Fine-mapping genomic loci refines bipolar disorder risk genes.
Journal: medRxiv : the preprint server for health sciences
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Affiliated Institutions: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany. SUNY Downstate Health Sciences University. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, Republic of Korea. Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. 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. Department of Clinical Sciences, Psychiatry, Umeå, University Medical Faculty, Umeå, Sweden. Department of Psychiatry, Dalhousie University, Halifax, NS, Canada. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Department of Neurology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany. National Kapodistrian University of Athens, nd Department of Psychiatry, Attikon General Hospital, Athens, Greece. Department of Psychiatry, University of Münster, Münster, Germany. Medical University of Graz, Division of Psychiatry and Psychotherapeutic Medicine, Graz, Austria. Department of Quantitative Health Sciences Research, Mayo Clinic, Rochester, MN, USA. Center for Statistical Genetics and Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA. Instituto de Salud Carlos III, Biomedical Network Research Centre on Mental Health (CIBERSAM), Madrid, Spain. University of Newcastle, Newcastle, NSW, Australia. School of Clinical Medicine, Discipline of Psychiatry and Mental Health, University of New South Wales, Sydney, NSW, Australia. University of Queensland, Brisbane, QLD, Australia. Department of Biomedicine, University of Basel, Basel, Switzerland. Neuropsychiatric Genetics Research Group, Dept of Psychiatry and Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland. Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK. Institute for Translatiol Psychiatry, University of Münster, Münster, Germany. Institute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany. Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA. Neuroscience Research Australia, Sydney, NSW, Australia. Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Würzburg, Würzburg, Germany. Department of Psychological Sciences, University of Missouri, Columbia, MO, USA. Psychological Medicine, University of Worcester, Worcester, UK. Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania. Mental Health Department, University Regional Hospital, Biomedicine Institute (IBIMA), Málaga, Spain. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. University of Western Australia, Nedlands, WA, Australia. Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden. Department of Psychiatry, University of California San Diego, La Jolla, CA, USA. Department of Psychiatry and Psychotherapy, University of Marburg, Germany. ISGlobal, Barcelona, Spain. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Université Paris Est Créteil, INSERM, IMRB, Translational Neuropsychiatry, Créteil, France. Cancer Epidemiology and Prevention, M. Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland. SA MRC Unit on Risk and Resilience in Mental Disorders, Dept of Psychiatry, Stellenbosch University, Stellenbosch, South Africa. Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. National and Kapodistrian University of Athens, Medical School, Clinical Biochemistry Laboratory, Attikon General Hospital, Athens, Greece. Department of Psychiatry and Genetics Institute, University of Florida, Gainesville, FL, USA. Research Institute, Lindner Center of HOPE, Mason, OH, USA. Systems Genetics Working Group, Department of Genetics, Stellenbosch University, Stellenbosch, South Africa. Division of Psychiatry, University College London, London, UK. Psychiatric Clinic, Alexander University Hospital, Bulgaria. Discipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia. National Kapodistrian University of Athens, Medical School, Clinical Biochemistry Laboratory, Attikon General Hospital, Athens, Greece. Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany. Hudsolpha Institute for Biotechnology, Huntsville, AL, USA. Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany. Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA. University of Melbourne, VIC, Australia. Institute for Genomic Health, SUNY Downstate Medical Center College of Medicine, Brooklyn, NY, USA. University of Patras, School of Health Sciences, Department of Pharmacy, Laboratory of Pharmacogenomics and Individualized Therapy, Patras, Greece. Department of Psychiatry, Departmet of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland. Psychiatry, Harvard Medical School, Boston, MA, USA. National and Kapodistrian University of Athens, nd Department of Psychiatry, Attikon General Hospital, Athens, Greece. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy. Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA. SAMRC Unit on Risk and Resilience in Mental Disorders, Dept of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa. Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada. Department of Psychology, Emory University, Atlanta, GA, USA. Department of Psychiatry, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea. Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan. Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland. Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA. Social, Genetic and Developmental Psychiatry Centre, King's College London, London, UK.
Abstract summary
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 22 likely causal SNPs for BD. 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 BD. Convergent lines of evidence supported the roles of , and in BD. 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 and transferability of BD polygenic risk scores across ancestrally diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI).Authors & Co-authors: Koromina Ravi Panagiotaropoulou Schilder Humphrey Braun Bidgeli Chatzinakos Coombes Kim Liu Terao O 'Connell Adams Adolfsson Alda Alfredsson Andlauer Andreassen Antoniou Baune Bengesser Biernacka Boehnke Bosch Cairns Carr Casas Catts Cichon Corvin Craddock Dafnas Dalkner Dannlowski Degenhardt Di Florio Dikeos Fellendorf Ferentinos Forstner Forty Frye Fullerton Gawlik Gizer Gordon-Smith Green Grigoroiu-Serbanescu Guzman-Parra Hahn Henskens Hillert Jablensky Jones Jones Jonsson Kelsoe Kircher Kirov Kittel-Schneider Kogevinas Landén Leboyer Lenger Lissowska Lochner Loughland MacIntyre Martin Maratou Mathews Mayoral McElroy McGregor McIntosh McQuillin Michie Milanova Mitchell Moutsatsou Mowry Müller-Myhsok Myers Nenadić Nöthen O'Donovan O'Donovan Ophoff Owen Pantelis Pato Pato Patrinos Pawlak Perlis Porichi Posthuma Ramos-Quiroga Reif Reininghaus Ribasés Rietschel Schall Schulze Scott Scott Serretti Weickert Smoller Artigas Stein Streit Toma Tooney Vieta Vincent Waldman Weickert Witt Hong Ikeda Iwata Świątkowska Won Edenberg Ripke Raj Coleman Mullins
Study Outcome
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Citations : O’Connell K. S. & Coombes B. J. Genetic contributions to bipolar disorder: current status and future directions. Psychol. Med. 51, 2156–2167 (2021).Authors : 130
Identifiers
Doi : 2024.02.12.24302716SSN :