期刊
NATURE NEUROSCIENCE
卷 21, 期 10, 页码 1482-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41593-018-0223-0
关键词
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资金
- NIH [U01 NS082157, R01AG057331]
- US Department of Defense
- Michael J. Fox Foundation (MJFF)
- Australia NHMRC [GNT1067350]
- NIA [P30 AG028383, P50 AG005134]
- UK Wellcome Trust Investigator award
- National Brain and Tissue Resource for Parkinson's Disease and Related Disorders [NINDS U24 NS072026]
- [U01MH103339]
- [U01MH103365]
- [U01MH103392]
- [U01MH103340]
- [U01MH103346]
- [R01MH105472]
- [R01MH094714]
- [R01MH105898]
- [R21MH102791]
- [R21MH105881]
- [R21MH103877]
- [P50MH106934]
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.
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