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Fine-mapping genomic loci refines bipolar disorder risk genes
M. Koromina, A. Ravi, G. Panagiotaropoulou, BM. Schilder, J. Humphrey, A. Braun, T. Bidgeli, C. Chatzinakos, BJ. Coombes, J. Kim, X. Liu, C. Terao, KS. O'Connell, MJ. Adams, R. Adolfsson, M. Alda, L. Alfredsson, TFM. Andlauer, OA. Andreassen, A....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
Grantová podpora
R01 MH124839
NIMH NIH HHS - United States
S10 OD018522
NIH HHS - United States
S10 OD026880
NIH HHS - United States
NLK
ProQuest Central
od 1998-06-01 do Před 1 rokem
Health & Medicine (ProQuest)
od 1998-06-01 do Před 1 rokem
Psychology Database (ProQuest)
od 2023-01-01 do Před 1 rokem
- MeSH
- bipolární porucha * genetika MeSH
- celogenomová asociační studie metody MeSH
- genetická predispozice k nemoci * genetika MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé MeSH
- lokus kvantitativního znaku genetika MeSH
- mapování chromozomů * metody MeSH
- multifaktoriální dědičnost genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Bipolar disorder is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 bipolar disorder 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 bipolar disorder. We mapped these SNPs to genes and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci and results from rare variant exome sequencing in bipolar disorder. Convergent lines of evidence supported the roles of genes involved in neurotransmission and neurodevelopment, including SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, FKBP2, RASGRP1, FURIN, FES, MED24 and THRA among others in bipolar disorder. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance of bipolar disorder polygenic risk scores across diverse populations and present a high-throughput fine-mapping pipeline.
Analytic and Translational Genetics Unit Massachusetts General Hospital Boston MA USA
Biochemistry and Molecular Biology Indiana University School of Medicine Indianapolis IN USA
Centre for Human Genetics University of Marburg Marburg Germany
Centre for Precision Psychiatry University of Oslo Oslo Norway
Centro de Biología Molecular Severo Ochoa Universidad Autónoma de Madrid and CSIC Madrid Spain
Clinical Research Center Shizuoka General Hospital Shizuoka Japan
Department of Biomedicine University of Basel Basel Switzerland
Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden
Department of Clinical Sciences Psychiatry Umeå University Medical Faculty Umeå Sweden
Department of Environmental Epidemiology Nofer Institute of Occupational Medicine Lodz Poland
Department of Medical and Molecular Genetics Indiana University Indianapolis IN USA
Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
Department of Medicine and Surgery Kore University of Enna Enna Italy
Department of Mental Health Hospital Universitari Vall d ́Hebron Barcelona Spain
Department of Neuroscience Icahn School of Medicine at Mount Sinai New York City NY USA
Department of Neuroscience SUNY Upstate Medical University Syracuse NY USA
Department of Psychiatry and Addiction Medicine Assistance Publique Hôpitaux de Paris Paris France
Department of Psychiatry and Behavioral Sciences SUNY Upstate Medical University Syracuse NY USA
Department of Psychiatry and Forensic Medicine Universitat Autònoma de Barcelona Barcelona Spain
Department of Psychiatry and Genetics Institute University of Florida Gainesville FL USA
Department of Psychiatry and Neurobehavioural Science University College Cork Cork Ireland
Department of Psychiatry and Psychology Mayo Clinic Rochester MN USA
Department of Psychiatry and Psychotherapy Charité Universitätsmedizin Berlin Germany
Department of Psychiatry and Psychotherapy University Medical Center Göttingen Göttingen Germany
Department of Psychiatry and Psychotherapy University of Marburg Marburg Germany
Department of Psychiatry Dalhousie University Halifax Nova Scotia Canada
Department of Psychiatry Fujita Health University School of Medicine Toyoake Japan
Department of Psychiatry Icahn School of Medicine at Mount Sinai New York City NY USA
Department of Psychiatry Massachusetts General Hospital Boston MA USA
Department of Psychiatry University of British Columbia Vancouver British Columbia Canada
Department of Psychiatry University of California San Diego La Jolla CA USA
Department of Psychiatry University of Melbourne Melbourne Victoria Australia
Department of Psychiatry University of Münster Münster Germany
Department of Psychiatry University of North Carolina at Chapel Hill Chapel Hill NC USA
Department of Psychological Sciences University of Missouri Columbia MO USA
Department of Psychology Emory University Atlanta GA USA
Department of Quantitative Health Sciences Mayo Clinic Rochester MN USA
Department of Translational Research in Psychiatry Max Planck Institute of Psychiatry Munich Germany
Division of Clinical Research Massachusetts General Hospital Boston MA USA
Division of Mental Health and Addiction Oslo University Hospital Oslo Norway
Division of Psychiatry Centre for Clinical Brain Sciences The University of Edinburgh Edinburgh UK
Division of Psychiatry University College London London UK
Functional Genomics Laboratory School of Medicine University of California Irvine Irvine CA USA
German Center for Mental Health partner site Mannheim Heidelberg Ulm Heidelberg Germany
HudsonAlpha Institute for Biotechnology Huntsville AL USA
Indiana University School of Medicine Indianapolis IN USA
Institute for Genomic Health SUNY Downstate Medical Center College of Medicine Brooklyn NY USA
Institute for Translational Psychiatry University of Münster Münster Germany
Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden
Institute of Medical Genetics and Pathology University Hospital Basel Basel Switzerland
Institute of Neuroscience and Medicine Research Centre Jülich Jülich Germany
Institute of Neuroscience and Physiology University of Gothenburg Gothenburg Sweden
Institute of Psychiatric Phenomics and Genomics University Hospital LMU Munich Munich Germany
Instituto de Salud Carlos 3 Biomedical Network Research Centre on Mental Health Madrid Spain
Medical University of Graz Division of Psychiatry and Psychotherapeutic Medicine Graz Austria
Mental Health Department University Regional Hospital Biomedicine Institute Málaga Spain
Munich Cluster for Systems Neurology Munich Germany
National Institute of Mental Health Klecany Czech Republic
Neuroscience Research Australia Sydney New South Wales Australia
NIHR Maudsley Biomedical Research Centre South London and Maudsley NHS Foundation Trust London UK
Oasi Research Institute IRCCS Troina Italy
Psychiatric and Neurodevelopmental Genetics Unit Massachusetts General Hospital Boston MA USA
Psychiatry Harvard Medical School Boston MA USA
Psychological Medicine University of Worcester Worcester UK
Research Institute Lindner Center of HOPE Mason OH USA
School of Psychology The University of Queensland Brisbane Queensland Australia
Social Genetic and Developmental Psychiatry Centre King's College London London UK
Stanley Center for Psychiatric Research Broad Institute Cambridge MA USA
Stark Neurosciences Research Institute Indiana University School of Medicine Indianapolis IN USA
SUNY Downstate Health Sciences University Brooklyn NY USA
University of Newcastle Newcastle New South Wales Australia
University of Paris Est Créteil INSERM IMRB Translatiol Neuropsychiatry Créteil France
University of Queensland Brisbane Queensland Australia
University of Western Australia Nedlands Western Australia Australia
Zayed Center for Health Sciences United Arab Emirates University Al Ain United Arab Emirates
Citace poskytuje Crossref.org
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- 700 1_
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