A genome-wide association study of shared risk across psychiatric disorders implicates gene regulation during fetal neurodevelopment. Schork, A. J., Won, H., Appadurai, V., Nudel, R., Gandal, M., Delaneau, O., Revsbech Christiansen, M., Hougaard, D. M., Bækved-Hansen, M., Bybjerg-Grauholm, J., Giørtz Pedersen, M., Agerbo, E., Bøcker Pedersen, C., Neale, B. M., Daly, M. J., Wray, N. R., Nordentoft, M., Mors, O., Børglum, A. D., Bo Mortensen, P., Buil, A., Thompson, W. K., Geschwind, D. H., & Werge, T. Nature Neuroscience, 22(3):353–361, 2019. 00000 doi abstract bibtex There is mounting evidence that seemingly diverse psychiatric disorders share genetic etiology, but the biological substrates mediating this overlap are not well characterized. Here we leverage the unique Integrative Psychiatric Research Consortium (iPSYCH) study, a nationally representative cohort ascertained through clinical psychiatric diagnoses indicated in Danish national health registers. We confirm previous reports of individual and cross-disorder single-nucleotide polymorphism heritability for major psychiatric disorders and perform a cross-disorder genome-wide association study. We identify four novel genome-wide significant loci encompassing variants predicted to regulate genes expressed in radial glia and interneurons in the developing neocortex during mid-gestation. This epoch is supported by partitioning cross-disorder single-nucleotide polymorphism heritability, which is enriched at regulatory chromatin active during fetal neurodevelopment. These findings suggest that dysregulation of genes that direct neurodevelopment by common genetic variants may result in general liability for many later psychiatric outcomes.
@article{schork_genome-wide_2019,
title = {A genome-wide association study of shared risk across psychiatric disorders implicates gene regulation during fetal neurodevelopment},
volume = {22},
issn = {1546-1726},
doi = {10.1038/s41593-018-0320-0},
abstract = {There is mounting evidence that seemingly diverse psychiatric disorders share genetic etiology, but the biological substrates mediating this overlap are not well characterized. Here we leverage the unique Integrative Psychiatric Research Consortium (iPSYCH) study, a nationally representative cohort ascertained through clinical psychiatric diagnoses indicated in Danish national health registers. We confirm previous reports of individual and cross-disorder single-nucleotide polymorphism heritability for major psychiatric disorders and perform a cross-disorder genome-wide association study. We identify four novel genome-wide significant loci encompassing variants predicted to regulate genes expressed in radial glia and interneurons in the developing neocortex during mid-gestation. This epoch is supported by partitioning cross-disorder single-nucleotide polymorphism heritability, which is enriched at regulatory chromatin active during fetal neurodevelopment. These findings suggest that dysregulation of genes that direct neurodevelopment by common genetic variants may result in general liability for many later psychiatric outcomes.},
language = {eng},
number = {3},
journal = {Nature Neuroscience},
author = {Schork, Andrew J. and Won, Hyejung and Appadurai, Vivek and Nudel, Ron and Gandal, Mike and Delaneau, Olivier and Revsbech Christiansen, Malene and Hougaard, David M. and Bækved-Hansen, Marie and Bybjerg-Grauholm, Jonas and Giørtz Pedersen, Marianne and Agerbo, Esben and Bøcker Pedersen, Carsten and Neale, Benjamin M. and Daly, Mark J. and Wray, Naomi R. and Nordentoft, Merete and Mors, Ole and Børglum, Anders D. and Bo Mortensen, Preben and Buil, Alfonso and Thompson, Wesley K. and Geschwind, Daniel H. and Werge, Thomas},
year = {2019},
pmid = {30692689},
pmcid = {PMC6497521},
note = {00000 },
keywords = {Brain, Cohort Studies, Female, Gene Expression Regulation, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Mental Disorders, Polymorphism, Single Nucleotide, Risk Factors},
pages = {353--361}
}
Downloads: 0
