Genomewide Association Studies of <scp><i>LRRK2</i></scp> Modifiers of Parkinson's Disease - Sorbonne Université Access content directly
Journal Articles Annals of Neurology Year : 2021

Genomewide Association Studies of LRRK2 Modifiers of Parkinson's Disease

Dongbing Lai
Babak Alipanahi
  • Function : Author
Pierre Fontanillas
  • Function : Author
Tae‐hwi Schwantes‐an
  • Function : Author
Jan Aasly
  • Function : Author
Roy N Alcalay
  • Function : Author
Gary W Beecham
  • Function : Author
Daniela Berg
  • Function : Author
Susan Bressman
  • Function : Author
Kathrin Brockman
Lorraine Clark
  • Function : Author
Mark Cookson
  • Function : Author
Sayantan Das
  • Function : Author
Vivianna van Deerlin
  • Function : Author
Jordan Follett
  • Function : Author
Matthew J Farrer
  • Function : Author
Joanne Trinh
  • Function : Author
Thomas Gasser
  • Function : Author
Stefano Goldwurm
  • Function : Author
Emil Gustavsson
  • Function : Author
Christine Klein
Anthony E Lang
  • Function : Author
J William Langston
  • Function : Author
Jeanne Latourelle
  • Function : Author
Timothy Lynch
  • Function : Author
Karen Marder
  • Function : Author
Connie Marras
  • Function : Author
Eden R Martin
  • Function : Author
Cory Y Mclean
  • Function : Author
Helen Mejia‐santana
  • Function : Author
Eric Molho
  • Function : Author
Richard H Myers
  • Function : Author
Karen Nuytemans
  • Function : Author
Laurie Ozelius
  • Function : Author
Haydeh Payami
  • Function : Author
Deborah Raymond
  • Function : Author
Ekaterina Rogaeva
  • Function : Author
Michael P Rogers
  • Function : Author
Owen A Ross
Ali Samii
  • Function : Author
Rachel Saunders‐pullman
  • Function : Author
Birgitt Schüle
  • Function : Author
Claudia Schulte
  • Function : Author
William K Scott
  • Function : Author
Caroline Tanner
  • Function : Author
Eduardo Tolosa
  • Function : Author
James E Tomkins
  • Function : Author
Dolores Vilas
  • Function : Author
John Q Trojanowski
  • Function : Author
Ryan Uitti
  • Function : Author
Jeffery M Vance
  • Function : Author
Naomi P Visanji
Zbigniew K Wszolek
  • Function : Author
Cyrus P Zabetian
Anat Mirelman
Nir Giladi
  • Function : Author
Avi Orr Urtreger
  • Function : Author
Paul Cannon
  • Function : Author
Brian Fiske
  • Function : Author
Tatiana Foroud
  • Function : Author

Abstract

Objective: The aim of this study was to search for genes/variants that modify the effect of LRRK2 mutations in terms of penetrance and age-at-onset of Parkinson’s disease. Methods: We performed the first genomewide association study of penetrance and age-at-onset of Parkinson’s dis- ease in LRRK2 mutation carriers (776 cases and 1,103 non-cases at their last evaluation). Cox proportional hazard models and linear mixed models were used to identify modifiers of penetrance and age-at-onset of LRRK2 mutations, respectively. We also investigated whether a polygenic risk score derived from a published genomewide association study of Parkinson’s disease was able to explain variability in penetrance and age-at-onset in LRRK2 mutation carriers. Results: A variant located in the intronic region of CORO1C on chromosome 12 (rs77395454; p value = 2.5E-08, beta = 1.27, SE = 0.23, risk allele: C) met genomewide significance for the penetrance model. Co-immunoprecipitation
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Dates and versions

hal-04538877 , version 1 (09-04-2024)

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Dongbing Lai, Babak Alipanahi, Pierre Fontanillas, Tae‐hwi Schwantes‐an, Jan Aasly, et al.. Genomewide Association Studies of LRRK2 Modifiers of Parkinson's Disease. Annals of Neurology, 2021, 90, pp.76 - 88. ⟨10.1002/ana.26094⟩. ⟨hal-04538877⟩
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