- E-postStephanie.LeHellard@uib.no
- Telefon+47 900 58 089
- BesøksadresseHaukeland universitetssykehus, Laboratoriebygget5009 BergenRom5310
- PostadressePostboks 78045020 Bergen
I am a Professor in Human Genetics at the department of Clinical Sciences, Facutly of Medicine. I am also a core researcher at the Norwegian Centre for Mental Disorders Research (NORMENT centre of excellence https://www.med.uio.no/norment/english/) and the Bergen Centre for Brain Plasticity (https://helse-bergen.no/en/bergen-center-for-brain-plasticity)
Together with the members of my group we are focusing our research on the Epigenetics of Mental Disorders and their treatment (incl. treatment response).
Most of mental disorders are multifactorial in nature, which means that several genetic risk factors combined with environmental risk factors increase the risk to develop a disorder.
Epigenetic modifications, are changes added to the DNA (without changing the DNA sequence) that can regulate the expression of genes, for example the addition of methylation groups on the DNA (aka DNA methylation). Some of these modifications can be dependent of the genetic background, on the biological development (age or sex) or influenced by the environment (e.g. risk factors or treatment). We are especially interested in DNA methylation differences between patients with mental disorders such as schizophrenia, bipolar disorder, anxiety, OCD... and controls. DNA methylation differences are also observed under exposure to some environmental factors such as smoking, stress, cannabis use, etc... There are also some studies that have reported how treatment with either antidepressant or with cognitive therapy can be associated with differences in DNA methylation.
Thus the aim of our research is to identify epigenetic factors associated with the different aspects of psychiatric disorders: the risk to develop such disorders and how to treat them.
Specifically our projects are aimed at:
- Investigating epigenetic modifications in schizophrenia, bipolar disorder and anxiety disorders.
- Molecular mechanisms of exposure to several environmental risk in patients with psychosis (cannabis, trauma, asphyxia, ...).
- Identification of regions of differential methylation across psychiatric disorders and through the life span.
- DNA methylation changes associated with treatment and treatment response in OCD, psychosis and depression.
The group currently consist of 1 senior researcher, 2 postdocs, 3 PhD students, 1 forskerlinje student, 1 bio-engineer and myself.
I am also project leader for the BRY.DEG2020 study which we intiated under the Covid19 outbreak in order to follow up what would be the effect of the epidemic and the restrictions taken, on the mental health of young adults (see www.uib.no/brydeg2020)
I teach Genetics and Evolution to medical students in their 3rd semester, at the Faculty of Medicine, UiB.
I teach a MSc course in Human Genetics (HUMGEN301) at the Faculty of Medicine, UiB.
I also participate in the IGSIN course for PhD students, UiB, and the Master course in Genetics of Cognitive Neuroscience at the University of Oslo.
Vitenskapelig artikkel
- (2024). Sex effects on DNA methylation affect discovery in epigenome-wide association study of schizophrenia. Molecular Psychiatry.
- (2024). Divergent epigenetic responses to perinatal asphyxia in severe mental disorders. Translational Psychiatry. 12 sider.
- (2023). Neurobiological mechanisms of ECT and TMS treatment in depression: study protocol of a multimodal magnetic resonance investigation. BMC Psychiatry.
- (2023). Differences in white blood cell proportions between schizophrenia cases and controls are influenced by medication and variations in time of day. Translational Psychiatry.
- (2023). Changes in mental health symptoms from April (COVID-19 outbreak) to December 2020 in Norway: A two-wave study. Cogent Psychology. 1-12.
- (2023). Beyond the Global Brain Differences: Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers. Biological Psychiatry. 147-160.
- (2022). Personality traits and hardiness as risk- and protective factors for mental distress during the COVID-19 pandemic: a Norwegian two-wave study. BMC Psychiatry. 1-10.
- (2022). Genetic variants associated with longitudinal changes in brain structure across the lifespan. Nature Neuroscience. 421-432.
- (2022). Changes in contamination-related obsessions and compulsions during the COVID-19 pandemic: A Norwegian longitudinal study. Journal of Obsessive-Compulsive and Related Disorders. 1-10.
- (2022). An epigenetic association analysis of childhood trauma in psychosis reveals possible overlap with methylation changes associated with PTSD. Translational Psychiatry.
