Huntington's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Huntington's Disease, including details on genetics, causes, symptoms, treatment. | ||||||||
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The relationship between CAG repeat length and age of onset differs for Huntington's disease patients with juvenile onset or adult onset.Andresen JM, Gayán J, Djoussé L, Roberts S, Brocklebank D, Cherny SS, , , Cardon LR, Gusella JF, MacDonald ME, Myers RH, Housman DE, Wexler NS Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139, USA. jma@mit.edu 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. Published 19 April 2007 in Ann Hum Genet, 71: 295-301.
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