Mitochondrial haplogroups and cognitive progression in Parkinson’s disease

International Genetics of Parkinson Disease Progression (IGPP) Consortium, Ganqiang Liu, Chunming Ni, Jiamin Zhan, Weimin Li, Junfeng Luo, Zhixiang Liao, Joseph J. Locascio, Wenbiao Xian, Ling Chen, Zhong Pei, Jean Christophe Corvol, Jodi Maple-Grødem, Meghan C. Campbell, Alexis Elbaz, Suzanne Lesage, Alexis Brice, Albert Y. Hung, Michael A. Schwarzschild, Michael T. HayesAnne Marie Wills, Bernard Ravina, Ira Shoulson, Pille Taba, Sulev Kõks, Thomas G. Beach, Florence Cormier-Dequaire, Guido Alves, Ole Bjørn Tysnes, Joel S. Perlmutter, Peter Heutink, Jacobus J. van Hilten, Roger A. Barker, Caroline H. Williams-Gray, Clemens R. Scherzer

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)42-49
Number of pages8
JournalBrain
Volume146
Issue number1
DOIs
StatePublished - Jan 1 2023

Keywords

  • Parkinson’s disease
  • cognitive progression
  • mitochondrial haplogroups

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