1. Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease
- Author
-
Clemens R. Scherzer, Ganqiang Liu, Ferenc Müller, David Gritsch, Patrizia Rizzu, Peter T. Nelson, Xianjun Dong, Cornelis Blauwendraat, Boris Guennewig, John S. Mattick, Joseph J. Locascio, Yunfei Bai, Zhixiang Liao, Peter Heutink, Tao Wang, Matthew P. Frosch, Charles H. Adler, Yavor Hadzhiev, Thomas G. Beach, Richard L.M. Faull, John C. Hedreen, and Antony A. Cooper
- Subjects
Male ,0301 basic medicine ,Quantitative Trait Loci ,Enhancer RNAs ,Biology ,genetics [Mental Disorders] ,Genome ,Article ,03 medical and health sciences ,0302 clinical medicine ,pathology [Brain] ,Dopamine ,ddc:570 ,medicine ,Animals ,Humans ,physiology [Dopaminergic Neurons] ,Enhancer ,Zebrafish ,Regulation of gene expression ,genetics [Quantitative Trait Loci] ,Dopaminergic Neurons ,Mental Disorders ,General Neuroscience ,Brain ,Genetic Variation ,pathology [Mental Disorders] ,genetics [Enhancer Elements, Genetic] ,Human brain ,biology.organism_classification ,genetics [Genetic Variation] ,3. Good health ,Enhancer Elements, Genetic ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Expression quantitative trait loci ,Female ,Neuroscience ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Enhancers function as DNA logic gates and may control specialized functions of billions of neurons. Here we show a tailored program of noncoding genome elements active in situ in physiologically distinct dopamine neurons of the human brain. We found 71,022 transcribed noncoding elements, many of which were consistent with active enhancers and with regulatory mechanisms in zebrafish and mouse brains. Genetic variants associated with schizophrenia, addiction, and Parkinson’s dis- ease were enriched in these elements. Expression quantitative trait locus analysis revealed that Parkinson’s disease-associated variants on chromosome 17q21 cis-regulate the expression of an enhancer RNA in dopamine neurons. This study shows that enhancers in dopamine neurons link genetic variation to neuropsychiatric traits.
- Published
- 2018
- Full Text
- View/download PDF