Lasse Pihlstrøm1,2, Kristina Rebekka Morset1, Espen Grimstad1, Valeria Vitelli3, Mathias Toft2. 1. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. 2. Department of Neurology, Oslo University Hospital, Oslo, Norway. 3. Oslo Center for Biostatistics and Epidemiology, Department of Biostatistics, University of Oslo, Oslo, Norway.
Abstract
BACKGROUND: The contribution of genetic variability to clinical heterogeneity in Parkinson's disease is insufficiently understood. We aimed to investigate the effect of cumulative genetic risk on clinical outcomes. METHODS: In a single-center study of 336 patients we genotyped 19 independent susceptibility variants identified in genome-wide association studies of Parkinson's disease. We tested for association between a cumulative genetic risk score and 3 outcome measures: survival, time until progression to Hoehn and Yahr stage 3, and Unified Parkinson's Disease Rating Scale motor score severity. RESULTS: Genetic risk score was significantly associated with time from diagnosis to Hoehn and Yahr stage 3 in a Cox regression model (P = 0.010). We observed no clear association for the other outcomes. CONCLUSIONS: We present results linking cumulative genetic risk to a motor outcome in Parkinson's disease. Our findings provide a valuable starting point for future large-scale efforts to map the genetic determinants of phenotypic variability.
BACKGROUND: The contribution of genetic variability to clinical heterogeneity in Parkinson's disease is insufficiently understood. We aimed to investigate the effect of cumulative genetic risk on clinical outcomes. METHODS: In a single-center study of 336 patients we genotyped 19 independent susceptibility variants identified in genome-wide association studies of Parkinson's disease. We tested for association between a cumulative genetic risk score and 3 outcome measures: survival, time until progression to Hoehn and Yahr stage 3, and Unified Parkinson's Disease Rating Scale motor score severity. RESULTS: Genetic risk score was significantly associated with time from diagnosis to Hoehn and Yahr stage 3 in a Cox regression model (P = 0.010). We observed no clear association for the other outcomes. CONCLUSIONS: We present results linking cumulative genetic risk to a motor outcome in Parkinson's disease. Our findings provide a valuable starting point for future large-scale efforts to map the genetic determinants of phenotypic variability.
Authors: Lasse Pihlstrøm; Cornelis Blauwendraat; Chiara Cappelletti; Victoria Berge-Seidl; Margrete Langmyhr; Sandra Pilar Henriksen; Wilma D J van de Berg; J Raphael Gibbs; Mark R Cookson; Andrew B Singleton; Mike A Nalls; Mathias Toft Journal: Ann Neurol Date: 2018-08-26 Impact factor: 10.422
Authors: Victoria Berge-Seidl; Lasse Pihlstrøm; Zbigniew K Wszolek; Owen A Ross; Mathias Toft Journal: Neurobiol Aging Date: 2018-09-22 Impact factor: 4.673
Authors: Triin Laisk-Podar; Cecilia M Lindgren; Maire Peters; Juha S Tapanainen; Cornelis B Lambalk; Andres Salumets; Reedik Mägi Journal: Trends Endocrinol Metab Date: 2016-05-21 Impact factor: 12.015
Authors: Young-Gun Lee; Seun Jeon; Sung Woo Kang; Mincheol Park; Kyoungwon Baik; Han Soo Yoo; Seok Jong Chung; Seong Ho Jeong; Jin Ho Jung; Phil Hyu Lee; Young Ho Sohn; Alan C Evans; Byoung Seok Ye Journal: Alzheimers Dement (Amst) Date: 2021-05-21