Expression quantitative trait loci in the developing human brain and their enrichment in neuropsychiatric disorders
dc.contributor.author | O'Brien, HE | |
dc.contributor.author | Hannon, E | |
dc.contributor.author | Hill, MJ | |
dc.contributor.author | Toste, CC | |
dc.contributor.author | Robertson, MJ | |
dc.contributor.author | Morgan, JE | |
dc.contributor.author | McLaughlin, G | |
dc.contributor.author | Lewis, CM | |
dc.contributor.author | Schalkwyk, LC | |
dc.contributor.author | Hall, LS | |
dc.contributor.author | Pardiñas, AF | |
dc.contributor.author | Owen, MJ | |
dc.contributor.author | O'Donovan, MC | |
dc.contributor.author | Mill, J | |
dc.contributor.author | Bray, NJ | |
dc.date.accessioned | 2019-01-03T14:25:37Z | |
dc.date.issued | 2018-11-12 | |
dc.description.abstract | BACKGROUND: Genetic influences on gene expression in the human fetal brain plausibly impact upon a variety of postnatal brain-related traits, including susceptibility to neuropsychiatric disorders. However, to date, there have been no studies that have mapped genome-wide expression quantitative trait loci (eQTL) specifically in the human prenatal brain. RESULTS: We performed deep RNA sequencing and genome-wide genotyping on a unique collection of 120 human brains from the second trimester of gestation to provide the first eQTL dataset derived exclusively from the human fetal brain. We identify high confidence cis-acting eQTL at the individual transcript as well as whole gene level, including many mapping to a common inversion polymorphism on chromosome 17q21. Fetal brain eQTL are enriched among risk variants for postnatal conditions including attention deficit hyperactivity disorder, schizophrenia, and bipolar disorder. We further identify changes in gene expression within the prenatal brain that potentially mediate risk for neuropsychiatric traits, including increased expression of C4A in association with genetic risk for schizophrenia, increased expression of LRRC57 in association with genetic risk for bipolar disorder, and altered expression of multiple genes within the chromosome 17q21 inversion in association with variants influencing the personality trait of neuroticism. CONCLUSIONS: We have mapped eQTL operating in the human fetal brain, providing evidence that these confer risk to certain neuropsychiatric disorders, and identifying gene expression changes that potentially mediate susceptibility to these conditions. | en_GB |
dc.description.sponsorship | Medical Research Council | en_GB |
dc.identifier.citation | Vol. 19, article 194 | en_GB |
dc.identifier.doi | 10.1186/s13059-018-1567-1 | |
dc.identifier.grantnumber | MR/L010674/2 | en_GB |
dc.identifier.grantnumber | MR/L010305/1 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/35330 | |
dc.language.iso | en | en_GB |
dc.publisher | BMC | en_GB |
dc.rights | © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated | en_GB |
dc.title | Expression quantitative trait loci in the developing human brain and their enrichment in neuropsychiatric disorders | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-01-03T14:25:37Z | |
dc.description | This is the final version. Available on open access from BMC via the DOI in this record | en_GB |
dc.description | Availability of data and materials: The eQTL summary statistics data generated and analyzed in the current study are available in the figshare repository https://doi.org/10.6084/m9.figshare.6881825 Individual RNA-Seq FASTQ files are available through the European Genome-phenome Archive (https://ega-archive.org) under study accession EGAS00001003214 | en_GB |
dc.identifier.journal | Genome Biology | en_GB |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2018-10-18 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2018-11-12 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-01-03T14:22:43Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2019-01-03T14:25:53Z | |
refterms.panel | A | en_GB |
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(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated