Publications by authors named "Markus M Nothen"

Objectives: C-Reactive Protein (CRP) values are partly determined by variation at the CRP gene locus, but also influenced by socioeconomic position (SEP) and related lifestyle factors. As gene-by-SEP interactions have been suggested for traits associated with CRP and SEP (e.g.

View Article and Find Full Text PDF

Courses of SARS-CoV-2 infections are highly variable, ranging from asymptomatic to lethal COVID-19. Though research has shown that host genetic factors contribute to this variability, cohort-based joint analyses of variants from the entire allelic spectrum in individuals with confirmed SARS-CoV-2 infections are still lacking. Here, we present the results of whole genome sequencing in 1,220 mainly vaccine-naïve individuals with confirmed SARS-CoV-2 infection, including 827 hospitalized COVID-19 cases.

View Article and Find Full Text PDF

Male-pattern hair loss (MPHL) is the most common form of hair loss in humans. Limited treatment options exist, which are not curative and vary in efficacy and invasiveness. Therapeutic and cosmetic hair growth stimulating agents that alleviate hair loss at a low risk of side effects are therefore of interest.

View Article and Find Full Text PDF

Procedural learning and automatization have widely been studied in behavioral psychology and typically involves a rapid improvement, followed by a plateau in performance throughout repeated training. More recently, brain imaging studies have implicated frontal-striatal brain circuits in skill learning. However, it is largely unknown whether frontal-striatal activation during skill learning and behavioral changes follow a similar learning curve pattern.

View Article and Find Full Text PDF

Disorders across the affective disorders-psychosis spectrum such as major depressive disorder (MDD), bipolar disorder (BD), schizoaffective disorder (SCA), and schizophrenia (SCZ), have overlapping symptomatology and high comorbidity rates with other mental disorders. So far, however, it is largely unclear why some of the patients develop comorbidities. In particular, the specific genetic architecture of comorbidity and its relationship with brain structure remain poorly understood.

View Article and Find Full Text PDF

Importance: Aortic stenosis (AS) and coronary artery disease (CAD) frequently coexist. However, it is unknown which genetic and cardiovascular risk factors might be AS-specific and which could be shared between AS and CAD.

Objective: To identify genetic risk loci and cardiovascular risk factors with AS-specific associations.

View Article and Find Full Text PDF
Article Synopsis
  • Subcortical brain structures play a crucial role in various developmental and psychiatric disorders, and a study analyzed brain volumes in 74,898 individuals, identifying 254 genetic loci linked to these volumes, which accounted for up to 35% of variation.
  • The research included exploring gene expression in specific neural cell types, focusing on genes involved in intracellular signaling and processes related to brain aging.
  • The findings suggest that certain genetic variants not only influence brain volume but also have potential causal links to conditions like Parkinson’s disease and ADHD, highlighting the genetic basis for risks associated with neuropsychiatric disorders.
View Article and Find Full Text PDF
Article Synopsis
  • Structural and functional changes in the brain are linked to cocaine use disorder (CUD), with epigenetic and transcriptional alterations serving as potential molecular causes for these changes.
  • A study analyzing brain tissue from individuals with CUD identified significant differences in gene expression, particularly highlighting an upregulation of the gene ZFAND2A and changes in alternative splicing that affect neuron pathways.
  • The findings suggest important biological processes like synaptic signaling and neuron morphogenesis are disrupted in CUD, and propose that drugs targeting glucocorticoid receptors could help reverse these expression changes.
View Article and Find Full Text PDF
Article Synopsis
  • Subcortical brain structures play a crucial role in various disorders, and a study analyzed the genetic basis of brain volumes in nearly 75,000 individuals of European ancestry, revealing 254 loci linked to these volumes.
  • The research identified significant gene expression in neural cells, relating to brain aging and signaling, and found that polygenic scores could predict brain volumes across different ancestries.
  • The study highlights genetic connections between brain volumes and conditions like Parkinson's disease and ADHD, suggesting specific gene expression patterns could be involved in neuropsychiatric disorders.
View Article and Find Full Text PDF

A previously published genome-wide association study (GWAS) meta-analysis across eight neuropsychiatric disorders identified antagonistic single-nucleotide polymorphisms (SNPs) at eleven genomic loci where the same allele was protective against one neuropsychiatric disorder and increased the risk for another. Until now, these antagonistic SNPs have not been further investigated regarding their link to brain structural phenotypes. Here, we explored their associations with cortical surface area and cortical thickness (in 34 brain regions and one global measure each) as well as the volumes of eight subcortical structures using summary statistics of large-scale GWAS of brain structural phenotypes.

View Article and Find Full Text PDF

Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly often accompanied by other structural anomalies and/or neurobehavioral manifestations. Rare de novo protein-coding variants and copy-number variations contribute to CDH in the population. However, most individuals with CDH remain genetically undiagnosed.

View Article and Find Full Text PDF

This review article provides insights into the role of genetic diagnostics in adult mental health disorders. The importance of genetic factors in the development of mental illnesses, from rare genetic syndromes to common complex genetic disorders, is described. Current clinical characteristics that may warrant a genetic diagnostic work-up are highlighted, including intellectual disability, autism spectrum disorders and severe psychiatric conditions with specific comorbidities, such as organ malformations or epilepsy.

View Article and Find Full Text PDF

Introduction: Formal genetics studies show that smoking is influenced by genetic factors; exploring this on the molecular level can offer deeper insight into the etiology of smoking behaviours.

