TY - JOUR
T1 - Mitochondrial haplogroups and cognitive progression in Parkinson’s disease
AU - International Genetics of Parkinson Disease Progression (IGPP) Consortium
AU - Liu, Ganqiang
AU - Ni, Chunming
AU - Zhan, Jiamin
AU - Li, Weimin
AU - Luo, Junfeng
AU - Liao, Zhixiang
AU - Locascio, Joseph J.
AU - Xian, Wenbiao
AU - Chen, Ling
AU - Pei, Zhong
AU - Corvol, Jean Christophe
AU - Maple-Grødem, Jodi
AU - Campbell, Meghan C.
AU - Elbaz, Alexis
AU - Lesage, Suzanne
AU - Brice, Alexis
AU - Hung, Albert Y.
AU - Schwarzschild, Michael A.
AU - Hayes, Michael T.
AU - Wills, Anne Marie
AU - Ravina, Bernard
AU - Shoulson, Ira
AU - Taba, Pille
AU - Köks, Sulev
AU - Beach, Thomas G.
AU - Cormier-Dequaire, Florence
AU - Alves, Guido
AU - Tysnes, Ole Bjørn
AU - Perlmutter, Joel S.
AU - Heutink, Peter
AU - van Hilten, Jacobus J.
AU - Barker, Roger A.
AU - Williams-Gray, Caroline H.
AU - Scherzer, Clemens R.
AU - Valentino, Rebecca R.
AU - Peng, Jiajie
AU - Liao, Zhixiang
AU - Locascio, Joseph J.
AU - Corvol, Jean Christophe
AU - Dong, Xianjun
AU - Maple-Grødem, Jodi
AU - Campbell, Meghan C.
AU - Elbaz, Alexis
AU - Lesage, Suzanne
AU - Brice, Alexis
AU - Mangone, Graziella
AU - Growdon, John H.
AU - Hung, Albert Y.
AU - Kasten, Meike
AU - Klein, Christine
N1 - Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - Mitochondria are a culprit in the onset of Parkinson’s disease, but their role during disease progression is unclear. Here we used Cox proportional hazards models to exam the effect of variation in the mitochondrial genome on longitudinal cognitive and motor progression over time in 4064 patients with Parkinson’s disease. Mitochondrial macro-haplogroup was associated with reduced risk of cognitive disease progression in the discovery and replication population. In the combined analysis, patients with the super macro-haplogroup J, T, U# had a 41% lower risk of cognitive progression with P= 2.42 × 10−6 compared to those with macro-haplogroup H. Exploratory analysis indicated that the common mitochondrial DNA variant, m.2706A>G, was associated with slower cognitive decline with a hazard ratio of 0.68 (95% confidence interval 0.56–0.81) and P= 2.46 × 10−5. Mitochondrial haplogroups were not appreciably linked to motor progression. This initial genetic survival study of the mitochondrial genome suggests that mitochondrial haplogroups may be associated with the pace of cognitive progression in Parkinson’s disease over time.
AB - Mitochondria are a culprit in the onset of Parkinson’s disease, but their role during disease progression is unclear. Here we used Cox proportional hazards models to exam the effect of variation in the mitochondrial genome on longitudinal cognitive and motor progression over time in 4064 patients with Parkinson’s disease. Mitochondrial macro-haplogroup was associated with reduced risk of cognitive disease progression in the discovery and replication population. In the combined analysis, patients with the super macro-haplogroup J, T, U# had a 41% lower risk of cognitive progression with P= 2.42 × 10−6 compared to those with macro-haplogroup H. Exploratory analysis indicated that the common mitochondrial DNA variant, m.2706A>G, was associated with slower cognitive decline with a hazard ratio of 0.68 (95% confidence interval 0.56–0.81) and P= 2.46 × 10−5. Mitochondrial haplogroups were not appreciably linked to motor progression. This initial genetic survival study of the mitochondrial genome suggests that mitochondrial haplogroups may be associated with the pace of cognitive progression in Parkinson’s disease over time.
UR - http://www.scopus.com/inward/record.url?scp=85145955251&partnerID=8YFLogxK
U2 - 10.1093/brain/awac327
DO - 10.1093/brain/awac327
M3 - Journal articles
C2 - 36343661
AN - SCOPUS:85145955251
SN - 0006-8950
VL - 146
SP - 42
EP - 49
JO - Brain
JF - Brain
IS - 1
ER -