- (2021). Mental health symptoms during the first months of the COVID-19 outbreak in Norway: A cross-sectional survey study. Scandinavian Journal of Public Health. 1-8.
- (2021). Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics. Neuropsychopharmacology. 1788-1801.
- (2021). Identification of pleiotropy at the gene level between psychiatric disorders and related traits. Translational Psychiatry. 8 sider.
- (2021). Cohort Profile: COVIDMENT: COVID-19 cohorts on mental health across six nations. International Journal of Epidemiology. 1-15.
- (2021). 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans. Translational Psychiatry. 16 sider.
- (2020). The genetic architecture of the human cerebral cortex. Science.
- (2020). The genetic architecture of human brainstem structures and their involvement in common brain disorders. Nature Communications. 14 sider.
- (2020). Shared genetic risk between eating disorder‐ and substance‐use‐related phenotypes: Evidence from genome‐wide association studies. Addiction Biology. 21 sider.
- (2020). Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease. Nature Genetics. 482-493.
- (2020). Genetic control of variability in subcortical and intracranial volumes. Molecular Psychiatry. 1-8.
- (2020). Cannabis Use Is Associated With Increased Levels of Soluble gp130 in Schizophrenia but Not in Bipolar Disorder. Frontiers in Psychiatry. 1-10.
- (2019). Pleiotropic meta-analysis of cognition, education, and schizophrenia differentiates roles of early neurodevelopmental and adult synaptic pathways. American Journal of Human Genetics. 334-350.
- (2019). Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders. Cell. 1469-1482.
- (2019). Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. Nature Genetics. 1207-1214.
- (2019). Genetic architecture of subcortical brain structures in 38,851 individuals. Nature Genetics. 1624-1636.
- (2019). Common brain disorders are associated with heritable patterns of apparent aging of the brain. Nature Neuroscience. 1617-1623.
- (2019). Association of copy number variation of the 15q11.2 BP1-BP2 region with cortical and subcortical morphology and cognition. JAMA psychiatry. 11 sider.
- (2018). Williams Syndrome neuroanatomical score associates with GTF2IRD1 in large-scale magnetic resonance imaging cohorts: A proof of concept for multivariate endophenotypes. Translational Psychiatry. 1-8.
- (2018). Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. Nature Communications. 1-16.
- (2018). Recently evolved human-specific methylated regions are enriched in schizophrenia signals. BMC Evolutionary Biology. 1-11.
- (2018). Meta-analysis of Alzheimer’s disease on 9,751 samples from Norway and IGAP study identifies four risk loci. Scientific Reports. 8 sider.
- (2018). Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence. Nature Genetics. 912-919.
- (2018). Genetic variation in 117 myelination-related genes in schizophrenia: Replication of association to lipid biosynthesis genes. Scientific Reports. 1-8.
- (2018). Genetic and transcriptional analysis of inflammatory bowel disease-associated pathways in patients with GUCY2C-linked familial diarrhea. Scandinavian Journal of Gastroenterology. 1264-1273.
- (2018). Elevated expression of a minor isoform of ANK3 is a risk factor for bipolar disorder. Translational Psychiatry. 1-10.
- (2018). Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes. Molecular Psychiatry. 1-13.
- (2018). Analysis of differentially methylated regions in great apes and extinct hominids provides support for the evolutionary hypothesis of schizophrenia. Schizophrenia Research. 8 sider.
- (2017). Sequencing and de novo assembly of 150 genomes from Denmark as a population reference. Nature. 87-91.
- (2017). Psychotic patients who used cannabis frequently before illness onset have higher genetic predisposition to schizophrenia than those who did not. Psychological Medicine. 43-49.
- (2017). Novel genetic loci associated with hippocampal volume. Nature Communications. 1-12.
- (2017). Large-scale cognitive GWAS meta-analysis reveals tissue-specific neural expression and potential nootropic drug targets. Cell reports. 2597-2613.
- (2017). Identification of gene loci that overlap between schizophrenia and educational attainment. Schizophrenia Bulletin. 654-664.
- (2017). GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report form the COGENT consortium. Molecular Psychiatry. 336-345.
- (2017). Assembly and analysis of 100 full MHC haplotypes from the Danish population. Genome Research. 1597-1607.
- (2017). Analysis of the joint effect of SNPs to identify independent loci and allelic heterogeneity in schizophrenia GWAS data. Translational Psychiatry.
- (2017). A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling. Scientific Reports. 1-9.