{"_id":"4MsqYG73LETYNQcMT","bibbaseid":"schork-won-appadurai-nudel-gandal-delaneau-revsbechchristiansen-hougaard-etal-agenomewideassociationstudyofsharedriskacrosspsychiatricdisordersimplicatesgeneregulationduringfetalneurodevelopment-2019","authorIDs":[],"author_short":["Schork, A. J.","Won, H.","Appadurai, V.","Nudel, R.","Gandal, M.","Delaneau, O.","Revsbech Christiansen, M.","Hougaard, D. M.","Bækved-Hansen, M.","Bybjerg-Grauholm, J.","Giørtz Pedersen, M.","Agerbo, E.","Bøcker Pedersen, C.","Neale, B. M.","Daly, M. J.","Wray, N. R.","Nordentoft, M.","Mors, O.","Børglum, A. D.","Bo Mortensen, P.","Buil, A.","Thompson, W. K.","Geschwind, D. H.","Werge, T."],"bibdata":{"bibtype":"article","type":"article","title":"A genome-wide association study of shared risk across psychiatric disorders implicates gene regulation during fetal neurodevelopment","volume":"22","issn":"1546-1726","doi":"10.1038/s41593-018-0320-0","abstract":"There is mounting evidence that seemingly diverse psychiatric disorders share genetic etiology, but the biological substrates mediating this overlap are not well characterized. Here we leverage the unique Integrative Psychiatric Research Consortium (iPSYCH) study, a nationally representative cohort ascertained through clinical psychiatric diagnoses indicated in Danish national health registers. We confirm previous reports of individual and cross-disorder single-nucleotide polymorphism heritability for major psychiatric disorders and perform a cross-disorder genome-wide association study. We identify four novel genome-wide significant loci encompassing variants predicted to regulate genes expressed in radial glia and interneurons in the developing neocortex during mid-gestation. This epoch is supported by partitioning cross-disorder single-nucleotide polymorphism heritability, which is enriched at regulatory chromatin active during fetal neurodevelopment. These findings suggest that dysregulation of genes that direct neurodevelopment by common genetic variants may result in general liability for many later psychiatric outcomes.","language":"eng","number":"3","journal":"Nature Neuroscience","author":[{"propositions":[],"lastnames":["Schork"],"firstnames":["Andrew","J."],"suffixes":[]},{"propositions":[],"lastnames":["Won"],"firstnames":["Hyejung"],"suffixes":[]},{"propositions":[],"lastnames":["Appadurai"],"firstnames":["Vivek"],"suffixes":[]},{"propositions":[],"lastnames":["Nudel"],"firstnames":["Ron"],"suffixes":[]},{"propositions":[],"lastnames":["Gandal"],"firstnames":["Mike"],"suffixes":[]},{"propositions":[],"lastnames":["Delaneau"],"firstnames":["Olivier"],"suffixes":[]},{"propositions":[],"lastnames":["Revsbech","Christiansen"],"firstnames":["Malene"],"suffixes":[]},{"propositions":[],"lastnames":["Hougaard"],"firstnames":["David","M."],"suffixes":[]},{"propositions":[],"lastnames":["Bækved-Hansen"],"firstnames":["Marie"],"suffixes":[]},{"propositions":[],"lastnames":["Bybjerg-Grauholm"],"firstnames":["Jonas"],"suffixes":[]},{"propositions":[],"lastnames":["Giørtz","Pedersen"],"firstnames":["Marianne"],"suffixes":[]},{"propositions":[],"lastnames":["Agerbo"],"firstnames":["Esben"],"suffixes":[]},{"propositions":[],"lastnames":["Bøcker","Pedersen"],"firstnames":["Carsten"],"suffixes":[]},{"propositions":[],"lastnames":["Neale"],"firstnames":["Benjamin","M."],"suffixes":[]},{"propositions":[],"lastnames":["Daly"],"firstnames":["Mark","J."],"suffixes":[]},{"propositions":[],"lastnames":["Wray"],"firstnames":["Naomi","R."],"suffixes":[]},{"propositions":[],"lastnames":["Nordentoft"],"firstnames":["Merete"],"suffixes":[]},{"propositions":[],"lastnames":["Mors"],"firstnames":["Ole"],"suffixes":[]},{"propositions":[],"lastnames":["Børglum"],"firstnames":["Anders","D."],"suffixes":[]},{"propositions":[],"lastnames":["Bo","Mortensen"],"firstnames":["Preben"],"suffixes":[]},{"propositions":[],"lastnames":["Buil"],"firstnames":["Alfonso"],"suffixes":[]},{"propositions":[],"lastnames":["Thompson"],"firstnames":["Wesley","K."],"suffixes":[]},{"propositions":[],"lastnames":["Geschwind"],"firstnames":["Daniel","H."],"suffixes":[]},{"propositions":[],"lastnames":["Werge"],"firstnames":["Thomas"],"suffixes":[]}],"year":"2019","pmid":"30692689","pmcid":"PMC6497521","note":"00000 ","keywords":"Brain, Cohort Studies, Female, Gene Expression Regulation, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Mental Disorders, Polymorphism, Single Nucleotide, Risk Factors","pages":"353–361","bibtex":"@article{schork_genome-wide_2019,\n\ttitle = {A genome-wide association study of shared risk across psychiatric disorders implicates gene regulation during fetal neurodevelopment},\n\tvolume = {22},\n\tissn = {1546-1726},\n\tdoi = {10.1038/s41593-018-0320-0},\n\tabstract = {There is mounting evidence that seemingly diverse psychiatric disorders share genetic etiology, but the biological substrates mediating this overlap are not well characterized. Here we leverage the unique Integrative Psychiatric Research Consortium (iPSYCH) study, a nationally representative cohort ascertained through clinical psychiatric diagnoses indicated in Danish national health registers. We confirm previous reports of individual and cross-disorder single-nucleotide polymorphism heritability for major psychiatric disorders and perform a cross-disorder genome-wide association study. We identify four novel genome-wide significant loci encompassing variants predicted to regulate genes expressed in radial glia and interneurons in the developing neocortex during mid-gestation. This epoch is supported by partitioning cross-disorder single-nucleotide polymorphism heritability, which is enriched at regulatory chromatin active during fetal neurodevelopment. These findings suggest that dysregulation of genes that direct neurodevelopment by common genetic variants may result in general liability for many later psychiatric outcomes.},\n\tlanguage = {eng},\n\tnumber = {3},\n\tjournal = {Nature Neuroscience},\n\tauthor = {Schork, Andrew J. and Won, Hyejung and Appadurai, Vivek and Nudel, Ron and Gandal, Mike and Delaneau, Olivier and Revsbech Christiansen, Malene and Hougaard, David M. and Bækved-Hansen, Marie and Bybjerg-Grauholm, Jonas and Giørtz Pedersen, Marianne and Agerbo, Esben and Bøcker Pedersen, Carsten and Neale, Benjamin M. and Daly, Mark J. and Wray, Naomi R. and Nordentoft, Merete and Mors, Ole and Børglum, Anders D. and Bo Mortensen, Preben and Buil, Alfonso and Thompson, Wesley K. and Geschwind, Daniel H. and Werge, Thomas},\n\tyear = {2019},\n\tpmid = {30692689},\n\tpmcid = {PMC6497521},\n\tnote = {00000 },\n\tkeywords = {Brain, Cohort Studies, Female, Gene Expression Regulation, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Mental Disorders, Polymorphism, Single Nucleotide, Risk Factors},\n\tpages = {353--361}\n}\n\n","author_short":["Schork, A. J.","Won, H.","Appadurai, V.","Nudel, R.","Gandal, M.","Delaneau, O.","Revsbech Christiansen, M.","Hougaard, D. M.","Bækved-Hansen, M.","Bybjerg-Grauholm, J.","Giørtz Pedersen, M.","Agerbo, E.","Bøcker Pedersen, C.","Neale, B. M.","Daly, M. J.","Wray, N. R.","Nordentoft, M.","Mors, O.","Børglum, A. D.","Bo Mortensen, P.","Buil, A.","Thompson, W. K.","Geschwind, D. H.","Werge, T."],"key":"schork_genome-wide_2019","id":"schork_genome-wide_2019","bibbaseid":"schork-won-appadurai-nudel-gandal-delaneau-revsbechchristiansen-hougaard-etal-agenomewideassociationstudyofsharedriskacrosspsychiatricdisordersimplicatesgeneregulationduringfetalneurodevelopment-2019","role":"author","urls":{},"keyword":["Brain","Cohort Studies","Female","Gene Expression Regulation","Genetic Loci","Genetic Predisposition to Disease","Genome-Wide Association Study","Humans","Male","Mental Disorders","Polymorphism","Single Nucleotide","Risk Factors"],"downloads":0},"bibtype":"article","biburl":"https://bibbase.org/zotero/mgandal","creationDate":"2019-07-07T17:19:49.111Z","downloads":0,"keywords":["brain","cohort studies","female","gene expression regulation","genetic loci","genetic predisposition to disease","genome-wide association study","humans","male","mental disorders","polymorphism","single nucleotide","risk factors"],"search_terms":["genome","wide","association","study","shared","risk","psychiatric","disorders","implicates","gene","regulation","during","fetal","neurodevelopment","schork","won","appadurai","nudel","gandal","delaneau","revsbech christiansen","hougaard","bækved-hansen","bybjerg-grauholm","giørtz pedersen","agerbo","bøcker pedersen","neale","daly","wray","nordentoft","mors","børglum","bo mortensen","buil","thompson","geschwind","werge"],"title":"A genome-wide association study of shared risk across psychiatric disorders implicates gene regulation during fetal neurodevelopment","year":2019,"dataSources":["iSYPWjNRYqB7Q3Fgn"]}