Publications by authors named "Werge T"
Background: Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims: We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
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.
View Article and Find Full Text PDFThe potential of ancient DNA analyses to provide independent sources of information about events in the historical record remains to be demonstrated. Here we apply palaeogenomic analysis to human remains excavated from a medieval well at the ruins of Sverresborg Castle in central Norway. In , the Old Norse of King Sverre Sigurdsson, one passage details a 1197-CE raid on the castle and mentions a dead man thrown into the well.
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- Large biobank samples allow researchers to combine detailed family histories and genetic data to investigate complex diseases.
- The study introduces a new method called Pearson-Aitken Family Genetic Risk Scores (PA-FGRS) to estimate disease risk based on family medical histories.
- Applying PA-FGRS to major depressive disorder (MDD) shows improved understanding of genetic factors and clinical variability, and enhances the effectiveness of genetic studies across different complex conditions.
Background: It is known that impairments in linguistic ability and motor function tend to co-occur in children, and that children from families with parental mental illness such as schizophrenia tend to perform poorly in both domains, but the exact nature of these links has not yet been fully elucidated.
Design: In this study, we leveraged the first wave of the Danish High Risk and Resilience Study (VIA 7), which includes both genetic data and measures covering multiple developmental domains. The VIA 7 cohort comprises 522 7-year-old children born to parents with schizophrenia (N = 202), bipolar disorder (N = 120) or neither (N = 200).
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.
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- The study explores how genetic factors (polygenic scores or PGS) for psychiatric disorders affect the treatment trajectories of individuals with early-onset Major Depressive Disorder (MDD) in secondary care.
- Researchers used data from a large Danish sample, analyzing 10,577 individuals diagnosed with MDD between ages 10-25 to identify different patterns of treatment over seven years.
- Findings reveal specific associations between PGS for ADHD and anorexia with treatment trajectories, suggesting that while genetics may influence the path of depression treatment, the effects are small and not currently useful for predicting clinical outcomes.
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- Tic disorders (TD) can significantly affect individuals and society, and understanding their genetic causes could lead to better treatments, as family history is a key risk factor.
- A large-scale GWAS meta-analysis was conducted with nearly 10,000 TD cases and over 981,000 controls, revealing a significant genetic association, though it couldn't be replicated in another study.
- The findings suggest a complex genetic landscape for TD, highlighting certain genes and brain regions involved, but additional research is needed to firmly establish reliable genetic links.
Emerging evidence has shown that assortative mating (AM) is a key factor that shapes the landscape of complex human traits. It can increase the overall prevalence of disorders, influence occurrences of comorbidities, and bias estimation of genetic architectures. However, there is lack of large-scale studies to examine the cultural differences and the generational trends of AM for psychiatric disorders.
View Article and Find Full Text PDFDevelopmental language disorder (DLD) is a neurodevelopmental disorder primarily affecting language in the absence of a known biomedical condition, which may have a large impact on a person's life and mental health. Family-based studies indicate a strong genetic component in DLD, but genetic studies of DLD are scarce. In this study we estimated the heritability of DLD and its genetic correlations with related disorders and traits in sample of >25,000 individuals from the Danish Blood Donor Study for whom we had both genotype data and questionnaire data on language disorder and language support.
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- - ADHD is a neurodevelopmental disorder often identified in childhood, with both genetic and environmental risk factors influencing its development, including maternal infections during pregnancy.
- - A study measuring immune responses to various microorganisms in newborns found a significant association between higher antibody levels against cytomegalovirus (CMV) and mycoplasma with later ADHD diagnosis.
- - There is a suggested dose-response relationship indicating that increased immune system activation before or at birth may elevate the risk of ADHD, highlighting the need for healthy pregnancy practices to minimize infection risks.
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- - MDD and CVD commonly occur together, leading to higher health risks, and they share many genetic risk factors, with notable genetic overlaps found in specific brain regions like the thalamus.
- - The research identified seven genetic loci linked to both disorders and highlighted that factors like inflammation and lifestyle contribute to the shared risk between MDD and atherosclerotic CVD.
- - The findings suggest that genetic predisposition to MDD increases the risk of CVD, while the reverse is less evident, indicating a specific immunometabolic subtype of MDD that may be targeted for better prevention of CVD.
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- - The study investigates childhood daytime urinary incontinence (DUI) by identifying genetic variants that increase the risk, shedding light on the condition which is often stigmatized and not well understood.
- - A genome-wide association study was performed on a large cohort from Denmark and replicated in Iceland, discovering significant genetic variants on chromosomes 6 and 20 linked to genes involved in neuronal development and bladder function.
- - The research found that DUI has a hereditary component and is genetically correlated with conditions like attention-deficit/hyperactivity disorder and BMI, suggesting new directions for treatment options.
The 22q11.2 deletion syndrome (22q11.2DS) is associated with high psychiatric morbidity.
View Article and Find Full Text PDFImportance: 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.
Article Synopsis
- Major depressive disorder (MDD) and cardiovascular disease (CVD) often occur together, leading to increased health issues and mortality rates.
- A study discovered that many genetic risk factors for CVD overlap with those for MDD, indicating a shared biological basis, particularly involving specific brain regions and cell types.
- The findings suggest that genetic predisposition to MDD can increase the risk of developing CVD, while lifestyle and metabolic factors also play significant roles, potentially creating an immunometabolic subtype of MDD more closely linked with CVD.
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.
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- Obsessive-compulsive disorder (OCD) affects about 1% of people and has a strong genetic component, but previous studies have not fully explained its genetic causes or biological mechanisms.
- A large genome-wide association study (GWAS) analyzed data from over 53,000 OCD cases and over 2 million control participants, identifying 30 significant genetic markers related to OCD and suggesting a 6.7% heritability from SNPs.
- The research also found 249 candidate risk genes linked to OCD, particularly in specific brain regions, and showed genetic correlations with various psychiatric disorders, laying the groundwork for further studies and potential treatments.
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- PTSD genetics have been difficult to study compared to other psychiatric disorders, limiting our biological understanding of the condition.
- A large-scale meta-analysis involving over 1.2 million individuals identified 95 genome-wide significant loci, with 80 being new discoveries related to PTSD.
- Researchers identified 43 potential causal genes linked to neurotransmitter activity, developmental processes, synaptic function, and immune regulation, enhancing our knowledge of the neurobiological systems involved in PTSD.
Article Synopsis
- Four GWAS studies on obsessive-compulsive disorder (OCD) have been conducted, showing a SNP-heritability of 28% but revealing only one significant SNP so far.
- A new meta-analysis significantly increased the sample size to analyze 37,015 OCD cases against 948,616 controls, identifying 15 independent genome-wide significant loci, 14 of which were novel.
- The research highlighted genetic correlations between OCD and various psychiatric disorders, while also mapping the genetic basis and biological pathways associated with OCD susceptibility.
Mental disorders (MDs) are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders (CMDs). Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and complete genealogies of Denmark and Sweden (n=17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six MDs and 14 CMDs.
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- Accurately diagnosing bipolar disorder (BD) can take around 7 years due to its overlap with unipolar major depressive disorder (MDD), especially since the first manic episode often follows a depressive one.
- This study uses genome-wide association analyses (GWAS) and polygenic risk scores (PRS) from a large cohort to identify genetic factors that could help differentiate between BD and MDD early on.
- The results show that while BD and MDD are genetically distinct and share a continuum of genetic risk, larger future studies are needed to enhance the accuracy of these genetic predictors for early diagnosis.