{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Le Guen Y"],"funding":["European Research Council","NIA NIH HHS","Medical Research Council","NINDS NIH HHS"],"pagination":["e2302720120"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10483635"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["120(36)"],"pubmed_abstract":["Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of <i>HLA-DRB1</i>*04 subtypes best accounted for the association, strongest with <i>HLA-DRB1</i>*04:04 and <i>HLA-DRB1</i>*04:07, and intermediary with <i>HLA-DRB1</i>*04:01 and <i>HLA-DRB1</i>*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective <i>HLA-DRB1</i>*04 subtypes strongly"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by &lt;i&gt;HLA-DRB1*04&lt;/i&gt; subtypes."],"pmcid":["PMC10483635"],"funding_grant_id":["U24 AG021886","MR/T04604X/1","R01 AG060747","681712","UKDRI-3003","R01 NS112499","MR/L010305/1","P30 AG066515","R01 AG066206","UKDRI-Car001"],"pubmed_authors":["Rossi G","EADI","Asian Parkinson’s Disease Genetics consortium","Darling D","de Mendonca A","Scheltens P","Zhang J","Williams J","van der Flier W","Gim J","Kucukali F","Pinol-Ripoll G","Caffarra P","Scherbaum N","Niida S","Borroni B","Popp J","Squassina A","Seripa D","Talyansky SD","Kern S","Waern M","Toda T","Moebus S","He Z","Porcel LM","Clarimon J","Van Duin C","EADB","Jung YJ","Foo JN","Grunblatt E","Lin L","Thomassen JQ","Moreno F","Tan EK","Bullido MJ","Nacmias B","Yu E","Sanchez-Juan P","Boland A","Naito T","Pasquier F","Benussi L","Sims R","Satake W","Schneider A","Teunissen C","Ramirez A","GERAD","Dufouil C","Jansen I","Zettergren A","Garcia-Gonzalez P","Ikeuchi T","Papma J","de Rojas I","Lambert JC","Belloy ME","Graff C","Verhey F","Vyhnalek M","Yogeshwar SM","Ruiz A","Ozaki K","Daniele A","Lee KH","Galimberti D","DemGene","Pijnenburg YAL","Real LM","Kehoe PG","Scarmeas N","Mir P","Ramakers I","Zetterberg H","Amouyel P","Royo LJ","Giedraitis V","Nordestgaard BG","Andreassen OA","Holstege H","Ambati A","Bellenguez C","Peters O","Puerta R","Arosio B","Le Guen Y","Park H","DEGESCO consortium","Jessen F","Wiltfang J","Solfrizzi V","Tremolizzo L","Dichgans M","Garcia-Ribas G","Debette S","Peixoto Leal T","Deleuze JF","Damotte V","Hausner L","Heilmann-Heimbach S","Boada M","Hiltunen M","Papenberg G","Garcia-Alberca JM","Greicius MD","Hort J","Blennow K","Duzel E","Spalletta G","Sleegers K","Mignot E","Goldhardt O","Mehrabian S","Riedel-Heller S","Miyashita A","During E","Tegos T","Hanon O","Frikke-Schmidt R","Parveen K","Morizono T","Mecocci P","Nicolas G","Parnetti L","Perez-Tur J","Alvarez V","Jurgen D","Ingelsson M","Nicolas A","Masullo C","Ross OA","Luo G","Sempere V","Grenier-Boley B","Pastor P","Rujescu D","Kuulasmaa T","Rodriguez-Rodriguez E","Rainero I","Gan-Or Z","Skoog I","Tsolaki M","Okada Y","van Swieten J","Mata I","Lian MM","Sanchez-Valle R","GR@ACE study group"],"additional_accession":[]},"is_claimable":false,"name":"Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by &lt;i&gt;HLA-DRB1*04&lt;/i&gt; subtypes.","description":"Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of <i>HLA-DRB1</i>*04 subtypes best accounted for the association, strongest with <i>HLA-DRB1</i>*04:04 and <i>HLA-DRB1</i>*04:07, and intermediary with <i>HLA-DRB1</i>*04:01 and <i>HLA-DRB1</i>*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective <i>HLA-DRB1</i>*04 subtypes strongly","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Sep","modification":"2026-05-28T13:15:12.954Z","creation":"2024-10-17T15:55:08.822Z"},"accession":"S-EPMC10483635","cross_references":{"pubmed":["37643212"],"doi":["10.1073/pnas.2302720120"]}}