Publications by authors named "Caroline Nievergelt"

In recent years, significant efforts have been made to improve methods for genomic studies of admixed populations using local ancestry inference (LAI). Accurate LAI is crucial to ensure that downstream analyses accurately reflect the genetic ancestry of research participants. Here, we test analytic strategies for LAI to provide guidelines for optimal accuracy, focusing on admixed populations reflective of Latin America's primary continental ancestries-African (AFR), Amerindigenous (AMR), and European (EUR).

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  • The study explores the biological differences linked to PTSD by examining DNA methylation changes in blood, suggesting they could indicate susceptibility or effects of trauma.
  • Conducted by the Psychiatric Genomics Consortium, the research included nearly 5,100 participants to identify specific genetic markers associated with PTSD.
  • Results showed 11 significant CpG sites related to PTSD, with some also showing correlations between blood and brain tissue methylation, highlighting their potential role in understanding PTSD biology.
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Genetic contributions to human cortical structure manifest pervasive pleiotropy. This pleiotropy may be harnessed to identify unique genetically-informed parcellations of the cortex that are neurobiologically distinct from functional, cytoarchitectural, or other cortical parcellation schemes. We investigated genetic pleiotropy by applying genomic structural equation modeling (SEM) to map the genetic architecture of cortical surface area (SA) and cortical thickness (CT) for 34 brain regions recently reported in the ENIGMA cortical GWAS.

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  • Researchers aimed to create and validate Methylation Risk Scores (MRS) using machine learning to identify individuals at risk for PTSD based on genomic and trauma exposure data.
  • The study developed three models: eMRS (which combines trauma exposure and methylation data), MoRS (which relies only on methylation data), and MoRSAE (which adjusts MoRS for trauma exposure).
  • The eMRS model showed the best performance with a 92% accuracy, and all models were able to predict post-deployment PTSD significantly, suggesting that including trauma exposure improves risk assessment.
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In recent years, significant efforts have been made to improve methods for genomic studies of admixed populations using Local Ancestry Inference (LAI). Accurate LAI is crucial to ensure downstream analyses reflect the genetic ancestry of research participants accurately. Here, we test analytic strategies for LAI to provide guidelines for optimal accuracy, focusing on admixed populations reflective of Latin America's primary continental ancestries - African (AFR), Amerindigenous (AMR), and European (EUR).

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  • The study investigates the link between post-traumatic stress disorder (PTSD) and differences in DNA methylation, a type of gene regulation, in blood samples from individuals diagnosed with PTSD compared to trauma-exposed controls.
  • Researchers conducted a large-scale analysis involving over 5,000 participants from various civilian and military studies, using standardized procedures for PTSD assessment and DNA methylation testing.
  • The results revealed 11 specific DNA methylation sites associated with PTSD, and found similarities in methylation patterns between blood and brain tissues, suggesting a biological basis for the condition.
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Background: Previous epidemiological research has linked posttraumatic stress disorder (PTSD) with specific physical health problems, but the comprehensive landscape of medical conditions associated with PTSD remains uncharacterized. Electronic health records provide an opportunity to overcome clinical knowledge gaps and uncover associations with biological relevance that potentially vary by sex.

Methods: PTSD was defined among biobank participants ( = 145,959) in 3 major healthcare systems using 2 ICD code-based definitions: broad (≥1 PTSD or acute stress codes vs.

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  • * A study of Marines showed that those with more unpredictable childhood experiences reported higher levels of depression both shortly after deployment and ten years later.
  • * The negative effects of childhood unpredictability on mood were linked to lower social support and higher perceived stress, indicating that enhancing childhood stability and social support could mitigate future mental health issues.
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The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) included the central nucleus of the amygdala, hippocampal dentate gyrus, and medial prefrontal cortex (mPFC). Genes and exons within the mPFC carried most disease signals replicated across two independent cohorts.

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  • Bipolar disorder (BD) features disrupted sleep patterns and nerve cell loss, with lithium being a common but variably effective treatment.
  • Research focused on how certain circadian genes and their interactions influence cell survival and lithium response using neurons from BD patients and regular controls.
  • Findings indicated that certain gene knockdowns affected cell survival differently between lithium responders and non-responders, suggesting complex roles of circadian rhythms in BD and lithium treatment efficacy.
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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.
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Observational studies suggest that posttraumatic stress disorder (PTSD) increases risk for various autoimmune diseases. Insights into shared biology and causal relationships between these diseases may inform intervention approaches to PTSD and co-morbid autoimmune conditions. We investigated the shared genetic contributions and causal relationships between PTSD, 18 autoimmune diseases, and 3 immune/inflammatory biomarkers.

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Importance: Migraine is a prevalent and debilitating condition that substantially impacts quality of life. Investigating migraine prevalence, associated comorbidities, and potential military service exposures in veterans, focusing on gender differences, is crucial for targeted interventions and management strategies.

Objective: To determine the prevalence of migraine, associated health comorbidities, and potential military service and environmental exposures among men and women US veterans using a large-scale epidemiological sample from the Million Veteran Program (MVP).

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Background: Incorporating genomic data into risk prediction has become an increasingly useful approach for rapid identification of individuals most at risk for complex disorders such as PTSD. Our goal was to develop and validate Methylation Risk Scores (MRS) using machine learning to distinguish individuals who have PTSD from those who do not.

Methods: Elastic Net was used to develop three risk score models using a discovery dataset (n = 1226; 314 cases, 912 controls) comprised of 5 diverse cohorts with available blood-derived DNA methylation (DNAm) measured on the Illumina Epic BeadChip.

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Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 17 likely causal SNPs for BD.

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  • Lithium is the primary treatment for bipolar disorder (BD), but how it works and predicts outcomes is not fully understood.
  • A previous study identified key cellular pathways linked to lithium response, including focal adhesion and PI3K-Akt signaling.
  • In this new study, researchers confirmed these pathways in a larger group of 2039 patients but found no connection with the extracellular matrix, suggesting that issues with neuronal growth signaling may impact lithium effectiveness.
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Tinnitus is a heritable, highly prevalent auditory disorder treated by multiple medical specialties. Previous GWAS indicated high genetic correlations between tinnitus and hearing loss, with little indication of differentiating signals. We present a GWAS meta-analysis, triple previous sample sizes, and expand to non-European ancestries.

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Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium.

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Genetic contributions to human cortical structure manifest pervasive pleiotropy. This pleiotropy may be harnessed to identify unique genetically-informed parcellations of the cortex that are neurobiologically distinct from functional, cytoarchitectural, or other cortical parcellation schemes. We investigated genetic pleiotropy by applying genomic structural equation modeling (SEM) to map the genetic architecture of cortical surface area (SA) and cortical thickness (CT) for the 34 brain regions recently reported in the ENIGMA cortical GWAS.

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Large-scale genetic studies of traumatic brain injury (TBI) are lacking; thus, our understanding of the influence of genetic factors on TBI risk and recovery is incomplete. This study aimed to conduct a genome-wide association study (GWAS) of TBI in VA Million Veteran Program (MVP) enrollees. Participants included a multi-ancestry cohort (European, African, and Hispanic ancestries; N = 304,485; 111,494 TBI cases, 192,991 controls).

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Introduction: Evidence suggests that executive function (EF) may play a key role in development of PTSD, possibly influenced by factors such as trauma type and timing. Since EF can be improved through intervention, it may be an important target for promoting resilience to trauma exposure. However, more research is needed to understand the relation between trauma exposure, EF, and PTSD.

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