Biology subjects

Heilmann-Heimbach, S.

Publications and source records attributed to Heilmann-Heimbach, S..

7 recordsLinked to original sources

bioRxiv2026

Multimodal evidence for impaired glymphatic brain clearance as a mediator of "inflammaging" in schizophrenia - integrating insights from in vivo neuroimaging, omics, and post-mortem single nucleus-RNA-Seq data

Persistent cognitive impairment and reduced life expectancy in schizophrenia may arise from inflammation-driven accelerated aging ("inflammaging"), yet the underlying mechanisms remain unclear. Impaired glymphatic clearance, dependent on polarized aquaporin-4 (AQP4) localization at astrocytic endfeet, offers a plausible mechanistic link between inflammation and brain aging. Here, we integrate in vivo neuroimaging with post-mortem single-nucleus transcriptomics from distinct patient cohorts to demonstrate glymphatic dysfunction in schizophrenia and define its molecular basis. We identify reduced astrocytic expression of components of the dystrophin-associated protein complex (SNTA1, DAG1) required for AQP4 polarization. Both in vivo neuroimaging and post-mortem gene expression signatures of glymphatic dysfunction are restricted to an inflammatory subgroup characterized by peripheral immune activation and pro-inflammatory glial transcriptional profiles. Moreover, imaging signatures of glymphatic impairment are associated with schizophrenia polygenic risk scores enriched for immune - and oxidative stress - related aging pathways as well as cognitive dysfunction. At the cellular level, glymphatic dysfunction coincides with loss of homeostatic programs in microglia and astrocytes, increased inflammatory signaling, and endothelial signatures of blood-brain barrier disruption. Across modalities, glymphatic impairment is linked to accelerated aging, including increased brain and epigenetic age, and aging-related gene expression signatures.

neuroscience↗

bioRxiv2023

Reference genome sequence of the solitary bee Camptopoeum friesei Mocsary, 1894 (Hymenoptera, Andrenidae)

Bees are major pollinators of flowering plants and thus are important ecosystem service providers for natural habitats and crops. Evolution led to a wide range of adaptations in behaviors, morphology and ecological traits. Many plants rely on specialized bee species for pollination events, and so this interdependence can make them increasingly vulnerable to ongoing threats of habitat loss and pesticide exposure. Studying the genomes of bee species across different life histories and ecological specializations can help understand the evolution of these traits more generally, but also inform conservation efforts for Camptopoeum friesei specifically. Here, we present the reference genome of the solitary bee Camptopoeum friesei (Arthropoda; Insecta; Hymenoptera; Andrenidae). C. friesei is highly dependent on steppe habitats where it nests in saline soils. Further, it is highly specialized (oligolectic) on a few Asteraceae: Centaurea and Cirsium, in particular on Centaurea stoebe. As a consequence of its high specialization level, it is of its ecological niche with an extremely scattered and rare habitat, C. friesei is highly threatened in central Europe, albeit local aggregations can be rich in individuals. The high-quality genome assembly for the colourful bee Camptopoeum friesei was generated using long-read PacBio HiFi in combination with chromatin conformation capture (Hi-C) sequencing. The genome spans 367.7 megabases (Mb), N50 of 25.2 Mb. The majority of the assembly is scaffolded into 10 chromosomes and harbours [~]40% repeats. Species taxonomyEukaryota; Opisthokonta; Metazoa; Eumetazoa; Bilateria; Protostomia; Ecdysozoa; Panarthropoda; Arthropoda; Mandibulata; Pancrustacea; Hexapoda; Insecta; Dicondylia; Pterygota; Neoptera; Endopterygota; Hymenoptera; Apocrita; Aculeata; Apoidea; Anthophila; Andrenidae; Panurginae; Panurgini; Camptopoeum friesei Mocsary, 1894 (NCBI:txid2918745)

zoology↗

bioRxiv2023

High quality genome assembly and annotation (v1) of the eukaryotic terrestrial microalga Coccomyxa viridis SAG 216-4

Unicellular green algae of the genus Coccomyxa are recognized for their worldwide distribution and ecological versatility. Most species described to date live in close association with various host species, such as in lichen associations. However, little is known about the molecular mechanisms that drive such symbiotic lifestyles. We generated a high-quality genome assembly for the lichen photobiont Coccomyxa viridis SAG 216-4 (formerly C. mucigena). Using long-read PacBio HiFi and Oxford Nanopore Technologies in combination with chromatin conformation capture (Hi-C) sequencing, we assembled the genome into 21 scaffolds with a total length of 50.9 Mb, an N50 of 2.7 Mb and a BUSCO score of 98.6%. While 19 scaffolds represent full-length nuclear chromosomes, two additional scaffolds represent the mitochondrial and plastid genomes. Transcriptome-guided gene annotation resulted in the identification of 13,557 protein-coding genes, of which 68% have annotated PFAM domains and 962 are predicted to be secreted.

