{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:11:17Z","timestamp":1790705477447,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T00:00:00Z","timestamp":1689897600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR2488"],"award-info":[{"award-number":["FOR2488"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","award":["MJFF\u2010021227 & MJFF\u2010019271"],"award-info":[{"award-number":["MJFF\u2010021227 & MJFF\u2010019271"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>A mitochondrial polygenic score (MGS) is composed of genes related to mitochondrial function and found to be associated with Parkinson's disease (PD) risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the impact of the MGS and lifestyle\/environment on age at onset (AAO) in LRRK2 p.Gly2019Ser parkinsonism (<jats:italic>LRRK2<\/jats:italic>\u2010PD) and idiopathic PD (iPD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included N\u2009=\u2009486 patients with <jats:italic>LRRK2<\/jats:italic>\u2010PD and N\u2009=\u20099259 with iPD from the Accelerating Medicines Partnership\u00ae Parkinson's Disease Knowledge Platform (AMP\u2010PD), Fox Insight, and a Tunisian Arab\u2010Berber founder population. Genotyping data were used to perform the MGS analysis. Additionally, lifestyle\/environmental data were obtained from the PD Risk Factor Questionnaire (PD\u2010RFQ). Linear regression models were used to assess the relationship between MGS, lifestyle\/environment, and AAO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our derived MGS was significantly higher in PD cases compared with controls (<jats:italic>P<\/jats:italic>\u2009=\u20091.1\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>). We observed that higher MGS was significantly associated with earlier AAO in <jats:italic>LRRK2<\/jats:italic>\u2010PD (<jats:italic>P<\/jats:italic>\u2009=\u20090.047, <jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u22121.40) and there was the same trend with a smaller effect size in iPD (<jats:italic>P<\/jats:italic>\u2009=\u20090.231, <jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.22). There was a correlation between MGS and AAO in <jats:italic>LRRK2<\/jats:italic>\u2010PD patients of European descent (<jats:italic>P<\/jats:italic>\u2009=\u20090.049, <jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.12) that was visibly less pronounced in Tunisians (<jats:italic>P<\/jats:italic>\u2009=\u20090.449, <jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.05). We found that the MGS interacted with caffeinated soda consumption (<jats:italic>P<\/jats:italic>\u2009=\u20090.003, <jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u22125.65) in <jats:italic>LRRK2<\/jats:italic>\u2010PD and with tobacco use (<jats:italic>P<\/jats:italic>\u2009=\u20090.010, <jats:italic>\u03b2<\/jats:italic>\u2009=\u20091.32) in iPD. Thus, patients with a high MGS had an earlier AAO only if they consumed caffeinated soda or were non\u2010smokers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The MGS was more strongly associated with earlier AAO in <jats:italic>LRRK2<\/jats:italic>\u2010PD compared with iPD. Caffeinated soda consumption or tobacco use interacted with MGS to predict AAO. Our study suggests gene\u2013environment interactions as modifiers of AAO in <jats:italic>LRRK2<\/jats:italic>\u2010PD. \u00a9 2023 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29563","type":"journal-article","created":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T02:07:00Z","timestamp":1689991620000},"page":"1837-1849","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Interaction of Mitochondrial Polygenic Score and Lifestyle Factors in <scp>LRRK2<\/scp> p.<scp>Gly2019Ser<\/scp> Parkinsonism"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0458-0498","authenticated-orcid":false,"given":"Theresa","family":"L\u00fcth","sequence":"first","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2308-9330","authenticated-orcid":false,"given":"Carolin","family":"Gabbert","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Koch","sequence":"additional","affiliation":[{"name":"Institute of Medical Informatics and Statistics Kiel University, University Hospital Schleswig\u2010Holstein  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inke R.","family":"K\u00f6nig","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry and Statistics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amke","family":"Caliebe","sequence":"additional","affiliation":[{"name":"Institute of Medical Informatics and Statistics Kiel University, University Hospital Schleswig\u2010Holstein  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn\u2010Hergen","family":"Laabs","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry and Statistics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faycel","family":"Hentati","sequence":"additional","affiliation":[{"name":"Neurology Department National Institute of Neurology  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia Ben","family":"Sassi","sequence":"additional","affiliation":[{"name":"Neurology Department National Institute of Neurology  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rim","family":"Amouri","sequence":"additional","affiliation":[{"name":"Neurology Department National Institute of Neurology  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Spielmann","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Klein","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Gr\u00fcnewald","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Luxembourg Centre for Systems Biomedicine University of Luxembourg  Esch\u2010sur\u2010Alzette Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Farrer","sequence":"additional","affiliation":[{"name":"Clinical Genomics University of Florida  Gainesville FL 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