{"id":"https://openalex.org/W4414599325","doi":"https://doi.org/10.1101/2025.09.09.674964","title":"Redefining Parkinson's Disease by Dysregulated Genetic Networks in Distinct Cell Types","display_name":"Redefining Parkinson's Disease by Dysregulated Genetic Networks in Distinct Cell Types","publication_year":2025,"publication_date":"2025-09-13","ids":{"openalex":"https://openalex.org/W4414599325","doi":"https://doi.org/10.1101/2025.09.09.674964"},"language":"en","primary_location":{"id":"doi:10.1101/2025.09.09.674964","doi":"https://doi.org/10.1101/2025.09.09.674964","is_oa":true,"landing_page_url":"https://doi.org/10.1101/2025.09.09.674964","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://doi.org/10.1101/2025.09.09.674964","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":null,"display_name":"Jane Yang","orcid":"https://orcid.org/0000-0003-0114-5503","observed_orcids":["https://orcid.org/0000-0003-0114-5503"]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Jane Yang","raw_affiliation_strings":["Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA"],"raw_orcid":"https://orcid.org/0000-0003-0114-5503","affiliations":[{"raw_affiliation_string":"Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA","institution_ids":["https://openalex.org/I36258959"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046321194","display_name":"Arianna Colini Baldeschi","orcid":"https://orcid.org/0000-0002-8638-3705","observed_orcids":["https://orcid.org/0000-0002-8638-3705"]},"institutions":[{"id":"https://openalex.org/I1317189400","display_name":"Van Andel Institute","ror":"https://ror.org/00wm07d60","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I1317189400"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Arianna Colini Baldeschi","raw_affiliation_strings":["Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA","institution_ids":["https://openalex.org/I1317189400"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5042502199","display_name":"JungHo Kong","orcid":"https://orcid.org/0000-0002-3532-3163","observed_orcids":["https://orcid.org/0000-0002-3532-3163"]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"JungHo Kong","raw_affiliation_strings":["Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA","institution_ids":["https://openalex.org/I36258959"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5040431101","display_name":"Nicole M. Mattson","orcid":"https://orcid.org/0000-0001-5881-3387","observed_orcids":["https://orcid.org/0000-0001-5881-3387"]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Nicole Mattson","raw_affiliation_strings":["Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA","institution_ids":["https://openalex.org/I36258959"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5085505904","display_name":"Erin C Schiksnis","orcid":"https://orcid.org/0000-0003-2756-8168","observed_orcids":["https://orcid.org/0000-0003-2756-8168"]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Erin Schiksnis","raw_affiliation_strings":["Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA","institution_ids":["https://openalex.org/I36258959"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5003354181","display_name":"Sarah N. Wright","orcid":"https://orcid.org/0000-0003-3441-5469","observed_orcids":["https://orcid.org/0000-0003-3441-5469"]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sarah N Wright","raw_affiliation_strings":["Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA","Program in Bioinformatics and Systems Biology, University of California San Diego, La Jolla, CA, USA"],"raw_orcid":"https://orcid.org/0000-0003-3441-5469","affiliations":[{"raw_affiliation_string":"Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA","institution_ids":["https://openalex.org/I36258959"]},{"raw_affiliation_string":"Program in Bioinformatics and Systems Biology, University of California San Diego, La Jolla, CA, USA","institution_ids":["https://openalex.org/I36258959"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100720988","display_name":"Sung\u2010Joon Park","orcid":"https://orcid.org/0000-0002-1774-9590","observed_orcids":["https://orcid.org/0000-0002-1774-9590"]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"SungJoon Park","raw_affiliation_strings":["Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA","institution_ids":["https://openalex.org/I36258959"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5079868158","display_name":"Ingoo Lee","orcid":"https://orcid.org/0000-0002-8958-2945","observed_orcids":["https://orcid.org/0000-0002-8958-2945"]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"InGoo Lee","raw_affiliation_strings":["Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA","institution_ids":["https://openalex.org/I36258959"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5060670053","display_name":"Laurent Roybon","orcid":"https://orcid.org/0000-0002-5532-4964","observed_orcids":["https://orcid.org/0000-0002-5532-4964"]},"institutions":[{"id":"https://openalex.org/I1317189400","display_name":"Van Andel