Shared genetic etiology between Parkinson’s disease and blood levels of specific lipids

Abstract Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies. The mechanisms underlying these molecular and cellular effects are largely unknown. Previously, based on genetic and other data, we built a molecul...

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Autores principales:	Helena Xicoy, Cornelius JHM Klemann, Ward De Witte, Marijn B Martens, Gerard JM Martens, Geert Poelmans
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/e240c660e8524bc1a0cfe4a057c8995d
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spelling	oai:doaj.org-article:e240c660e8524bc1a0cfe4a057c8995d2021-12-02T13:34:53ZShared genetic etiology between Parkinson’s disease and blood levels of specific lipids10.1038/s41531-021-00168-92373-8057https://doaj.org/article/e240c660e8524bc1a0cfe4a057c8995d2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41531-021-00168-9https://doaj.org/toc/2373-8057Abstract Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies. The mechanisms underlying these molecular and cellular effects are largely unknown. Previously, based on genetic and other data, we built a molecular landscape of PD that highlighted a central role for lipids. To explore which lipid species may be involved in PD pathology, we used published genome-wide association study (GWAS) data to conduct polygenic risk score-based analyses to examine putative genetic sharing between PD and blood levels of 370 lipid species and lipid-related molecules. We found a shared genetic etiology between PD and blood levels of 25 lipids. We then used data from a much-extended GWAS of PD to try and corroborate our findings. Across both analyses, we found genetic overlap between PD and blood levels of eight lipid species, namely two polyunsaturated fatty acids (PUFA 20:3n3-n6 and 20:4n6), four triacylglycerols (TAG 44:1, 46:1, 46:2, and 48:0), phosphatidylcholine aa 32:3 (PC aa 32:3) and sphingomyelin 26:0 (SM 26:0). Analysis of the concordance—the agreement in genetic variant effect directions across two traits—revealed a significant negative concordance between PD and blood levels of the four triacylglycerols and PC aa 32:3 and a positive concordance between PD and blood levels of both PUFA and SM 26:0. Taken together, our analyses imply that genetic variants associated with PD modulate blood levels of a specific set of lipid species supporting a key role of these lipids in PD etiology.Helena XicoyCornelius JHM KlemannWard De WitteMarijn B MartensGerard JM MartensGeert PoelmansNature PortfolioarticleNeurology. Diseases of the nervous systemRC346-429ENnpj Parkinson's Disease, Vol 7, Iss 1, Pp 1-8 (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 Helena Xicoy Cornelius JHM Klemann Ward De Witte Marijn B Martens Gerard JM Martens Geert Poelmans Shared genetic etiology between Parkinson’s disease and blood levels of specific lipids
description	Abstract Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies. The mechanisms underlying these molecular and cellular effects are largely unknown. Previously, based on genetic and other data, we built a molecular landscape of PD that highlighted a central role for lipids. To explore which lipid species may be involved in PD pathology, we used published genome-wide association study (GWAS) data to conduct polygenic risk score-based analyses to examine putative genetic sharing between PD and blood levels of 370 lipid species and lipid-related molecules. We found a shared genetic etiology between PD and blood levels of 25 lipids. We then used data from a much-extended GWAS of PD to try and corroborate our findings. Across both analyses, we found genetic overlap between PD and blood levels of eight lipid species, namely two polyunsaturated fatty acids (PUFA 20:3n3-n6 and 20:4n6), four triacylglycerols (TAG 44:1, 46:1, 46:2, and 48:0), phosphatidylcholine aa 32:3 (PC aa 32:3) and sphingomyelin 26:0 (SM 26:0). Analysis of the concordance—the agreement in genetic variant effect directions across two traits—revealed a significant negative concordance between PD and blood levels of the four triacylglycerols and PC aa 32:3 and a positive concordance between PD and blood levels of both PUFA and SM 26:0. Taken together, our analyses imply that genetic variants associated with PD modulate blood levels of a specific set of lipid species supporting a key role of these lipids in PD etiology.
format	article
author	Helena Xicoy Cornelius JHM Klemann Ward De Witte Marijn B Martens Gerard JM Martens Geert Poelmans
author_facet	Helena Xicoy Cornelius JHM Klemann Ward De Witte Marijn B Martens Gerard JM Martens Geert Poelmans
author_sort	Helena Xicoy
title	Shared genetic etiology between Parkinson’s disease and blood levels of specific lipids
title_short	Shared genetic etiology between Parkinson’s disease and blood levels of specific lipids
title_full	Shared genetic etiology between Parkinson’s disease and blood levels of specific lipids
title_fullStr	Shared genetic etiology between Parkinson’s disease and blood levels of specific lipids
title_full_unstemmed	Shared genetic etiology between Parkinson’s disease and blood levels of specific lipids
title_sort	shared genetic etiology between parkinson’s disease and blood levels of specific lipids
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e240c660e8524bc1a0cfe4a057c8995d
work_keys_str_mv	AT helenaxicoy sharedgeneticetiologybetweenparkinsonsdiseaseandbloodlevelsofspecificlipids AT corneliusjhmklemann sharedgeneticetiologybetweenparkinsonsdiseaseandbloodlevelsofspecificlipids AT warddewitte sharedgeneticetiologybetweenparkinsonsdiseaseandbloodlevelsofspecificlipids AT marijnbmartens sharedgeneticetiologybetweenparkinsonsdiseaseandbloodlevelsofspecificlipids AT gerardjmmartens sharedgeneticetiologybetweenparkinsonsdiseaseandbloodlevelsofspecificlipids AT geertpoelmans sharedgeneticetiologybetweenparkinsonsdiseaseandbloodlevelsofspecificlipids
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Shared genetic etiology between Parkinson’s disease and blood levels of specific lipids

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