{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:32:25Z","timestamp":1768563145219,"version":"3.49.0"},"posted":{"date-parts":[[2023,8,30]]},"group-title":"Neurology","reference-count":62,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,9,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    Levodopa-induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson\u2019s disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including\n                    <jats:italic>GBA1<\/jats:italic>\n                    and\n                    <jats:italic>LRRK2<\/jats:italic>\n                    .\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To investigate the effects of genetic variants on risk and time to LID.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We performed a genome-wide association study (GWAS) and analyses focused on\n                    <jats:italic>GBA1<\/jats:italic>\n                    and\n                    <jats:italic>LRRK2<\/jats:italic>\n                    variants. We also calculated polygenic risk scores including risk variants for PD and variants in genes involved in the dopaminergic transmission pathway. To test the influence of genetics on LID risk we used logistic regression, and to examine its impact on time to LID we performed Cox regression including 1,612 PD patients with and 3,175 without LID.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    We found that\n                    <jats:italic>GBA1<\/jats:italic>\n                    variants were associated with LID risk (OR=1.65, 95% CI=1.21-2.26, p=0.0017) and\n                    <jats:italic>LRRK2<\/jats:italic>\n                    variants with reduced time to LID onset (HR=1.42, 95% CI=1.09-1.84, p=0.0098). The fourth quartile of the PD PRS was associated with increased LID risk (OR\n                    <jats:sub>fourth_quartile<\/jats:sub>\n                    =1.27, 95% CI=1.03-1.56,\n                    <jats:italic>p=<\/jats:italic>\n                    0.0210). The third and fourth dopamine pathway PRS quartiles were associated with a reduced time to development of LID (HR\n                    <jats:sub>third_quartile=<\/jats:sub>\n                    1.38, 95% CI=1.07-1.79,\n                    <jats:italic>p=<\/jats:italic>\n                    0.0128; HR\n                    <jats:sub>fourth_quartile=<\/jats:sub>\n                    1.38, 95% CI=1.06-1.78,\n                    <jats:italic>p=<\/jats:italic>\n                    0.0147).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study suggests that variants implicated in PD and in the dopaminergic transmission pathway play a role in the risk\/time to develop LID. Further studies will be necessary to examine how these findings can inform clinical care.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.08.28.23294610","type":"posted-content","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T15:40:13Z","timestamp":1693410013000},"source":"Crossref","is-referenced-by-count":0,"title":["Dopamine pathway and Parkinson\u2019s risk variants are associated with levodopa-induced dyskinesia"],"prefix":"10.64898","author":[{"given":"Yuri L.","family":"Sosero","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Bandres-Ciga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart","family":"Ferwerda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria T. P.","family":"Tocino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00ecaz R.","family":"Belloso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pilar","family":"G\u00f3mez-Garre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johann","family":"Faouzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pille","family":"Taba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas","family":"Pavelka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tain\u00e0 M.","family":"Marques","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarissa P. 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