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Expression quantitative trait loci in the developing human brain and their enrichment in neuropsychiatric disorders

O’Brien, Heath E and Hannon, Eilis and Hill, Matthew J and Toste, Carolina C and Robertson, Matthew J and Morgan, Joanne E and McLaughlin, Gemma and Lewis, Cathryn M and Schalkwyk, Leonard C and Hall, Lynsey S and Pardiñas, Antonio F and Owen, Michael J and O’Donovan, Michael C and Mill, Jonathan and Bray, Nicholas J (2018) 'Expression quantitative trait loci in the developing human brain and their enrichment in neuropsychiatric disorders.' Genome Biology, 19 (1). 194-. ISSN 1465-6906

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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.

Item Type: Article
Uncontrolled Keywords: Brain; Fetus; Humans; Genetic Predisposition to Disease; Genetic Markers; Chromosome Mapping; Bipolar Disorder; Schizophrenia; Gene Expression Regulation; Phenotype; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Female; Male; Genome-Wide Association Study; High-Throughput Nucleotide Sequencing
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 22 Nov 2018 16:22
Last Modified: 06 Jan 2022 13:55

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