ZFIN ID: ZDB-PUB-180919-5
Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease
Dong, X., Liao, Z., Gritsch, D., Hadzhiev, Y., Bai, Y., Locascio, J.J., Guennewig, B., Liu, G., Blauwendraat, C., Wang, T., Adler, C.H., Hedreen, J.C., Faull, R.L.M., Frosch, M.P., Nelson, P.T., Rizzu, P., Cooper, A.A., Heutink, P., Beach, T.G., Mattick, J.S., Müller, F., Scherzer, C.R.
Date: 2018
Source: Nature Neuroscience   21(10): 1482-1492 (Journal)
Registered Authors: Hadzhiev, Yavor, Müller, Ferenc
Keywords: none
MeSH Terms:
  • Animals
  • Brain/pathology*
  • Dopaminergic Neurons/physiology*
  • Enhancer Elements, Genetic/genetics
  • Female
  • Gene Expression Regulation
  • Genetic Variation/genetics*
  • Humans
  • Male
  • Mental Disorders/genetics*
  • Mental Disorders/pathology*
  • Quantitative Trait Loci/genetics*
  • Zebrafish
PubMed: 30224808 Full text @ Nat. Neurosci.
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 disease 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.