Institute","ror":"https://ror.org/00wm07d60","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I1317189400"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"laurent roybon","raw_affiliation_strings":["Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA","institution_ids":["https://openalex.org/I1317189400"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5089373684","display_name":"Trey Ideker","orcid":"https://orcid.org/0000-0002-1708-8454","observed_orcids":["https://orcid.org/0000-0002-1708-8454"]},"institutions":[{"id":"https://openalex.org/I36258959","display_name":"University of California San Diego","ror":"https://ror.org/0168r3w48","country_code":"US","type":"education","lineage":["https://openalex.org/I36258959"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Trey Ideker","raw_affiliation_strings":["Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA","Program in Bioinformatics and Systems Biology, University of California San Diego, La Jolla, CA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA","institution_ids":["https://openalex.org/I36258959"]},{"raw_affiliation_string":"Program in Bioinformatics and Systems Biology, University of California San Diego, La Jolla, CA, USA","institution_ids":["https://openalex.org/I36258959"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5089373684"],"corresponding_institution_ids":["https://openalex.org/I36258959"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10085","display_name":"Parkinson's Disease Mechanisms and Treatments","score":0.9984999895095825,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Clinical Neurology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10085","display_name":"Parkinson's Disease Mechanisms and Treatments","score":0.9984999895095825,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Clinical Neurology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T13991","display_name":"Nuclear Receptors and Signaling","score":0.0006000000284984708,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10919","display_name":"Deep Brain Stimulation and Movement Disorders","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Clinical Neurology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/parkinson-s-disease","display_name":"Parkinson's disease","score":0.9990000128746033},{"id":"https://openalex.org/keywords/genetic-risk-variants","display_name":"genetic risk variants","score":0.8550000190734863},{"id":"https://openalex.org/keywords/patient-stratification","display_name":"patient stratification","score":0.6499999761581421},{"id":"https://openalex.org/keywords/dopaminergic-neurons","display_name":"dopaminergic neurons","score":0.9679999947547913},{"id":"https://openalex.org/keywords/oligodendrocyte-precursor-cells","display_name":"oligodendrocyte precursor cells","score":0.9769999980926514},{"id":"https://openalex.org/keywords/excitatory-neurons","display_name":"excitatory neurons","score":0.8740000128746033},{"id":"https://openalex.org/keywords/non-motor-symptoms","display_name":"non-motor symptoms","score":0.843999981880188},{"id":"https://openalex.org/keywords/rem-sleep-behavior-disorder","display_name":"REM sleep behavior disorder","score":0.8790000081062317},{"id":"https://openalex.org/keywords/hyposmia","display_name":"hyposmia","score":0.8399999737739563},{"id":"https://openalex.org/keywords/dementia","display_name":"dementia","score":0.9359999895095825},{"id":"https://openalex.org/keywords/myelin-integrity","display_name":"myelin integrity","score":0.8100000023841858},{"id":"https://openalex.org/keywords/neuregulin-1","display_name":"neuregulin-1","score":0.847000002861023},{"id":"https://openalex.org/keywords/epidermal-growth-factor-like-domain","display_name":"epidermal growth factor-like domain","score":0.9670000076293945},{"id":"https://openalex.org/keywords/oligodendrocyte-development","display_name":"oligodendrocyte development","score":0.906000018119812},{"id":"https://openalex.org/keywords/myelination","display_name":"myelination","score":0.8730000257492065}],"concepts":[{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.7394999861717224},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.6593000292778015},{"id":"https://openalex.org/C189014844","wikidata":"https://www.wikidata.org/wiki/Q189118","display_name":"Cell type","level":3,"score":0.6078000068664551},{"id":"https://openalex.org/C2776985911","wikidata":"https://www.wikidata.org/wiki/Q916698","display_name":"Oligodendrocyte","level":4,"score":0.583299994468689},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.5080999732017517},{"id":"https://openalex.org/C2778609137","wikidata":"https://www.wikidata.org/wiki/Q105790271","display_name":"Myelin","level":3,"score":0.4964999854564667},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.4099999964237213},{"id":"https://openalex.org/C15729860","wikidata":"https://www.wikidata.org/wiki/Q2329919","display_name":"Progenitor","level":4,"score":0.3944999873638153},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.33709999918937683},{"id":"https://openalex.org/C201750760","wikidata":"https://www.wikidata.org/wiki/Q1896218","display_name":"Progenitor