{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:07:33Z","timestamp":1768565253052,"version":"3.49.0"},"posted":{"date-parts":[[2023,8,25]]},"group-title":"Genetic and Genomic Medicine","reference-count":50,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To investigate the association between a Parkinson\u2019s disease (PD)-specific polygenic score (PGS) and protective lifestyle factors on age at onset (AAO) in PD.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We included data from 4375 patients with idiopathic PD, 167 patients with\n                    <jats:italic>GBA1<\/jats:italic>\n                    -PD, and 3091 healthy controls of European ancestry from AMP-PD, PPMI, and Fox Insight cohorts. The PGS was calculated based on a previously proposed composition of 1805 variants. The association between PGS and lifestyle factors (i.e., coffee, tobacco, and aspirin) on AAO was assessed with linear and Cox proportional hazards models.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    The PGS showed a negative association with AAO (\u03b2=-1.07, p=6x10\n                    <jats:sup>-7<\/jats:sup>\n                    ). The use of one, two, or three of the protective lifestyle factors showed a reduction in the hazard ratio by 21% (p=0.0001), 45% (p&lt;2x10\n                    <jats:sup>-16<\/jats:sup>\n                    ), and 55% (p&lt;2x10\n                    <jats:sup>-16<\/jats:sup>\n                    ), respectively, compared to no use. An additive effect of aspirin (\u03b2=7.61, p=8x10\n                    <jats:sup>-7<\/jats:sup>\n                    ) and PGS (\u03b2=-1.63, p=0.0112) was found for AAO without an interaction (p=0.9789) in the linear regressions, and similar effects were seen for tobacco. Aspirin is shown to be a better predictor of AAO (R\n                    <jats:sup>2<\/jats:sup>\n                    =0.1740) compared to coffee and tobacco use (R\n                    <jats:sup>2<\/jats:sup>\n                    =0.0243, R\n                    <jats:sup>2<\/jats:sup>\n                    =0.0295) or the PGS (R\n                    <jats:sup>2<\/jats:sup>\n                    =0.0141). In contrast, no association between aspirin and AAO was found in\n                    <jats:italic>GBA1<\/jats:italic>\n                    -PD (p&gt;0.05).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>In our cohort, coffee, tobacco, aspirin, and PGS are independent predictors of PD AAO. Additionally, lifestyle factors seem to have a greater influence on AAO than common genetic risk variants with aspirin presenting the largest effect. External validation of our findings is needed.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.08.25.23294466","type":"posted-content","created":{"date-parts":[[2023,8,26]],"date-time":"2023-08-26T00:30:16Z","timestamp":1693009816000},"source":"Crossref","is-referenced-by-count":2,"title":["The combined effect of lifestyle factors and polygenic scores on age at onset in Parkinson\u2019s disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2308-9330","authenticated-orcid":false,"given":"Carolin","family":"Gabbert","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonie","family":"Bl\u00f6baum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa","family":"L\u00fcth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inke R.","family":"K\u00f6nig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amke","family":"Caliebe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Koch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bj\u00f6rn-Hergen","family":"Laabs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Klein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne","family":"Trinh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023083009550744000_2023.08.25.23294466v1.1","doi-asserted-by":"crossref","unstructured":"Jia F , Fellner A , Kumar KR . 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