attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a complex disorder that manifests variability in long-term outcomes and clinical presentations. The genetic contributions to such heterogeneity are not well understood. Here we show several genetic links to clinical heterogeneity in ADHD in a case-only study of 14,084 diagnosed individuals.

Population-based Risk of Psychiatric Disorders Associated with Recurrent CNVs.

Recurrent copy number variants (rCNVs) are associated with increased risk of neuropsychiatric disorders but their pathogenic population-level impact is unknown. We provide population-based estimates of rCNV-associated risk of neuropsychiatric disorders for 34 rCNVs in the iPSYCH2015 case-cohort sample (n=120,247). Most observed significant increases in rCNV-associated risk for ADHD, autism or schizophrenia were moderate (HR:1.

Experience of loneliness during the COVID-19 pandemic: a cross-sectional study of 50 968 adult Danes.

Objectives: To examine the level of loneliness experienced during the COVID-19 pandemic in Denmark and to identify associated behavioural patterns and demographic factors.

Design: Cross-sectional cohort study.

Setting: Includes Danish active and former blood donors.

Associations of psychiatric disorders with sex chromosome aneuploidies in the Danish iPSYCH2015 dataset: a case-cohort study.

Background: Increased prevalence of mental illness has been reported in clinical studies of sex chromosome aneuploidies, but accurate population-based estimates of the prevalence and clinical detection rate of sex chromosome aneuploidies and the associated risks of psychiatric disorders are needed. In this study, we provide such estimates, valid for children and young adults of the contemporary Danish population.

Methods: We used the iPSYCH2015 case-cohort dataset, which is based on a source population of single-born individuals born in Denmark between May 1, 1981, and Dec 31, 2008.

Accurate and Effective Detection of Recurrent Copy Number Variants in Large SNP Genotype Datasets.

Structural variations, including recurrent Copy Number Variants (CNVs) at specific genomic loci, have been found to be associated with increased risk of several diseases and syndromes. CNV carrier status can be determined in large collections of samples using SNP arrays and, more recently, sequencing data. Although there is some consensus among researchers about the essential steps required in such analysis (i.

A comprehensive map of genetic relationships among diagnostic categories based on 48.6 million relative pairs from the Danish genealogy.

For more than half a century, Denmark has maintained population-wide demographic, health care, and socioeconomic registers that provide detailed information on the interaction between all residents and the extensive national social services system. We leverage this resource to reconstruct the genealogy of the entire nation based on all individuals legally residing in Denmark since 1968. We cross-reference 6,691,426 individuals with nationwide health care registers to estimate heritability and genetic correlations of 10 broad diagnostic categories involving all major organs and systems.

Comparing Copy Number Variations in a Danish Case Cohort of Individuals With Psychiatric Disorders.

Importance: Although the association between several recurrent genomic copy number variants (CNVs) and mental disorders has been studied for more than a decade, unbiased, population-based estimates of the prevalence, disease risks and trajectories, fertility, and mortality to contrast chromosomal abnormalities and advance precision health care are lacking.

Objective: To generate unbiased, population-based estimates of prevalence, disease risks and trajectories, fertility, and mortality of CNVs implicated in neuropsychiatric disorders.

Design, Setting, And Participants: In a population-based case-cohort study, using the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) 2012 database, individuals born between May 1, 1981, and December 31, 2005, and followed up until December 31, 2012, were analyzed.

Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.

Heritability of Schizophrenia and Schizophrenia Spectrum Based on the Nationwide Danish Twin Register.

Background: Twin studies have provided evidence that both genetic and environmental factors contribute to schizophrenia (SZ) risk. Heritability estimates of SZ in twin samples have varied methodologically. This study provides updated heritability estimates based on nationwide twin data and an improved statistical methodology.

Is an Early Age at Illness Onset in Schizophrenia Associated With Increased Genetic Susceptibility? Analysis of Data From the Nationwide Danish Twin Register.