cell","level":3,"score":0.3357999920845032},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.33180001378059387},{"id":"https://openalex.org/C3018011982","wikidata":"https://www.wikidata.org/wiki/Q7316120","display_name":"Functional connectivity","level":2,"score":0.3111000061035156},{"id":"https://openalex.org/C150555746","wikidata":"https://www.wikidata.org/wiki/Q210973","display_name":"Cell signaling","level":3,"score":0.30399999022483826},{"id":"https://openalex.org/C2776925932","wikidata":"https://www.wikidata.org/wiki/Q1755122","display_name":"Neurodegeneration","level":3,"score":0.2904999852180481},{"id":"https://openalex.org/C24530287","wikidata":"https://www.wikidata.org/wiki/Q424204","display_name":"Transmembrane protein","level":3,"score":0.2833999991416931},{"id":"https://openalex.org/C148738053","wikidata":"https://www.wikidata.org/wiki/Q210861","display_name":"Cellular differentiation","level":3,"score":0.28139999508857727},{"id":"https://openalex.org/C36503486","wikidata":"https://www.wikidata.org/wiki/Q11235244","display_name":"Domain (mathematical analysis)","level":2,"score":0.27469998598098755},{"id":"https://openalex.org/C2778794669","wikidata":"https://www.wikidata.org/wiki/Q43054","display_name":"Neuron","level":2,"score":0.26339998841285706},{"id":"https://openalex.org/C67339327","wikidata":"https://www.wikidata.org/wiki/Q1502576","display_name":"Gene regulatory network","level":4,"score":0.26010000705718994},{"id":"https://openalex.org/C2780196419","wikidata":"https://www.wikidata.org/wiki/Q1762173","display_name":"Nerve net","level":2,"score":0.2587999999523163},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.2574000060558319},{"id":"https://openalex.org/C2780648746","wikidata":"https://www.wikidata.org/wiki/Q28208871","display_name":"Glutamatergic","level":4,"score":0.25589999556541443},{"id":"https://openalex.org/C2776090121","wikidata":"https://www.wikidata.org/wiki/Q193529","display_name":"T cell","level":3,"score":0.2524000108242035}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1101/2025.09.09.674964","doi":"https://doi.org/10.1101/2025.09.09.674964","is_oa":true,"landing_page_url":"https://doi.org/10.1101/2025.09.09.674964","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.1101/2025.09.09.674964","doi":"https://doi.org/10.1101/2025.09.09.674964","is_oa":true,"landing_page_url":"https://doi.org/10.1101/2025.09.09.674964","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.98580002784729,"display_name":"Good health and well-being"}],"study_designs":[{"id":"https://openalex.org/study-designs/observational-study","display_name":"Observational Study"}],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W3203839345","https://openalex.org/W2952898251","https://openalex.org/W4390717500","https://openalex.org/W4400260194","https://openalex.org/W3080632072","https://openalex.org/W4365504554","https://openalex.org/W4386746243","https://openalex.org/W3091466062","https://openalex.org/W2997890461","https://openalex.org/W4229004479"],"abstract_inverted_index":{"Parkinson's":[0],"disease":[1],"(PD)":[2],"is":[3,116],"classically":[4],"linked":[5],"to":[6,113,142],"dopaminergic":[7],"neuron":[8],"loss,":[9],"but":[10],"emerging":[11],"evidence":[12],"suggests":[13],"broader":[14],"cellular":[15,127],"involvement.":[16],"Here":[17],"we":[18],"show":[19,99],"that":[20,100],"PD":[21,96,130],"risk":[22],"variants":[23],"converge":[24],"on":[25],"distinct":[26],"molecular":[27],"networks":[28],"across":[29],"specific":[30],"brain":[31],"cell":[32],"types,":[33],"enabling":[34],"stratification":[35],"of":[36,129],"patients":[37],"into":[38],"six":[39],"subgroups:":[40],"dopaminergic,":[41],"oligodendrocyte":[42,119],"progenitor":[43],"cells":[44],"(O),":[45],"excitatory":[46],"(E),":[47],"dopaminergic/excitatory,":[48],"dopaminergic/oligodendrocyte":[49],"and":[50,70,110,121,132],"other.":[51],"While":[52],"all":[53],"subgroups":[54],"exhibit":[55,78],"motor":[56],"symptoms,":[57,66],"the":[58,126],"E-group":[59],"individuals":[60,77],"also":[61],"display":[62],"more":[63],"severe":[64],"non-motor":[65,143],"including":[67],"dementia,":[68],"hyposmia,":[69],"REM":[71],"sleep":[72],"behavior":[73],"disorder.":[74],"The":[75],"O-group":[76],"reduced":[79],"myelin":[80],"integrity,":[81],"as":[82,138],"demonstrated":[83],"by":[84],"diffusion":[85],"tensor":[86],"imaging,":[87],"implicating":[88],"NRG6":[89,101],"(formerly":[90],"C1orf56),":[91],"a":[92,103,139],"previously":[93],"uncharacterized":[94],"high-risk":[95],"gene.":[97],"We":[98],"encodes":[102],"conserved":[104],"epidermal":[105],"growth":[106],"factor-like":[107],"domain":[108],"structurally":[109],"functionally":[111],"analogous":[112],"neuregulin-1,":[114],"which":[115],"critical":[117],"for":[118],"development":[120],"myelination.":[122],"These":[123],"findings":[124],"redefine":[125],"architecture":[128],"vulnerability":[131],"identify":[133],"neuregulin-like":[134],"signaling":[135],"in":[136],"oligodendrocytes":[137],"potential":[140],"contributor":[141],"symptoms.":[144]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2025-10-10T00:00:00"}