Fine mapping of the HLA locus in Parkinson’s disease in Europeans

Abstract We fine mapped the leukocyte antigen (HLA) region in 13,770 Parkinson’s disease (PD) patients, 20,214 proxy-cases, and 490,861 controls of European origin. Four HLA types were associated with PD after correction for multiple comparisons, HLA-DQA1*03:01, HLA-DQB1*03:02, HLA-DRB1*04:01, and H...

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Autores principales:	Eric Yu, Aditya Ambati, Maren Stolp Andersen, Lynne Krohn, Mehrdad A. Estiar, Prabhjyot Saini, Konstantin Senkevich, Yuri L. Sosero, Ashwin Ashok Kumar Sreelatha, Jennifer A. Ruskey, Farnaz Asayesh, Dan Spiegelman, Mathias Toft, Marte K. Viken, Manu Sharma, Cornelis Blauwendraat, Lasse Pihlstrøm, Emmanuel Mignot, Ziv Gan-Or
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/f4f24fcd8c2b4d28bc704742820e3662
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spelling	oai:doaj.org-article:f4f24fcd8c2b4d28bc704742820e36622021-12-02T15:14:37ZFine mapping of the HLA locus in Parkinson’s disease in Europeans10.1038/s41531-021-00231-52373-8057https://doaj.org/article/f4f24fcd8c2b4d28bc704742820e36622021-09-01T00:00:00Zhttps://doi.org/10.1038/s41531-021-00231-5https://doaj.org/toc/2373-8057Abstract We fine mapped the leukocyte antigen (HLA) region in 13,770 Parkinson’s disease (PD) patients, 20,214 proxy-cases, and 490,861 controls of European origin. Four HLA types were associated with PD after correction for multiple comparisons, HLA-DQA103:01, HLA-DQB103:02, HLA-DRB104:01, and HLA-DRB104:04. Haplotype analyses followed by amino acid analysis and conditional analyses suggested that the association is protective and primarily driven by three specific amino acid polymorphisms present in most HLA-DRB1*04 subtypes—11V, 13H, and 33H (OR = 0.87, 95% CI: 0.83–0.90, p < 8.23 × 10−9 for all three variants). No other effects were present after adjustment for these amino acids. Our results suggest that specific HLA-DRB1 variants are associated with reduced risk of PD, providing additional evidence for the role of the immune system in PD. Although effect size is small and has no diagnostic significance, understanding the mechanism underlying this association may lead to the identification of new targets for therapeutics development.Eric YuAditya AmbatiMaren Stolp AndersenLynne KrohnMehrdad A. EstiarPrabhjyot SainiKonstantin SenkevichYuri L. SoseroAshwin Ashok Kumar SreelathaJennifer A. RuskeyFarnaz AsayeshDan SpiegelmanMathias ToftMarte K. VikenManu SharmaCornelis BlauwendraatLasse PihlstrømEmmanuel MignotZiv Gan-OrNature PortfolioarticleNeurology. Diseases of the nervous systemRC346-429ENnpj Parkinson's Disease, Vol 7, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurology. Diseases of the nervous system RC346-429 Eric Yu Aditya Ambati Maren Stolp Andersen Lynne Krohn Mehrdad A. Estiar Prabhjyot Saini Konstantin Senkevich Yuri L. Sosero Ashwin Ashok Kumar Sreelatha Jennifer A. Ruskey Farnaz Asayesh Dan Spiegelman Mathias Toft Marte K. Viken Manu Sharma Cornelis Blauwendraat Lasse Pihlstrøm Emmanuel Mignot Ziv Gan-Or Fine mapping of the HLA locus in Parkinson’s disease in Europeans
description	Abstract We fine mapped the leukocyte antigen (HLA) region in 13,770 Parkinson’s disease (PD) patients, 20,214 proxy-cases, and 490,861 controls of European origin. Four HLA types were associated with PD after correction for multiple comparisons, HLA-DQA103:01, HLA-DQB103:02, HLA-DRB104:01, and HLA-DRB104:04. Haplotype analyses followed by amino acid analysis and conditional analyses suggested that the association is protective and primarily driven by three specific amino acid polymorphisms present in most HLA-DRB1*04 subtypes—11V, 13H, and 33H (OR = 0.87, 95% CI: 0.83–0.90, p < 8.23 × 10−9 for all three variants). No other effects were present after adjustment for these amino acids. Our results suggest that specific HLA-DRB1 variants are associated with reduced risk of PD, providing additional evidence for the role of the immune system in PD. Although effect size is small and has no diagnostic significance, understanding the mechanism underlying this association may lead to the identification of new targets for therapeutics development.
format	article
author	Eric Yu Aditya Ambati Maren Stolp Andersen Lynne Krohn Mehrdad A. Estiar Prabhjyot Saini Konstantin Senkevich Yuri L. Sosero Ashwin Ashok Kumar Sreelatha Jennifer A. Ruskey Farnaz Asayesh Dan Spiegelman Mathias Toft Marte K. Viken Manu Sharma Cornelis Blauwendraat Lasse Pihlstrøm Emmanuel Mignot Ziv Gan-Or
author_facet	Eric Yu Aditya Ambati Maren Stolp Andersen Lynne Krohn Mehrdad A. Estiar Prabhjyot Saini Konstantin Senkevich Yuri L. Sosero Ashwin Ashok Kumar Sreelatha Jennifer A. Ruskey Farnaz Asayesh Dan Spiegelman Mathias Toft Marte K. Viken Manu Sharma Cornelis Blauwendraat Lasse Pihlstrøm Emmanuel Mignot Ziv Gan-Or
author_sort	Eric Yu
title	Fine mapping of the HLA locus in Parkinson’s disease in Europeans
title_short	Fine mapping of the HLA locus in Parkinson’s disease in Europeans
title_full	Fine mapping of the HLA locus in Parkinson’s disease in Europeans
title_fullStr	Fine mapping of the HLA locus in Parkinson’s disease in Europeans
title_full_unstemmed	Fine mapping of the HLA locus in Parkinson’s disease in Europeans
title_sort	fine mapping of the hla locus in parkinson’s disease in europeans
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f4f24fcd8c2b4d28bc704742820e3662
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Fine mapping of the HLA locus in Parkinson’s disease in Europeans

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