Methods: Summary statistics from the latest wave of the GWAS and Sequencing Consortium of Alcohol and Nicotine (GSCAN) were used to calculate polygenic risk scores (PRS) in a sample of ~2200 individuals who smoke/individuals who never smoked. The associations of smoking status with PRS for Smoking Initiation (i.

View Article and Find Full Text PDF

Genome-wide association studies (GWASs) based on common single nucleotide polymorphisms (SNPs) have identified several loci associated with the risk of monoclonal gammopathy of unknown significance (MGUS), a precursor condition for multiple myeloma (MM). We hypothesized that analyzing haplotypes might be more useful than analyzing individual SNPs, as it could identify functional chromosomal units that collectively contribute to MGUS risk. To test this hypothesis, we used data from our previous GWAS on 992 MGUS cases and 2910 controls from three European populations.

View Article and Find Full Text PDF
Article Synopsis
  • * A genome-wide association meta-analysis of nearly 122,000 ANX cases revealed 58 significant genetic variants and 66 related genes, with many of these findings replicated in a larger independent sample.
  • * The findings indicate a substantial genetic overlap between ANX and other conditions like depression, emphasizing GABAergic signaling as a key mechanism, thereby enhancing our understanding of the genetic basis of ANX for future research.
View Article and Find Full Text PDF
Article Synopsis
  • Dysmorphologists face challenges due to the diverse phenotypic variability of human faces, particularly when using Next-Generation Phenotyping (NGP) tools, which are often trained on limited data.
  • To address this, the GestaltMatcher Database (GMDB) was created, compiling over 10,980 facial images from various global populations, significantly improving the representation of underrepresented ancestries, especially African and Asian patients.
  • The study found that incorporating data from non-European patients enhanced NGP accuracy by over 11% without compromising performance for European patients, highlighting the importance of diverse datasets in identifying genetic disorders.
View Article and Find Full Text PDF
Article Synopsis
  • - The study explores the connections between dimensional psychopathological syndromes and brain structure/function in patients with Major Depressive Disorder, Bipolar Disorder, Schizoaffective Disorder, and Schizophrenia, analyzing data from 1,038 individuals.
  • - Researchers identified three main psychopathological factors—paranoid-hallucinatory syndrome, mania, and depression—and found significant brain volume and cortical thickness differences linked to the paranoid-hallucinatory syndrome.
  • - Genome-wide association studies revealed significant genetic associations for mania and depression, suggesting a need for more dimensional perspectives in psychiatric classifications to improve understanding and treatment.
View Article and Find Full Text PDF

Short telomeres are associated with cardiovascular disease (CVD). We aimed to investigate, if genetically determined telomere-length effects CVD-risk in the Heinz-Nixdorf-Recall study (HNRS) population. We selected 14 single-nucleotide polymorphisms (SNPs) associated with telomere-length (p<10-8) from the literature and after exclusion 9 SNPs were included in the analyses.

View Article and Find Full Text PDF

Reduced processing speed is a core deficit in major depressive disorder (MDD) and has been linked to altered structural brain network connectivity. Ample evidence highlights the involvement of genetic-immunological processes in MDD and specific depressive symptoms. Here, we extended these findings by examining associations between polygenic scores for tumor necrosis factor-α blood levels (TNF-α PGS), structural brain connectivity, and processing speed in a large sample of MDD patients.

View Article and Find Full Text PDF

Aim: We investigated the predictive value of polygenic risk scores (PRS) derived from the schizophrenia GWAS (Trubetskoy et al., 2022) (SCZ3) for phenotypic traits of bipolar disorder type-I (BP-I) in 1878 BP-I cases and 2751 controls from Romania and UK.

Methods: We used PRSice-v2.

View Article and Find Full Text PDF
Article Synopsis
  • The study investigates the genetic factors contributing to coronary artery spasm (CAS) in European patients with angina and unobstructed coronary arteries, particularly focusing on variants from 208 cardiovascular-related genes.
  • Although no findings met the genome-wide significance threshold, suggestive genetic associations were found for focal and diffuse epicardial CAS, particularly relating to genes CDH13 and HDAC9, EDN1 respectively.
  • The research suggests that EDN1 may be a potential genetic risk factor for diffuse epicardial CAS, with elevated plasma endothelin-1 levels identified as a possible cardiac marker.
View Article and Find Full Text PDF

Purpose: BioMD-Y is a comprehensive biobank study of children and adolescents with major depression (MD) and their healthy peers in Germany, collecting a host of both biological and psychosocial information from the participants and their parents with the aim of exploring genetic and environmental risk and protective factors for MD in children and adolescents.

Participants: Children and adolescents aged 8-18 years are recruited to either the clinical case group (MD, diagnosis of MD disorder) or the typically developing control group (absence of any psychiatric condition).

Findings To Date: To date, four publications on both genetic and environmental risk and resilience factors (including , glucocorticoid receptor activation, polygenic risk scores, psychosocial and sociodemographic risk and resilience factors) have been published based on the BioMD-Y sample.

View Article and Find Full Text PDF

Background: Understanding the biological processes that underlie individual differences in emotion regulation and stress responsivity is a key challenge for translational neuroscience. The gene FKBP5 is a core regulator in molecular stress signaling that is implicated in the development of psychiatric disorders. However, it remains unclear how FKBP5 DNA methylation in peripheral blood is related to individual differences in measures of neural structure and function and their relevance to daily-life stress responsivity.

View Article and Find Full Text PDF