Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic...
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| Vydáno v: | Nature genetics Ročník 53; číslo 6; s. 817 - 829 |
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| Médium: | Journal Article |
| Jazyk: | angličtina |
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New York
Nature Publishing Group US
01.06.2021
Nature Publishing Group |
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| ISSN: | 1061-4036, 1546-1718, 1546-1718 |
| On-line přístup: | Získat plný text |
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| Abstract | Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing. |
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| AbstractList | Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing. Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing. Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. |
| Audience | Academic |
| Author | Hougaard, David M. Strauss, John S. Nievergelt, Caroline M. Beins, Eva C. Lochner, Christine Mors, Ole Terao, Chikashi Wray, Naomi R. Bybjerg-Grauholm, Jonas Witt, Stephanie H. Dikeos, Dimitris Boks, Marco P. Rivas, Fabio Vieta, Eduard Zandi, Peter P. Adolfsson, Rolf Smoller, Jordan W. Scott, Rodney J. Jablensky, Assen V. Stein, Dan J. MacIntyre, Donald J. Hveem, Kristian Mathews, Carol A. Awasthi, Swapnil Sánchez-Mora, Cristina Douzenis, Athanassios Herms, Stefan Gizer, Ian R. Potash, James B. Tsermpini, Evangelia-Eirini Kushner, Steven A. Mattheisen, Manuel Moran, Jennifer L. Hauser, Joanna Degenhardt, Franziska O’Brien, Niamh Mowry, Bryan Papiol, Sergi Catts, Stanley Ferentinos, Panagiotis O’Connell, Kevin S. Hillert, Jan O’Donovan, Michael C. Escott-Price, Valentina Leboyer, Marion Craddock, Nicholas Budde, Monika Gordon, Scott D. Cervantes, Pablo Martin, Nicholas G. Baune, Bernhard T. Olsson, Tomas Forstner, Andreas J. Zillich, Lea Als, Thomas D. Adorjan, Kristina Ferrier, I. Nicol Spijker, Anne T. Stordal, Eystein Kennedy, James L. Grigor |
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| Snippet | Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549... |
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| SubjectTerms | 45 45/43 631/208/205/2138 692/699/476/1333 Agriculture Anesthetics Animal Genetics and Genomics Antipsychotics Biomedical and Life Sciences Biomedicine Bipolar Disorder Bipolar Disorder - genetics Calcium Calcium channel blockers Calcium channels Cancer Research Case-Control Studies Chromosomes, Human Chromosomes, Human - genetics Consortia Diagnosis educational-attainment Etiology Furin Gene expression Gene Function Gene loci Gene mapping Genes Genetic aspects Genetic Predisposition to Disease Genetics & Heredity Genome, Human Genome-wide association studies Genome-Wide Association Study Genomes Genomics genotype imputation Human Genetics Human health and pathology Humans identification ld score regression Life Sciences loci Major Histocompatibility Complex Major Histocompatibility Complex - genetics Mental disorders Meta-analysis Multifactorial Inheritance Multifactorial Inheritance - genetics Neurosciences Neurovetenskaper Phenotype polygenicity Population Prefrontal cortex prevalence Psychiatrics and mental health Psychotropic drugs Quantitative Trait Loci Quantitative Trait Loci - genetics risk Risk Factors schizophrenia spectrum disorder |
| Title | Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology |
| URI | https://link.springer.com/article/10.1038/s41588-021-00857-4 https://www.ncbi.nlm.nih.gov/pubmed/34002096 https://www.proquest.com/docview/2540566045 https://www.proquest.com/docview/2528814149 https://inserm.hal.science/inserm-03854548 https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-186261 https://gup.ub.gu.se/publication/305448 http://kipublications.ki.se/Default.aspx?queryparsed=id:146695436 |
| Volume | 53 |
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