Background: Early age at illness onset has been viewed as an important liability marker for schizophrenia, which may be associated with an increased genetic vulnerability. A twin approach can be valuable, because it allows for the investigation of specific illness markers in individuals with a shared genetic background.

Methods: We linked nationwide registers to identify a cohort of twin pairs born in Denmark from 1951 to 2000 (N=31,524 pairs), where one or both twins had a diagnosis in the schizophrenia spectrum.

A nation-wide study of the family aggregation and risk factors in anorexia nervosa over three generations.

Objective: This nation-wide register-based study investigated how often anorexia nervosa (AN) and co-morbid disorders occur in affected families compared with control families. Furthermore, the study addressed the impact of sex, year of birth, and degree of urbanization in terms of risk factors.

Method: A total of N = 2,370 child and adolescent psychiatric subjects born between 1951 and 1996 and registered in the Danish Psychiatric Central Research Register (DPCRR) had any mental disorder before the age of 18 and developed AN at some point during their life-time.

Predicting ADHD in school age when using the Strengths and Difficulties Questionnaire in preschool age: a longitudinal general population study, CCC2000.

Indicated prevention of ADHD may reduce impairment and need of treatment in youth. The Strengths and Difficulties Questionnaire (SDQ) is a brief questionnaire assessing child mental health, reported to be a valid screening instrument for concurrent ADHD. This study aimed to examine the validity of using the SDQ in preschool age to predict ADHD in school age in a longitudinal design.

Family load estimates and risk factors of anxiety disorders in a nationwide three generation study.

The present study investigated how often anxiety disorders with different ages of onset occurred in affected families compared to control families. Furthermore, the study addressed the impact of sex, region of residence, year and month of birth, and parental age at birth. The sample included N=1373 child and adolescent psychiatric participants born between 1952 and 2000 and registered in the Danish Psychiatric Central Register (DPCR) who developed an anxiety disorder before the age of 18.

Family aggregation and risk factors of obsessive-compulsive disorders in a nationwide three-generation study.

Background: This nationwide register-based study investigates how often obsessive-compulsive disorders (OCD) with different age at diagnosis occur in affected families compared to control families. Furthermore, the study addresses the impact of certain risk factors, that is, sex, degree of urbanization, year of birth, and maternal and paternal age at birth.

Methods: A total of N = 2,057 child and adolescent psychiatric subjects born between 1952 and 2000 and registered in the Danish Psychiatric Central Research Register developed OCD before the age of 18.

The association between medication for attention-deficit/hyperactivity disorder and cancer.

Objective: A study on chromosomal abnormalities has raised concerns that medication with methylphenidate (MPH) for attention-deficit/hyperactivity disorders (ADHD) might increase the risk of cancer. We performed a rigorous test of the association between cancer and MPH and other drugs used for ADHD, based on data from nationwide Danish registers.

Methods: Data were linked from five registers containing information on a total of 21,186 patients with ADHD, their drug prescription rates, and associated cancer diagnoses between 1994 and 2010.

A three generations nation-wide population study of family load estimates in bipolar disorder with different age at onset.

Objectives: This nation-wide register-based study investigates how often bipolar disorder (BD) occurs in affected families compared to control families by estimating the family load as a random effect; this effect measures the degree of dependence among family members in relation to BD. Furthermore, the study addresses the impact of certain risk factors, namely, sex, age at onset of BD, degree of urbanization, year of birth, month of birth, and maternal and paternal age at birth.

Method: A total of N=1204 children and adolescent psychiatric cases born between 1950 and 1997 and registered in the Danish Central Psychiatric Register (DPCR) developed BD before the age of 58 years.

Family load estimates of schizophrenia and associated risk factors in a nation-wide population study of former child and adolescent patients up to forty years of age.

Objectives: This nation-wide register-based study investigates the family load of schizophrenia (SZ) across three generations in affected families compared to control families. Furthermore the study compares the family load in case vs. control families considering the age of onset of the disorder in the cases.