genomics↗

bioRxiv2020

"The Heidelberg Five" Personality Dimensions: Genome-wide Associations, Polygenic Risk for Neuroticism, and Psychopathology 20 Years after Assessment

The HeiDE study ( Heidelberger Langzeitstudie zu Risikofaktoren und Diagnose chronischer Erkrankungen) is a longitudinal population-based study that started in the 1990s and, at baseline, assessed an array of health-related personality questionnaires in 5 133 individuals. Five latent personality dimensions (The Heidelberg Five) were identified and interpreted as Emotional Lability (ELAB), Lack of Behavioral Control (LBCN), Type A Behavior (TYAB), Locus of Control over Disease (LOCC), and Psychoticism (PSYC). A subset of participants (n=3 268; after quality control) were genotyped on whole-genome arrays at follow-up. To further characterize The Heidelberg Five, we analyzed genomic underpinnings, their relations to the genetic basis of the Big Five trait Neuroticism, and longitudinal associations with lifetime psychiatric symptoms. SNP-based heritability was significant for ELAB (34%) and LBCN (29%). Five separate genome-wide association studies (GWAS) using factor scores on personality dimensions as phenotypes were conducted, only the phenotype PSYC yielded a genome-wide significant finding (p<5x10-8, top SNP rs138223660). Gene-based analyses identified significant findings for ELAB (Integrin Subunit Beta 5), TYAB (Coiled-coil Domain Containing 83), and PSYC (Nuclear Receptor Subfamily 1 Group H Member 4). Polygenic risk scores for Neuroticism, phenotypically related to ELAB, were associated with ELAB, but not with the remaining Heidelberg Five. Longitudinally, all personality dimensions were related to depressive symptoms at follow-up, with ELAB, LBCN, and PSYC also associated with lifetime anxiety symptoms. These results highlight the clinical importance of health-related personality traits, and identify LBCN as a heritable "executive function" personality trait.

genomics↗

bioRxiv2018

Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families as well as 438 subjects from an independent, sporadic BD case-control cohort were analysed. Polygenic risk scores (PRS) for BD, schizophrenia, and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had significantly higher PRS for all three psychiatric disorders than the independent controls, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and sporadic BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses, therefore, demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. The PRS explained only part of the observed phenotypic variance and rare variants might have also contributed to disease development.

genetics↗

bioRxiv2018

Variants of DNMT3A cause transcript-specific DNA methylation patterns and affect hematopoietic differentiation

The de novo DNA methyltransferase 3A (DNMT3A) plays pivotal roles in hematopoietic differentiation. In this study, we followed the hypothesis that alternative splicing of DNMT3A has characteristic epigenetic and functional sequels. Specific DNMT3A transcripts were either downregulated or overexpressed in human hematopoietic stem and progenitor cells and this resulted in complementary and transcript-specific DNA methylation and gene expression changes. Functional analysis indicated that particularly transcript 2 (coding for DNMT3A2) activates proliferation and induces loss of a primitive immunophenotype, whereas transcript 4 interferes with colony formation of the erythroid lineage. Notably, in acute myeloid leukemia (AML) expression of transcript 2 correlates with its in vitro DNA methylation and gene expression signatures and is associated with overall survival, indicating that DNMT3A variants impact also on malignancies. Our results demonstrate that specific DNMT3A variants have distinct epigenetic and functional impact. Particularly DNMT3A2 triggers hematopoietic differentiation and the corresponding signatures are reflected in AML.

cell biology↗

bioRxiv2018

Trans-ancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest GWAS to date of DSM - IV diagnosed AD. Genome - wide data on 14,904 individuals with AD and 37,944 controls from 28 case / control and family - based studies were meta - analyzed, stratified by genetic ancestry (European, N = 46,568; African; N = 6,280). Independent, genome - wide significant effects of different ADH1B variants were identified in European (rs1229984; p = 9.8E - 13) and African ancestries (rs2066702; p = 2.2E - 9). Significant genetic correlations were observed with schizophrenia, ADHD, depression, and use of cigarettes and cannabis. There was only modest genetic correlation with alcohol consumption and inconsistent associations with problem drinking. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and non - pathological drinking behaviors.

genetics↗