Journal article
The relationship between CAG repeat length and age of onset differs for Huntington's disease patients with juvenile onset or adult onset
Annals of human genetics, Vol.71(3), pp.295-301
05/2007
DOI: 10.1111/j.1469-1809.2006.00335.x
PMID: 17181545
Abstract
Age of onset for Huntington's disease (HD) varies inversely with the length of the disease-causing CAG repeat expansion in the HD gene. A simple exponential regression model yielded adjusted R-squared values of 0.728 in a large set of Venezuelan kindreds and 0.642 in a North American, European, and Australian sample (the HD MAPS cohort). We present evidence that a two-segment exponential regression curve provides a significantly better fit than the simple exponential regression. A plot of natural log-transformed age of onset against CAG repeat length reveals this segmental relationship. This two-segment exponential regression on age of onset data increases the adjusted R-squared values by 0.012 in the Venezuelan kindreds and by 0.035 in the HD MAPS cohort. Although the amount of additional variance explained by the segmental regression approach is modest, the two slopes of the two-segment regression are significantly different from each other in both the Venezuelan kindreds [F(2, 439) = 11.13, P = 2 x 10(-5)] and in the HD MAPS cohort [F(2, 688) = 38.27, P = 2 x 10(-16)]. In both populations, the influence of each CAG repeat on age of onset appears to be stronger in the adult-onset range of CAG repeats than in the juvenile-onset range.
Details
- Title: Subtitle
- The relationship between CAG repeat length and age of onset differs for Huntington's disease patients with juvenile onset or adult onset
- Creators
- J. Michael Andresen - Massachusetts Institute of TechnologyJavier Gayan - University of OxfordLuc Djousse - Boston UniversitySimone Roberts - Columbia UniversityDenise Brocklebank - University of OxfordStacey S. Cherny - University of Hong KongLon R. Cardon - University of OxfordJames F. Gusella - Harvard UniversityMarcy E. MacDonald - Harvard UniversityRichard H. MyersDavid E. Housman - Massachusetts Institute of TechnologyNancy S. Wexler - Columbia UniversityHD MAPS Collaborative Research Group
- Contributors
- Jane S Paulsen (Contributor) - University of Iowa, Psychological and Brain Sciences
- Resource Type
- Journal article
- Publication Details
- Annals of human genetics, Vol.71(3), pp.295-301
- Publisher
- Wiley
- DOI
- 10.1111/j.1469-1809.2006.00335.x
- PMID
- 17181545
- ISSN
- 0003-4800
- eISSN
- 1469-1809
- Number of pages
- 7
- Grant note
- NS16367; P50 NS016367; R01 NS032765; NS32765 / NINDS NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) Wellcome Trust; European Commission P01NS016367 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Language
- English
- Date published
- 05/2007
- Academic Unit
- Psychiatry; Psychological and Brain Sciences
- Record Identifier
- 9984383310002771
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