Full sequencing and haplotype analysis of MAPT in Parkinson's disease and rapid eye movement sleep behavior disorder

Jiao Li, Jennifer A Ruskey, Isabelle Arnulf, Yves Dauvilliers, Michele T M Hu, Birgit Högl, Claire S Leblond, Sirui Zhou, Amirthagowri Ambalavanan, Jay P Ross, Cynthia V Bourassa, Dan Spiegelman, Sandra B Laurent, Ambra Stefani, Christelle Charley Monaca, Valérie Cochen De Cock, Michel Boivin, Luigi Ferini-Strambi, Giuseppe Plazzi, Elena AntelmiPeter Young, Anna Heidbreder, Catherine Labbe, Tanis J Ferman, Patrick A Dion, Dongsheng Fan, Alex Desautels, Jean-François Gagnon, Nicolas Dupré, Edward A Fon, Jacques Y Montplaisir, Bradley F Boeve, Ronald B Postuma, Guy A Rouleau, Owen A Ross, Ziv Gan-Or

Research output: Contribution to journalArticle

Abstract

BACKGROUND: MAPT haplotypes are associated with PD, but their association with rapid eye movement sleep behavior disorder is unclear.

OBJECTIVE: To study the role of MAPT variants in rapid eye movement sleep behavior disorder.

METHODS: Two cohorts were included: (A) PD (n = 600), rapid eye movement sleep behavior disorder (n = 613) patients, and controls (n = 981); (B) dementia with Lewy bodies patients with rapid eye movement sleep behavior disorder (n = 271) and controls (n = 950). MAPT-associated variants and the entire coding sequence of MAPT were analyzed. Age-, sex-, and ethnicity-adjusted analyses were performed to examine the association between MAPT, PD, and rapid eye movement sleep behavior disorder.

RESULTS: MAPT-H2 variants were associated with PD (odds ratios: 0.62-0.65; P = 0.010-0.019), but not with rapid eye movement sleep behavior disorder. In PD, the H1 haplotype odds ratio was 1.60 (95% confidence interval: 1.12-2.28; P = 0.009), and the H2 odds ratio was 0.68 (95% confidence interval: 0.48-0.96; P = 0.03). The H2/H1 haplotypes were not associated with rapid eye movement sleep behavior disorder.

CONCLUSIONS: Our results confirm the protective effect of the MAPT-H2 haplotype in PD, and define its components. Furthermore, our results suggest that MAPT does not play a major role in rapid eye movement sleep behavior disorder, emphasizing different genetic background than in PD in this locus. © 2018 International Parkinson and Movement Disorder Society.

Original languageEnglish
JournalMovement Disorders
DOIs
Publication statusPublished - 2018

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Li, J., Ruskey, J. A., Arnulf, I., Dauvilliers, Y., Hu, M. T. M., Högl, B., Leblond, C. S., Zhou, S., Ambalavanan, A., Ross, J. P., Bourassa, C. V., Spiegelman, D., Laurent, S. B., Stefani, A., Charley Monaca, C., Cochen De Cock, V., Boivin, M., Ferini-Strambi, L., Plazzi, G., ... Gan-Or, Z. (2018). Full sequencing and haplotype analysis of MAPT in Parkinson's disease and rapid eye movement sleep behavior disorder. Movement Disorders. https://doi.org/10.1002/mds.27385