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Stephanie Le Hellard's picture

Stephanie Le Hellard

Professor, Human Genetics
  • E-mailStephanie.LeHellard@uib.no
  • Phone+47 900 58 089
  • Visitor Address
    Labbygget, 5th floor
    Bergen
    Room 
    5310
  • Postal Address
    Postboks 7804
    5020 Bergen

The aim of my research group is to identify how different layers of genetics, epigenetics and gene expression can be involved together in the development of mental disorders, their outcome and how they are modulated by the environment.

I am a core researcher at the NORMENT, a Norwegian Centre of Excellence for Research on Mental Health. The NORMENT is described here: http://www.med.uio.no/norment/english/ In Bergen I am situated at the Dr Martens group for research on biological psychiatry, our research activity is described here: http://www.uib.no/en/rg/geneticsgroup/106397/martens-group#at-a-glance

Description of our group in the NORMENT centre:

Epigenetics and multi-omics

About the group

The group consists of people with background in genetics, statistics, medicine and informatics who together bring their complementary expertise to try understand the interaction between genetic and environmental risk in mental disorders. We work in close collaboration with clinicians.

We use datasets generated in house or publicly available that combine genetic, epigenetic and gene expression datasets for mental disorders (mostly schizophrenia and bipolar disorders) that are in addition well annotated for environmental factors.

Aims

Genetic studies of psychiatric disorders have identified numerous genomic regions that harbor genetic variants which explain some of the risk to develop illness. In addition to the genetic risk, many environmental risks (drug use, trauma, migration, etc) can affect the development and the outcome of mental disorders.

Our aim is to identify how the different layers of genetics, epigenetics and gene expression can be involved together in the development of mental disorders, their outcome and how they are modulated by the environment.

Projects
  • Molecular mechanisms of exposure to cannabis in patients with schizophrenia: We are looking at the difference between cannabis users and non users in DNA methylation and modelling these differences in cell models.
  • The 3D sample: In a set of patients and controls we have genetic information, epigenetic information and gene expression. We are combining these 3 datasets to try identify common effects across the 3 dimensions.
  • DNA methylation in psychiatric disorders, and mediation of gene by environment effects, from birth to adulthood. We are examining the variations on DNA methylation associated with mental disorders.
  • An evolutionary epigenetics approach to schizophrenia: We examine if regions differentially methylated in the recent human evolution can be implicated in schizophrenia.
Selected publications
  • van der Meer D, et al. (2018) Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes. Mol Psychiatry.
  • Banerjee N, et al. (2018) Recently evolved human-specific methylated regions are enriched in schizophrenia signals. Bmc Evol Biol 18.
  • Hughes T, et al. (2018) Elevated expression of a minor isoform of ANK3 is a risk factor for bipolar disorder. Transl Psychiatry 8(1):210.
  • Banerjee N, et al. (2018) Analysis of differentially methylated regions in great apes and extinct hominids provides support for the evolutionary hypothesis of schizophrenia. Schizophr Res.
  • Davies G, et al. (2018) Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. Nature Communications 9.

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. http://www.uib.no/en/course/HUMGEN301

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.

 

Academic article
  • 2020. Shared genetic risk between eating disorder‐ and substance‐use‐related phenotypes: Evidence from genome‐wide association studies. Addiction Biology. 21 pages.
  • 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 pages.
  • 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 pages.
  • 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 pages.
  • 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 pages.
  • 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 pages.
  • 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 pages.
  • 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 pages.
  • 2012. DCLK1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder. PLOS ONE. 12 pages.
  • 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.
Reader opinion piece
  • 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.
Doctoral dissertation
  • 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.
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
  • 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.
Academic literature review
  • 2012. The Imaging and Cognition Genetics Conference 2011, ICG 2011: A Meeting of Minds.

More information in national current research information system (CRIStin)

See my ORCID page:  https://orcid.org/0000-0002-8085-051X

Phd

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