- (2017). A genetic association study of CSMD1 and CSMD2 with cognitive function. Brain, Behavior, and Immunity. 209-216.
- (2016). Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nature Neuroscience. 1569-1582.
- (2016). Nationwide genomic study in Denmark reveals remarkable population homogeneity. Genetics. 711-722.
- (2016). Genome-wide autozygosity is associated with lower general cognitive ability. Molecular Psychiatry. 837-843.
- (2016). Genetics of structural connectivity and information processing in the brain. Brain Structure and Function. 4643-4661.
- (2016). Genetic evidence for a role of the SREBP transcription system and lipid biosynthesis in schizophrenia and antipsychotic treatment. European Neuropsychopharmacology. 589-598.
- (2016). Conservation of Distinct Genetically-Mediated Human Cortical Pattern. PLoS Genetics. 18 sider.
- (2016). Circadian clock gene variants and insomnia, sleepiness, and shift work disorder. Sleep and Biological Rhythms. 55-62.
- (2015). Large-scale genomics unveil polygenic architecture of human cortical surface area. Nature Communications.
- (2015). Independent evidence for an association between general cognitive ability and a genetic locus for educational attainment. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 363-373.
- (2015). Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949). Molecular Psychiatry. 183-192.
- (2015). Genetic basis of a cognitive complexity metric. PLOS ONE.
- (2015). Common variants in the ARC gene are not associated with cognitive abilities. Brain and Behavior. 8 sider.
- (2015). Common genetic variants influence human subcortical brain structures. Nature. 224-229.
- (2014). The ENIGMA Consortium: Large-scale collaborative analyses of neuroimaging and genetic data. Brain Imaging and Behavior. 153-182.
- (2014). Molecular genetic evidence for overlap between general cognitive ability and risk for schizophrenia: A report from the Cognitive Genomics consorTium (COGENT). Molecular Psychiatry. 168-174.
- (2014). Lack of association of the rs1344706 ZNF804A variant with cognitive functions and DTI indices of white matter microstructure in two independent healthy populations. Psychiatry Research : Neuroimaging. 60-66.
- (2014). Human cognitive ability is influenced by genetic variation in components of postsynaptic signalling complexes assembled by NMDA receptors and MAGUK proteins. Translational Psychiatry.
- (2014). Genetic architecture of cognitive traits. Scandinavian Journal of Psychology. 255-262.
- (2014). GWAS-based pathway analysis differentiates between fluid and crystallized intelligence. Genes, Brain and Behavior.
- (2014). A possible genetic association with chronic fatigue in primary Sjögren’s syndrome: a candidate gene study. Rheumatology International. 191-197.
- (2014). A genome-wide association study of anorexia nervosa. Molecular Psychiatry. 1085-1094.
- (2013). No association of primary Sjögren's syndrome with Fcγ receptor gene variants. Genes and Immunity. 234-237.
- (2013). A genetic deconstruction of neurocognitive traits in schizophrenia and bipolar disorder. PLOS ONE. 9 sider.
- (2012). Linkage-disequilibrium-based binning affects the interpretation of GWASs. American Journal of Human Genetics. 727-733.
- (2012). Imaging and cognitive genetics: the Norwegian Cognitive NeuroGenetics Sample. Twin Research and Human Genetics. 442-452.
- (2012). Identification of common variants associated with human hippocampal and intracranial volumes. Nature Genetics. 552-561.
- (2012). Gene-based analysis of regionally enriched cortical genes in GWAS data sets of cognitive traits and psychiatric disorders. PLOS ONE. 14 sider.
- (2012). DCLK1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder. PLOS ONE. 12 sider.
- (2012). Association between genetic variants in the tumour necrosis factor/lymphotoxin alpha/lymphotoxin beta locus and primary Sjogren's syndrome in Scandinavian samples. Annals of the Rheumatic Diseases. 981-988.
- (2011). The Complement Control-Related Genes CSMD1 and CSMD2 Associate to Schizophrenia. Biological Psychiatry. 35-42.
- (2011). Potential association of muscarinic receptor 3 gene variants with primary Sjögren's syndrome. Annals of the Rheumatic Diseases. 1327-1329.
- (2011). Lipogenic effects of psychotropic drugs: focus on the SREBP system. Frontiers in Bioscience. 49-60.
