ArticleNature neuroscience2018
Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease.
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Article in Nature neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 61 papers.
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61citing papers in PubMed
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61 citing papers in PubMed.
- Multi-locus genetic dosage shapes cognitive disease progression in Parkinson's patients: 15-year meta-analysis of 24 cohorts.NPJ Parkinson's disease · 2026Article
- Single-cell eQTL mapping reveals convergent glial-neuronal risk architecture in Parkinson's disease.bioRxiv : the preprint server for biology · 2026Article
- Mendelian randomization facilitates identification of schizophrenia risk enhancer RNAs.Molecular psychiatry · 2026Article
- Integrating Long-Read Structural Variant Analysis with single-nucleus RNA-seq to Elucidate Gene Expression Effects in Disease.bioRxiv : the preprint server for biology · 2026Article
- Emerging roles of circular RNAs and enhancer RNAs: new insights into the development and management of neurodegenerative disorders.Biomarker research · 2026Review
- The emerging roles of long non-coding RNAs in the nervous system.Nature reviews. Neuroscience · 2025Review
- Article
- Genetic Analysis of the X Chromosome Associates Loci with Progression of Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Multi-omics machine learning classifier and blood transcriptomic signature of Parkinson's disease.Research square · 2025Article
- An integrative systems-biology approach defines mechanisms of Alzheimer's disease neurodegeneration.Nature communications · 2025Article
- Dissecting the Emerging Regulatory and Mechanistic Paradigms of Transcribed Conserved Non-Coding Elements in Breast Cancer.Biomolecules · 2025Article
- New Multiomic Studies Shed Light on Cellular Diversity and Neuronal Susceptibility in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025Review
- Active enhancers: recent research advances and insights into disease.Biology direct · 2024Review
- Transcriptome-Wide Profiling of Nascent RNA in Neurons with Enriched H3K27ac Signal Elevates eRNA Identification Efficiency.ACS chemical neuroscience · 2024Article
- Transcriptional pathobiology and multi-omics predictors for Parkinson's disease.bioRxiv : the preprint server for biology · 2024Article
- An Emerging Role for Enhancer RNAs in Brain Disorders.Neuromolecular medicine · 2024Review
- Neuronal MAPT expression is mediated by long-range interactions with cis-regulatory elements.American journal of human genetics · 2024Article
- Article
- Correlation between dietary factors and Parkinson's disease revealed by the analysis of Mendelian randomization.Frontiers in nutrition · 2024Article
- The non-specific lethal complex regulates genes and pathways genetically linked to Parkinson's disease.Brain : a journal of neurology · 2023Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
22 authors.
Xianjun DongPrecision Neurology Program, Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8052-9320
Zhixiang LiaoPrecision Neurology Program, Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
David GritschPrecision Neurology Program, Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
Yavor HadzhievInstitute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.ORCID http://orcid.org/0000-0002-1134-4904
Yunfei BaiPrecision Neurology Program, Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
Joseph J LocascioPrecision Neurology Program, Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
Boris GuennewigSydney Medical School, Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia.
Ganqiang LiuPrecision Neurology Program, Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
Cornelis BlauwendraatGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Tao WangPrecision Neurology Program, Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
Charles H AdlerDepartment of Neurology, Mayo Clinic, Scottsdale, AZ, USA.
John C HedreenHarvard Brain Tissue Resource Center, McLean Hospital, Harvard Medical School, Boston, MA, USA.
Richard L M FaullCentre for Brain Research, University of Auckland, Auckland, New Zealand.
Matthew P FroschC.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Boston, MA, USA.
Peter T NelsonSanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
Patrizia RizzuGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Antony A CooperDivision of Neuroscience, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
Peter HeutinkGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.ORCID http://orcid.org/0000-0001-5218-1737
Thomas G BeachBanner Sun Health Research Institute, Sun City, AZ, USA.
John S MattickDivision of Neuroscience, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-7680-7527
Ferenc MüllerInstitute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.ORCID http://orcid.org/0000-0002-0996-774X
Clemens R ScherzerPrecision Neurology Program, Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA. cscherzer@rics.bwh.harvard.edu.ORCID http://orcid.org/0000-0002-0567-9193
Funding
THE ROLE OF ADVANCED CAA IN ALZHEIMER'S DEMENTIAP50AG005134 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 1985 to 2018
$42.1MUniversity of Kentucky Alzheimer's Disease Core Center - Biomarker CoreP30AG028383 · NIA · UNIVERSITY OF KENTUCKY · PI SCHMITT, FREDERICK · 2006 to 2020
$23.3M Functional Genomics of Human Brain DevelopmentP50MH106934 · NIMH · YALE UNIVERSITY · PI SESTAN, NENAD · 2014 to 2019
$7.9MNational Brain and Tissue Resource for Parkinson's Disease and Related DisordersU24NS072026 · NINDS · BANNER SUN HEALTH RESEARCH INSTITUTE · PI BEACH, THOMAS G · 2011 to 2015
$7.8MCis-Regulatory Epigenome Mappings in SchizophreniaU01MH103392 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, SKLAR, PAMELA · 2014 to 2017
$7.6MTranscriptional and Epigenetic Signatures of Human Brain Development and AutismU01MH103339 · NIMH · YALE UNIVERSITY · PI SESTAN, NENAD, STATE, MATTHEW W. · 2014 to 2017
$6.5MIntegrative Multi-Omic Discovery of Proximal Mechanisms Driving Age-Dependent NeurodegenerationRF1AG057331 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI FEANY, MEL B, FRAENKEL, ERNEST · 2017 to 2017
$4.8MGenetic variants affect brain gene expression and risks of psychiatric disordersU01MH103340 · NIMH · UPSTATE MEDICAL UNIVERSITY · PI LIU, CHUNYU, RZHETSKY, ANDREY · 2014 to 2017
$4.3MRNA Sequencing of the Limbic System in Bipolar DisorderR01MH105898 · NIMH · JOHNS HOPKINS UNIVERSITY · PI HYDE, THOMAS MICHAEL, ZANDI, PETER P. · 2015 to 2018
$3.1MDecoding schizophrenia-From GWAS to functional regulatory variantsR01MH105472 · NIMH · DUKE UNIVERSITY · PI CRAWFORD, GREGORY E, SULLIVAN, PATRICK F · 2014 to 2017
$2.9MEpigenetic and Transcriptional Dysregulation in Autism Spectrum DisorderR01MH094714 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H · 2011 to 2015
$2.8MBiomarkers for early intervention in Parkinson diseaseU01NS082157 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI SCHERZER, CLEMENS R · 2012 to 2016
$2.5MNIA NIH HHS P30 AG028383NIA NIH HHS P50 AG005134NIA NIH HHS RF1 AG057331NIMH NIH HHS P50 MH106934NIMH NIH HHS R01 MH094714NIMH NIH HHS R01 MH105472NIMH NIH HHS R01 MH105898NIMH NIH HHS R21 MH102791NIMH NIH HHS R21 MH103877NIMH NIH HHS R21 MH105881NIMH NIH HHS U01 MH103339NIMH NIH HHS U01 MH103340NIMH NIH HHS U01 MH103346NIMH NIH HHS U01 MH103365NIMH NIH HHS U01 MH103392NINDS NIH HHS U01 NS082157NINDS NIH HHS U24 NS072026Wellcome Trust
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 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.
Indexed as
AnimalsBrainDopaminergic NeuronsEnhancer Elements, GeneticFemaleGene Expression RegulationGenetic VariationHumansMaleMental DisordersQuantitative Trait LociZebrafish
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.