Geographic variation of recorded neurodevelopmental disorders in children and adults.

Introduction: While diagnosis rates of autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) vary within countries at a large-scale municipal level, small neighbourhood geographic variation remains understudied. In this nationwide study, we describe the rates of ASD and ADHD diagnoses in children and adults by geographical data zones of approximately 2,500 residents across Denmark.

Methods: We included a population of children born from 1993 through 2020 and an adult population born from 1977 through 2003.

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.

The role of co-occurring conditions and genetics in the associations of eating disorders with attention-deficit/hyperactivity disorder and autism spectrum disorder.

Eating disorders (EDs) commonly co-occur with other psychiatric and neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD); however, the pattern of family history and genetic overlap among them requires clarification. This study investigated the diagnostic, familial, and genetic associations of EDs with ADHD and ASD. The nationwide population-based cohort study included all individuals born in Denmark, 1981-2008, linked to their siblings and cousins.

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.

3-generation family histories of mental, neurologic, cardiometabolic, birth defect, asthma, allergy, and autoimmune conditions associated with autism: An open-source catalog of findings.

The relatively few conditions and family member types (e.g., sibling, parent) considered in investigations of family health history in autism spectrum disorder (ASD, or autism) limits understanding of the role of family history in autism etiology.

White blood cell counts, ratios, and C-reactive protein among individuals with schizophrenia spectrum disorder and associations with long-term outcomes: a population-based study.

Background: Immune mechanisms are associated with adverse outcomes in schizophrenia; however, the predictive value of various peripheral immune biomarkers has not been collectively investigated in a large cohort before.

Objective: To investigate how white blood cell (WBC) counts, ratios, and C-Reactive Protein (CRP) levels influence the long-term outcomes of individuals with schizophrenia spectrum disorder (SSD).

Methods: We identified all adults in the Central Denmark Region during 1994-2013 with a measurement of WBC counts and/or CRP at first diagnosis of SSD.

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.

Shared familial risk for type 2 diabetes mellitus and psychiatric disorders: a nationwide multigenerational genetics study.

Background: Psychiatric disorders and type 2 diabetes mellitus (T2DM) are heritable, polygenic, and often comorbid conditions, yet knowledge about their potential shared familial risk is lacking. We used family designs and T2DM polygenic risk score (T2DM-PRS) to investigate the genetic associations between psychiatric disorders and T2DM.

Methods: We linked 659 906 individuals born in Denmark 1990-2000 to their parents, grandparents, and aunts/uncles using population-based registers.

Diagnosed eating disorders in Danish registers - incidence, prevalence, mortality, and polygenic risk.

Eating disorders are a group of severe and potentially enduring psychiatric disorders associated with increased mortality. Compared to other severe mental illnesses, they have received relatively limited research attention. Epidemiological studies often only report relative measures despite these being difficult to interpret having limited practical use.

A comprehensive analysis of age of onset and cumulative incidence of mental disorders: A Danish register study.

Background: The age of onset (AOO), incidence and cumulative incidence of mental disorders are critical epidemiological measures, providing essential insights into the development and course of these disorders across the lifespan. This study aims to provide up-to-date estimates of the AOO, age-specific incidence, and cumulative incidence for a comprehensive range of mental disorders using data from Danish registers.

Methods: We conducted a follow-up study encompassing all Danish residents from January 1, 2004, to December 31, 2021, totaling 91,613,465 person-years.

Interplay of polygenic liability with birth-related, somatic, and psychosocial factors in anorexia nervosa risk: a nationwide study.

Background: Although several types of risk factors for anorexia nervosa (AN) have been identified, including birth-related factors, somatic, and psychosocial risk factors, their interplay with genetic susceptibility remains unclear. Genetic and epidemiological interplay in AN risk were examined using data from Danish nationwide registers. AN polygenic risk score (PRS) and risk factor associations, confounding from AN PRS and/or parental psychiatric history on the association between the risk factors and AN risk, and interactions between AN PRS and each level of target risk factor on AN risk were estimated.

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.

3-generation family histories of mental, neurologic, cardiometabolic, birth defect, asthma, allergy, and autoimmune conditions associated with autism: an open-source catalogue of findings.

The relatively few conditions and family members investigated in autism family health history limits etiologic understanding. For more comprehensive understanding and hypothesis-generation we produced an open-source catalogue of autism associations with family histories of mental, neurologic, cardiometabolic, birth defect, asthma, allergy, and autoimmune conditions. All live births in Denmark, 1980-2012, of Denmark-born parents (1,697,231 births), and their 3-generation family members were followed through April 10, 2017 for each of 90 diagnoses (including autism), emigration or death.

Postpartum and non-postpartum depression: a population-based matched case-control study comparing polygenic risk scores for severe mental disorders.

It remains inconclusive whether postpartum depression (PPD) and depression with onset outside the postpartum period (MDD) are genetically distinct disorders. We aimed to investigate whether polygenic risk scores (PGSs) for major mental disorders differ between PPD cases and MDD cases in a nested case-control study of 50,057 women born from 1981 to 1997 in the iPSYCH2015 sample in Demark. We identified 333 women with first-onset postpartum depression (PPD group), who were matched with 993 women with first-onset depression diagnosed outside of postpartum (MDD group), and 999 female population controls.

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.