Exploring environmental modifiers of LRRK2-associated Parkinson’s disease penetrance: An exposomics and metagenomics pilot study on household dust
Pathogenic variants in the Leucine-rich repeat kinase 2 (LRRK2) gene are a primary monogenic cause of Parkinson’s disease (PD). However, the likelihood of developing PD with inherited LRRK2 pathogenic variants differs (a phenomenon known as “reduced penetrance”), with factors including age and geogr...
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Elsevier
2024-12-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412024007372 |
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| author | Begoña Talavera Andújar Sandro L. Pereira Susheel Bhanu Busi Tatiana Usnich Max Borsche Sibel Ertan Peter Bauer Arndt Rolfs Soraya Hezzaz Jenny Ghelfi Norbert Brüggemann Paul Antony Paul Wilmes Christine Klein Anne Grünewald Emma L. Schymanski |
| author_facet | Begoña Talavera Andújar Sandro L. Pereira Susheel Bhanu Busi Tatiana Usnich Max Borsche Sibel Ertan Peter Bauer Arndt Rolfs Soraya Hezzaz Jenny Ghelfi Norbert Brüggemann Paul Antony Paul Wilmes Christine Klein Anne Grünewald Emma L. Schymanski |
| author_sort | Begoña Talavera Andújar |
| collection | DOAJ |
| description | Pathogenic variants in the Leucine-rich repeat kinase 2 (LRRK2) gene are a primary monogenic cause of Parkinson’s disease (PD). However, the likelihood of developing PD with inherited LRRK2 pathogenic variants differs (a phenomenon known as “reduced penetrance”), with factors including age and geographic region, highlighting a potential role for lifestyle and environmental factors in disease onset. To investigate this, household dust samples from four different groups of individuals were analyzed using metabolomics/exposomics and metagenomics approaches: PD+/LRRK2+ (PD patients with pathogenic LRRK2 variants; n = 11), PD-/LRRK2+ (individuals with pathogenic LRRK2 variants but without PD diagnosis; n = 8), iPD (PD of unknown cause; n = 11), and a matched, healthy control group (n = 11). The dust was complemented with metabolomics and lipidomics of matched serum samples, where available. A total of 1,003 chemicals and 163 metagenomic operational taxonomic units (mOTUs) were identified in the dust samples, of which ninety chemicals and ten mOTUs were statistically significant (ANOVA p-value < 0.05). Reduced levels of 2-benzothiazolesulfonic acid (BThSO3) were found in the PD-/LRRK2+ group compared to the PD+/LRRK2+ . Among the significant chemicals tentatively identified in dust, two are hazardous chemical replacements: Bisphenol S (BPS), and perfluorobutane sulfonic acid (PFBuS). Furthermore, various lipids were found altered in serum including different lysophosphatidylethanolamines (LPEs), and lysophosphatidylcholines (LPCs), some with higher levels in the PD+/LRRK2+ group compared to the control group. A cellular study on isogenic neurons generated from a PD+/LRRK2+ patient demonstrated that BPS negatively impacts mitochondrial function, which is implicated in PD pathogenesis. This pilot study demonstrates how non-target metabolomics/exposomics analysis of indoor dust samples complemented with metagenomics can prioritize relevant chemicals that may be potential modifiers of LRRK2 penetrance. |
| format | Article |
| id | doaj-art-53b2fdfaecd24a82a16ac492dfe9127c |
| institution | DOAJ |
| issn | 0160-4120 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj-art-53b2fdfaecd24a82a16ac492dfe9127c2025-08-20T02:52:28ZengElsevierEnvironment International0160-41202024-12-0119410915110.1016/j.envint.2024.109151Exploring environmental modifiers of LRRK2-associated Parkinson’s disease penetrance: An exposomics and metagenomics pilot study on household dustBegoña Talavera Andújar0Sandro L. Pereira1Susheel Bhanu Busi2Tatiana Usnich3Max Borsche4Sibel Ertan5Peter Bauer6Arndt Rolfs7Soraya Hezzaz8Jenny Ghelfi9Norbert Brüggemann10Paul Antony11Paul Wilmes12Christine Klein13Anne Grünewald14Emma L. Schymanski15Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4367 Belvaux, Luxembourg; Corresponding authors.Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4367 Belvaux, LuxembourgLuxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4367 Belvaux, Luxembourg; UK Centre for Ecology and Hydrology, Wallingford, Oxfordshire, United KingdomInstitute of Neurogenetics, University of Lübeck, Lübeck, GermanyInstitute of Neurogenetics, University of Lübeck, Lübeck, Germany; Department of Neurology, University of Lübeck, Lübeck, GermanySchool of Medicine, Department of Neurology, Koc University, Istanbul, TurkeyCENTOGENE GmbH, Rostock, GermanyCENTOGENE GmbH, Rostock, GermanyLuxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4367 Belvaux, LuxembourgLuxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4367 Belvaux, LuxembourgInstitute of Neurogenetics, University of Lübeck, Lübeck, Germany; Department of Neurology, University of Lübeck, Lübeck, GermanyLuxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4367 Belvaux, LuxembourgLuxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4367 Belvaux, Luxembourg; Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, L-4362 Esch-sur-Alzette, LuxembourgInstitute of Neurogenetics, University of Lübeck, Lübeck, GermanyLuxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4367 Belvaux, LuxembourgLuxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4367 Belvaux, Luxembourg; Corresponding authors.Pathogenic variants in the Leucine-rich repeat kinase 2 (LRRK2) gene are a primary monogenic cause of Parkinson’s disease (PD). However, the likelihood of developing PD with inherited LRRK2 pathogenic variants differs (a phenomenon known as “reduced penetrance”), with factors including age and geographic region, highlighting a potential role for lifestyle and environmental factors in disease onset. To investigate this, household dust samples from four different groups of individuals were analyzed using metabolomics/exposomics and metagenomics approaches: PD+/LRRK2+ (PD patients with pathogenic LRRK2 variants; n = 11), PD-/LRRK2+ (individuals with pathogenic LRRK2 variants but without PD diagnosis; n = 8), iPD (PD of unknown cause; n = 11), and a matched, healthy control group (n = 11). The dust was complemented with metabolomics and lipidomics of matched serum samples, where available. A total of 1,003 chemicals and 163 metagenomic operational taxonomic units (mOTUs) were identified in the dust samples, of which ninety chemicals and ten mOTUs were statistically significant (ANOVA p-value < 0.05). Reduced levels of 2-benzothiazolesulfonic acid (BThSO3) were found in the PD-/LRRK2+ group compared to the PD+/LRRK2+ . Among the significant chemicals tentatively identified in dust, two are hazardous chemical replacements: Bisphenol S (BPS), and perfluorobutane sulfonic acid (PFBuS). Furthermore, various lipids were found altered in serum including different lysophosphatidylethanolamines (LPEs), and lysophosphatidylcholines (LPCs), some with higher levels in the PD+/LRRK2+ group compared to the control group. A cellular study on isogenic neurons generated from a PD+/LRRK2+ patient demonstrated that BPS negatively impacts mitochondrial function, which is implicated in PD pathogenesis. This pilot study demonstrates how non-target metabolomics/exposomics analysis of indoor dust samples complemented with metagenomics can prioritize relevant chemicals that may be potential modifiers of LRRK2 penetrance.http://www.sciencedirect.com/science/article/pii/S0160412024007372Indoor environmentExposomicsMetagenomicsParkinson’s diseaseLeucine-rich repeat kinase 2 (LRRK2)Bisphenol S |
| spellingShingle | Begoña Talavera Andújar Sandro L. Pereira Susheel Bhanu Busi Tatiana Usnich Max Borsche Sibel Ertan Peter Bauer Arndt Rolfs Soraya Hezzaz Jenny Ghelfi Norbert Brüggemann Paul Antony Paul Wilmes Christine Klein Anne Grünewald Emma L. Schymanski Exploring environmental modifiers of LRRK2-associated Parkinson’s disease penetrance: An exposomics and metagenomics pilot study on household dust Environment International Indoor environment Exposomics Metagenomics Parkinson’s disease Leucine-rich repeat kinase 2 (LRRK2) Bisphenol S |
| title | Exploring environmental modifiers of LRRK2-associated Parkinson’s disease penetrance: An exposomics and metagenomics pilot study on household dust |
| title_full | Exploring environmental modifiers of LRRK2-associated Parkinson’s disease penetrance: An exposomics and metagenomics pilot study on household dust |
| title_fullStr | Exploring environmental modifiers of LRRK2-associated Parkinson’s disease penetrance: An exposomics and metagenomics pilot study on household dust |
| title_full_unstemmed | Exploring environmental modifiers of LRRK2-associated Parkinson’s disease penetrance: An exposomics and metagenomics pilot study on household dust |
| title_short | Exploring environmental modifiers of LRRK2-associated Parkinson’s disease penetrance: An exposomics and metagenomics pilot study on household dust |
| title_sort | exploring environmental modifiers of lrrk2 associated parkinson s disease penetrance an exposomics and metagenomics pilot study on household dust |
| topic | Indoor environment Exposomics Metagenomics Parkinson’s disease Leucine-rich repeat kinase 2 (LRRK2) Bisphenol S |
| url | http://www.sciencedirect.com/science/article/pii/S0160412024007372 |
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