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Genome Biol. 2018 Nov 12;19(1):194. doi: 10.1186/s13059-018-1567-1.

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

Author information

1
MRC Centre for Neuropsychiatric Genetics & Genomics, Division of Psychological Medicine & Clinical Neurosciences, Cardiff University, Cardiff, UK.
2
University of Exeter Medical School, University of Exeter, Exeter, UK.
3
Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
4
School of Biological Sciences, University of Essex, Colchester, UK.
5
MRC Centre for Neuropsychiatric Genetics & Genomics, Division of Psychological Medicine & Clinical Neurosciences, Cardiff University, Cardiff, UK. BrayN3@Cardiff.ac.uk.
6
MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff University School of Medicine, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK. BrayN3@Cardiff.ac.uk.

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.

PMID:
30419947
PMCID:
PMC6231252
DOI:
10.1186/s13059-018-1567-1
[Indexed for MEDLINE]
Free PMC Article

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