- (2011). Genome-wide association studies establish that human intelligence is highly heritable and polygenic. Molecular Psychiatry. 996-1005.
- (2011). Association study of energy homeostasis genes and antipsychotic-induced weight gain in patients with schizophrenia. Pharmacopsychiatry. 15-20.
- (2010). Polymorphisms in SREBF1 and SREBF2, two antipsychotic-activated transcription factors controlling cellular lipogenesis, are associated with schizophrenia in German and Scandinavian samples. Molecular Psychiatry. 463-472.
- (2009). Variants in doublecortin- and calmodulin kinase like 1, a gene up-regulated by BDNF, are Associated with memory and general cognitive abilities. PLOS ONE.
- (2009). Association of MCTP2 gene variants with schizophrenia in three independent samples of Scandinavian origin (SCOPE). Psychiatry Research. 256-258.
- (2009). Association between the insulin-induced gene 2 (INSIG2) and weight gain in a German sample of antipsychotic-treated schizophrenic patients: perturbation of SREBP-controlled lipogenesis in drug-related metabolic adverse effects? Molecular Psychiatry. 308-317.
- (2009). A possible association between schizophrenia and GRIK3 polymorphisms in a multicenter sample of Scandinavian origin (SCOPE). Schizophrenia Research. 242-248.
- (2008). Polymorphisms in SREBF1 and SREBF2, two antipsychotic-activated transcription factors controlling cellular lipogenesis, are associated with schizophrenia in German and Scandinavian samples. Molecular Psychiatry.
- (2008). Association between the insulin-induced gene 2 (INSIG2) and weight gain in a German sample of antipsychotic-treated schizophrenic patients: pertubation of SREBP-controlled lipogenesis in drug-realted metabolic adverse effects? Molecular Psychiatry. 308-317.
- (2008). A possible association between schizophrenia and GRIK3 polymorphisms in a multicenter sample of Scandinavian origin (SCOPE). Schizophrenia Research.
Leserinnlegg
- (2018). Multi-Trait analysis of gwas and biological insights into cognition: A response to Hill (2018). Twin Research and Human Genetics. 394-397.
- (2012). Response to Zhu et al. American Journal of Human Genetics. 969-970.
- (2012). Linkage-Disequilibrium-Based Binning Misleads the Interpretation of Genome-wide Association Studies Response. American Journal of Human Genetics. 969-970.
Doktorgradsavhandling
- (2019). Clinical and molecular effects of guanylate cyclase C-activation.
- (2018). An evolutionary epigenetics approach to schizophrenia.
- (2015). A genetic study of schizophrenia and bipolar disorder. A cognitive endophenotype approach.
Sammendrag/abstract
- (2013). Human cognitive ability is influenced by genetic variation in components of postsynaptic signaling complexes assembled by MAGUK proteins. Behavior Genetics. 521-522.
- (2012). No association of primary Sjögren's Syndrome with Fc gamma? Receptor gene variants. Scandinavian Journal of Immunology. 198-198.
- (2010). Fc gamma receptor IIA, IIIA and IIIB single nucleotide polymorphisms and Fc gamma receptor IIIB copy number variation: No association with primary Sjögren's syndrome. Scandinavian Journal of Rheumatology. 36-36.
Poster
- (2020). Epigenetic Effects of THC and CBD in Neuronal Stem Cells.
- (2011). Association between tumor necrosis factor, lymphotoxin alpha and beta genetic variants and primary Sjögren`s syndrome in Scandinavian samples.
- (2009). Fc receptor IIA, IIIA and IIIB single nucleotide polymorphisms and Fc receptor IIIB copy number variation: No association with primary Sjögren’s syndrome.
Errata
- (2020). Publisher Correction: Common brain disorders are associated with heritable patterns of apparent aging of the brain (Nature Neuroscience, (2019), 22, 10, (1617-1623), 10.1038/s41593-019-0471-7). Nature Neuroscience. 295.
- (2019). Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function (Nature Communications, (2018), 9, 1, (2098), 10.1038/s41467-018-04362-x). Nature Communications.
Vitenskapelig oversiktsartikkel/review
- (2012). The Imaging and Cognition Genetics Conference 2011, ICG 2011: A Meeting of Minds. Frontiers in Neuroscience.
Se fullstendig oversikt over publikasjoner i CRIStin.
See my ORCID page: https://orcid.org/0000-0002-8085-051X