Genetic modifiers of Huntington disease differentially influence motor and cognitive domains

• Published in: American journal of human genetics Vol. 109; no. 5; pp. 885 - 899
• Main Authors: Lee, Jong-Min, Huang, Yuan, Orth, Michael, Gillis, Tammy, Siciliano, Jacqueline, Hong, Eunpyo, Mysore, Jayalakshmi Srinidhi, Lucente, Diane, Wheeler, Vanessa C., Seong, Ihn Sik, McLean, Zachariah L., Mills, James A., McAllister, Branduff, Lobanov, Sergey V., Massey, Thomas H., Ciosi, Marc, Landwehrmeyer, G. Bernhard, Paulsen, Jane S., Dorsey, E. Ray, Shoulson, Ira, Sampaio, Cristina, Monckton, Darren G., Kwak, Seung, Holmans, Peter, Jones, Lesley, MacDonald, Marcy E., Long, Jeffrey D., Gusella, James F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.05.2022; Elsevier
• Subjects: age at onset; CAG repeat; Cognition; disease modification; DNA; DNA maintenance; DNA repair; genetic modifier; Genome-Wide Association Study; Humans; Huntingtin Protein - genetics; Huntington disease; Huntington Disease - genetics; Huntington Disease - pathology; polyglutamine disease; somatic expansion; trinucleotide repeat; Trinucleotide Repeat Expansion; somatic expansion; Huntington disease; DNA maintenance; trinucleotide repeat; CAG repeat; age at onset; DNA repair; genetic modifier; polyglutamine disease; disease modification

Genome-wide association studies (GWASs) of Huntington disease (HD) have identified six DNA maintenance gene loci (among others) as modifiers and implicated a two step-mechanism of pathogenesis: somatic instability of the causative HTT CAG repeat with subsequent triggering of neuronal damage. The lar...