BACKGROUND: Little is known regarding genetic factors associated with motor or cognitive outcomes in Parkinson's disease (PD). OBJECTIVE: To identify common genetic variants associated with motor and cognitive outcomes in PD. METHODS: The sample consisted of 443 PD cases included in the first genome-wide association study (GWAS) of PD. Methods included telephone interview assessments of motor and cognitive outcomes, a median 9 years following the initial clinical assessments. Analyses included Cox proportional hazard models to study the association of 198,345 single nucleotide polymorphisms (SNPs) with survival free of Hoehn and Yahr stage ≥ 4 (motor outcome), and either TICS-M ≤ 27 or AD-8 ≥ 2 (cognitive outcomes). RESULTS: The SNP rs10958605 in the C8orf4 gene had the smallest p value in analyses of the motor outcome (HR = 1.81; 95% CI = 1.42-2.31; p = 1.51 × 10(-6)). The SNP rs6482992 in the CLRN3 gene had the smallest p value in analyses of the cognitive outcome (HR = 2.03, 95% CI 1.47-2.79, p = 4.08 × 10(-6)). However, no SNP associations were significant after Bonferroni correction. The C8orf4 gene had small p values for both motor and cognitive outcomes, highlighting inflammation as a possible pathogenesis mechanism for progression in PD. CONCLUSIONS: This study suggests that common variants in several genes may be associated with motor and cognitive outcomes in PD, with biological plausibility.
BACKGROUND: Little is known regarding genetic factors associated with motor or cognitive outcomes in Parkinson's disease (PD). OBJECTIVE: To identify common genetic variants associated with motor and cognitive outcomes in PD. METHODS: The sample consisted of 443 PD cases included in the first genome-wide association study (GWAS) of PD. Methods included telephone interview assessments of motor and cognitive outcomes, a median 9 years following the initial clinical assessments. Analyses included Cox proportional hazard models to study the association of 198,345 single nucleotide polymorphisms (SNPs) with survival free of Hoehn and Yahr stage ≥ 4 (motor outcome), and either TICS-M ≤ 27 or AD-8 ≥ 2 (cognitive outcomes). RESULTS: The SNP rs10958605 in the C8orf4 gene had the smallest p value in analyses of the motor outcome (HR = 1.81; 95% CI = 1.42-2.31; p = 1.51 × 10(-6)). The SNP rs6482992 in the CLRN3 gene had the smallest p value in analyses of the cognitive outcome (HR = 2.03, 95% CI 1.47-2.79, p = 4.08 × 10(-6)). However, no SNP associations were significant after Bonferroni correction. The C8orf4 gene had small p values for both motor and cognitive outcomes, highlighting inflammation as a possible pathogenesis mechanism for progression in PD. CONCLUSIONS: This study suggests that common variants in several genes may be associated with motor and cognitive outcomes in PD, with biological plausibility.
Authors: J E Galvin; C M Roe; K K Powlishta; M A Coats; S J Muich; E Grant; J P Miller; M Storandt; J C Morris Journal: Neurology Date: 2005-08-23 Impact factor: 9.910
Authors: David A Hinds; Laura L Stuve; Geoffrey B Nilsen; Eran Halperin; Eleazar Eskin; Dennis G Ballinger; Kelly A Frazer; David R Cox Journal: Science Date: 2005-02-18 Impact factor: 47.728
Authors: Walter A Rocca; Brett J Peterson; Shannon K McDonnell; James H Bower; J Eric Ahlskog; Daniel J Schaid; Demetrius M Maraganore Journal: Neuroepidemiology Date: 2005-01-25 Impact factor: 3.282
Authors: Alexis Elbaz; James H Bower; Brett J Peterson; Demetrius M Maraganore; Shannon K McDonnell; J Eric Ahlskog; Daniel J Schaid; Walter A Rocca Journal: Arch Neurol Date: 2003-01
Authors: Katerina Markopoulou; Joanna M Biernacka; Sebastian M Armasu; Kari J Anderson; J Eric Ahlskog; Bruce A Chase; Sun Ju Chung; Julie M Cunningham; Matthew Farrer; Roberta Frigerio; Demetrius M Maraganore Journal: Parkinsonism Relat Disord Date: 2014-03-05 Impact factor: 4.891
Authors: Yu-Hsuan Chuang; Ake T Lu; Kimberly C Paul; Aline D Folle; Jeff M Bronstein; Yvette Bordelon; Steve Horvath; Beate Ritz Journal: J Parkinsons Dis Date: 2019 Impact factor: 5.568
Authors: Jane M Maguire; Steve Bevan; Tara M Stanne; Erik Lorenzen; Israel Fernandez-Cadenas; Graeme J Hankey; Jordi Jimenez-Conde; Katarina Jood; Jin-Moo Lee; Robin Lemmens; Christopher Levi; Bo Norrving; Kristiina Rannikmae; Natalia Rost; Jonathan Rosand; Peter M Rothwell; Rodney Scott; Daniel Strbian; Jonathan Sturm; Cathie Sudlow; Matthew Traylor; Vincent Thijs; Turgut Tatlisumak; Tadeusz Wieloch; Daniel Woo; Bradford B Worrall; Christina Jern; Arne Lindgren Journal: Eur Stroke J Date: 2017-04-19
Authors: Yue Huang; Gang Wang; Dominic Rowe; Ying Wang; John B J Kwok; Qin Xiao; Frank Mastaglia; Jun Liu; Sheng-Di Chen; Glenda Halliday Journal: Biomed Res Int Date: 2015-04-15 Impact factor: 3.411
Authors: Sun Ju Chung; Joanna M Biernacka; Sebastian M Armasu; Kari Anderson; Roberta Frigerio; Jan O Aasly; Grazia Annesi; Anna Rita Bentivoglio; Laura Brighina; Marie-Christine Chartier-Harlin; Stefano Goldwurm; Georgios Hadjigeorgiou; Barbara Jasinska-Myga; Beom Seok Jeon; Yun Joong Kim; Rejko Krüger; Suzanne Lesage; Katerina Markopoulou; George Mellick; Karen E Morrison; Andreas Puschmann; Eng-King Tan; David Crosiers; Jessie Theuns; Christine Van Broeckhoven; Karin Wirdefeldt; Zbigniew K Wszolek; Alexis Elbaz; Demetrius M Maraganore Journal: Mov Disord Date: 2014-02-27 Impact factor: 10.338